Clinical Issues in Emergency Contraception James Trussell, PhD.
Oral emergency contraception: an efficacy · Describe the recent changes in levonorgestrel (LNG) EC...
79
Oral emergency contraception: an efficacy and regulatory update Rebecca Stone, PharmD, BCPS, BCACP Marlowe Djuric Kachlic, PharmD University of Illinois at Chicago College of Pharmacy UI Hospital and Health Sciences System (UIHHS)
Transcript of Oral emergency contraception: an efficacy · Describe the recent changes in levonorgestrel (LNG) EC...
Oral emergency contraception an efficacy
and regulatory updateRebecca Stone PharmD BCPS BCACP
Marlowe Djuric Kachlic PharmD
University of Illinois at Chicago College of Pharmacy
UI Hospital and Health Sciences System (UIHHS)
DisclosuresConflict of Interest
bull The speakers declare no conflicts of interest real or apparent and no financial interests in any company product or service mentioned in this program including grants employment gifts stock holdings and honoraria
ObjectivesPharmacists
bull Explain the mechanism of action for available oral emergency contraception (EC) products as supported by current research
bull Describe the recent changes in levonorgestrel (LNG) EC labeling in the international setting and implications in the US
bull Interpret the evidence available regarding oral EC efficacy including LNG and ulipristal acetate (UPA)
bull Explain the legal regulations surrounding patient purchase of oral LNG EC and UPA EC and recommend appropriate EC for a patient
At the conclusion of this program the pharmacist will be able to
ObjectivesPharmacy Technicians
bull Describe the appropriate time period for patients to utilize oral EC methods
bull Explain the legal regulations surrounding patient purchase of oral LNG EC and UPA EC
bull Describe where different types of EC products may be stocked in the pharmacy
At the conclusion of this program the pharmacy technician will be able to
BACKGROUND
Unintended pregnancy in the United States
Intended Pregnancy
51
Birth 22
Abortion 20
Miscarriage 7
Unintended Pregnancy
49
67 million pregnancies
Finer et al Contraception 2011
Physiology definitions
bull Ovulation
bull Lutenizing hormone (LH) increases and triggers the release of an oocyte (egg) from the ovary
bull Pregnancy
bull Zygote (fertilized egg) successfully implants into the endometrium (uterine lining)
Conception
bull Sperm must fertilize oocyte within 24 hours of ovulation
bull Oocyte survival is 24 hrs
bull Sperm can survive in the female reproductive tract for 5 days
bull Fertile window
bull 5 days before ovulation to 1 day after
Gemzell-Danielsson K Contraception 2013 Trussell J Contraception 1998 Wilcox AJ NEJM 1995 Wilcox AJ Hum Reprod 2004
Probability of conception on specific days near the day of ovulation
Wilcox AJ N Engl J Med 1995
Ovulation
Conception
bull Assessing time of ovulation is difficult
bull Discrepancy
bull Patient reported stage of menstrual cycle
bull Dating based on endocrine data
bull Unprotected intercourse outside of the supposed fertile period may still result in pregnancy
Gemzell-Danielsson et al Contraception 2013 Novikova et al Contraception 2007 Wilcox et al BMJ 2000
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
DisclosuresConflict of Interest
bull The speakers declare no conflicts of interest real or apparent and no financial interests in any company product or service mentioned in this program including grants employment gifts stock holdings and honoraria
ObjectivesPharmacists
bull Explain the mechanism of action for available oral emergency contraception (EC) products as supported by current research
bull Describe the recent changes in levonorgestrel (LNG) EC labeling in the international setting and implications in the US
bull Interpret the evidence available regarding oral EC efficacy including LNG and ulipristal acetate (UPA)
bull Explain the legal regulations surrounding patient purchase of oral LNG EC and UPA EC and recommend appropriate EC for a patient
At the conclusion of this program the pharmacist will be able to
ObjectivesPharmacy Technicians
bull Describe the appropriate time period for patients to utilize oral EC methods
bull Explain the legal regulations surrounding patient purchase of oral LNG EC and UPA EC
bull Describe where different types of EC products may be stocked in the pharmacy
At the conclusion of this program the pharmacy technician will be able to
BACKGROUND
Unintended pregnancy in the United States
Intended Pregnancy
51
Birth 22
Abortion 20
Miscarriage 7
Unintended Pregnancy
49
67 million pregnancies
Finer et al Contraception 2011
Physiology definitions
bull Ovulation
bull Lutenizing hormone (LH) increases and triggers the release of an oocyte (egg) from the ovary
bull Pregnancy
bull Zygote (fertilized egg) successfully implants into the endometrium (uterine lining)
Conception
bull Sperm must fertilize oocyte within 24 hours of ovulation
bull Oocyte survival is 24 hrs
bull Sperm can survive in the female reproductive tract for 5 days
bull Fertile window
bull 5 days before ovulation to 1 day after
Gemzell-Danielsson K Contraception 2013 Trussell J Contraception 1998 Wilcox AJ NEJM 1995 Wilcox AJ Hum Reprod 2004
Probability of conception on specific days near the day of ovulation
Wilcox AJ N Engl J Med 1995
Ovulation
Conception
bull Assessing time of ovulation is difficult
bull Discrepancy
bull Patient reported stage of menstrual cycle
bull Dating based on endocrine data
bull Unprotected intercourse outside of the supposed fertile period may still result in pregnancy
Gemzell-Danielsson et al Contraception 2013 Novikova et al Contraception 2007 Wilcox et al BMJ 2000
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
ObjectivesPharmacists
bull Explain the mechanism of action for available oral emergency contraception (EC) products as supported by current research
bull Describe the recent changes in levonorgestrel (LNG) EC labeling in the international setting and implications in the US
bull Interpret the evidence available regarding oral EC efficacy including LNG and ulipristal acetate (UPA)
bull Explain the legal regulations surrounding patient purchase of oral LNG EC and UPA EC and recommend appropriate EC for a patient
At the conclusion of this program the pharmacist will be able to
ObjectivesPharmacy Technicians
bull Describe the appropriate time period for patients to utilize oral EC methods
bull Explain the legal regulations surrounding patient purchase of oral LNG EC and UPA EC
bull Describe where different types of EC products may be stocked in the pharmacy
At the conclusion of this program the pharmacy technician will be able to
BACKGROUND
Unintended pregnancy in the United States
Intended Pregnancy
51
Birth 22
Abortion 20
Miscarriage 7
Unintended Pregnancy
49
67 million pregnancies
Finer et al Contraception 2011
Physiology definitions
bull Ovulation
bull Lutenizing hormone (LH) increases and triggers the release of an oocyte (egg) from the ovary
bull Pregnancy
bull Zygote (fertilized egg) successfully implants into the endometrium (uterine lining)
Conception
bull Sperm must fertilize oocyte within 24 hours of ovulation
bull Oocyte survival is 24 hrs
bull Sperm can survive in the female reproductive tract for 5 days
bull Fertile window
bull 5 days before ovulation to 1 day after
Gemzell-Danielsson K Contraception 2013 Trussell J Contraception 1998 Wilcox AJ NEJM 1995 Wilcox AJ Hum Reprod 2004
Probability of conception on specific days near the day of ovulation
Wilcox AJ N Engl J Med 1995
Ovulation
Conception
bull Assessing time of ovulation is difficult
bull Discrepancy
bull Patient reported stage of menstrual cycle
bull Dating based on endocrine data
bull Unprotected intercourse outside of the supposed fertile period may still result in pregnancy
Gemzell-Danielsson et al Contraception 2013 Novikova et al Contraception 2007 Wilcox et al BMJ 2000
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
ObjectivesPharmacy Technicians
bull Describe the appropriate time period for patients to utilize oral EC methods
bull Explain the legal regulations surrounding patient purchase of oral LNG EC and UPA EC
bull Describe where different types of EC products may be stocked in the pharmacy
At the conclusion of this program the pharmacy technician will be able to
BACKGROUND
Unintended pregnancy in the United States
Intended Pregnancy
51
Birth 22
Abortion 20
Miscarriage 7
Unintended Pregnancy
49
67 million pregnancies
Finer et al Contraception 2011
Physiology definitions
bull Ovulation
bull Lutenizing hormone (LH) increases and triggers the release of an oocyte (egg) from the ovary
bull Pregnancy
bull Zygote (fertilized egg) successfully implants into the endometrium (uterine lining)
Conception
bull Sperm must fertilize oocyte within 24 hours of ovulation
bull Oocyte survival is 24 hrs
bull Sperm can survive in the female reproductive tract for 5 days
bull Fertile window
bull 5 days before ovulation to 1 day after
Gemzell-Danielsson K Contraception 2013 Trussell J Contraception 1998 Wilcox AJ NEJM 1995 Wilcox AJ Hum Reprod 2004
Probability of conception on specific days near the day of ovulation
Wilcox AJ N Engl J Med 1995
Ovulation
Conception
bull Assessing time of ovulation is difficult
bull Discrepancy
bull Patient reported stage of menstrual cycle
bull Dating based on endocrine data
bull Unprotected intercourse outside of the supposed fertile period may still result in pregnancy
Gemzell-Danielsson et al Contraception 2013 Novikova et al Contraception 2007 Wilcox et al BMJ 2000
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
BACKGROUND
Unintended pregnancy in the United States
Intended Pregnancy
51
Birth 22
Abortion 20
Miscarriage 7
Unintended Pregnancy
49
67 million pregnancies
Finer et al Contraception 2011
Physiology definitions
bull Ovulation
bull Lutenizing hormone (LH) increases and triggers the release of an oocyte (egg) from the ovary
bull Pregnancy
bull Zygote (fertilized egg) successfully implants into the endometrium (uterine lining)
Conception
bull Sperm must fertilize oocyte within 24 hours of ovulation
bull Oocyte survival is 24 hrs
bull Sperm can survive in the female reproductive tract for 5 days
bull Fertile window
bull 5 days before ovulation to 1 day after
Gemzell-Danielsson K Contraception 2013 Trussell J Contraception 1998 Wilcox AJ NEJM 1995 Wilcox AJ Hum Reprod 2004
Probability of conception on specific days near the day of ovulation
Wilcox AJ N Engl J Med 1995
Ovulation
Conception
bull Assessing time of ovulation is difficult
bull Discrepancy
bull Patient reported stage of menstrual cycle
bull Dating based on endocrine data
bull Unprotected intercourse outside of the supposed fertile period may still result in pregnancy
Gemzell-Danielsson et al Contraception 2013 Novikova et al Contraception 2007 Wilcox et al BMJ 2000
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Unintended pregnancy in the United States
Intended Pregnancy
51
Birth 22
Abortion 20
Miscarriage 7
Unintended Pregnancy
49
67 million pregnancies
Finer et al Contraception 2011
Physiology definitions
bull Ovulation
bull Lutenizing hormone (LH) increases and triggers the release of an oocyte (egg) from the ovary
bull Pregnancy
bull Zygote (fertilized egg) successfully implants into the endometrium (uterine lining)
Conception
bull Sperm must fertilize oocyte within 24 hours of ovulation
bull Oocyte survival is 24 hrs
bull Sperm can survive in the female reproductive tract for 5 days
bull Fertile window
bull 5 days before ovulation to 1 day after
Gemzell-Danielsson K Contraception 2013 Trussell J Contraception 1998 Wilcox AJ NEJM 1995 Wilcox AJ Hum Reprod 2004
Probability of conception on specific days near the day of ovulation
Wilcox AJ N Engl J Med 1995
Ovulation
Conception
bull Assessing time of ovulation is difficult
bull Discrepancy
bull Patient reported stage of menstrual cycle
bull Dating based on endocrine data
bull Unprotected intercourse outside of the supposed fertile period may still result in pregnancy
Gemzell-Danielsson et al Contraception 2013 Novikova et al Contraception 2007 Wilcox et al BMJ 2000
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Physiology definitions
bull Ovulation
bull Lutenizing hormone (LH) increases and triggers the release of an oocyte (egg) from the ovary
bull Pregnancy
bull Zygote (fertilized egg) successfully implants into the endometrium (uterine lining)
Conception
bull Sperm must fertilize oocyte within 24 hours of ovulation
bull Oocyte survival is 24 hrs
bull Sperm can survive in the female reproductive tract for 5 days
bull Fertile window
bull 5 days before ovulation to 1 day after
Gemzell-Danielsson K Contraception 2013 Trussell J Contraception 1998 Wilcox AJ NEJM 1995 Wilcox AJ Hum Reprod 2004
Probability of conception on specific days near the day of ovulation
Wilcox AJ N Engl J Med 1995
Ovulation
Conception
bull Assessing time of ovulation is difficult
bull Discrepancy
bull Patient reported stage of menstrual cycle
bull Dating based on endocrine data
bull Unprotected intercourse outside of the supposed fertile period may still result in pregnancy
Gemzell-Danielsson et al Contraception 2013 Novikova et al Contraception 2007 Wilcox et al BMJ 2000
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Conception
bull Sperm must fertilize oocyte within 24 hours of ovulation
bull Oocyte survival is 24 hrs
bull Sperm can survive in the female reproductive tract for 5 days
bull Fertile window
bull 5 days before ovulation to 1 day after
Gemzell-Danielsson K Contraception 2013 Trussell J Contraception 1998 Wilcox AJ NEJM 1995 Wilcox AJ Hum Reprod 2004
Probability of conception on specific days near the day of ovulation
Wilcox AJ N Engl J Med 1995
Ovulation
Conception
bull Assessing time of ovulation is difficult
bull Discrepancy
bull Patient reported stage of menstrual cycle
bull Dating based on endocrine data
bull Unprotected intercourse outside of the supposed fertile period may still result in pregnancy
Gemzell-Danielsson et al Contraception 2013 Novikova et al Contraception 2007 Wilcox et al BMJ 2000
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Probability of conception on specific days near the day of ovulation
Wilcox AJ N Engl J Med 1995
Ovulation
Conception
bull Assessing time of ovulation is difficult
bull Discrepancy
bull Patient reported stage of menstrual cycle
bull Dating based on endocrine data
bull Unprotected intercourse outside of the supposed fertile period may still result in pregnancy
Gemzell-Danielsson et al Contraception 2013 Novikova et al Contraception 2007 Wilcox et al BMJ 2000
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Conception
bull Assessing time of ovulation is difficult
bull Discrepancy
bull Patient reported stage of menstrual cycle
bull Dating based on endocrine data
bull Unprotected intercourse outside of the supposed fertile period may still result in pregnancy
Gemzell-Danielsson et al Contraception 2013 Novikova et al Contraception 2007 Wilcox et al BMJ 2000
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Probability of clinical pregnancy with one act of intercourse relative to day of the menstrual cycle
Wilcox AJ Contraception 2001
EC should be administered regardless of cycle day to prevent an
unwanted pregnancy
Ovulation1st day of menses
Allen et al Contraception 2001
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Conception probability
Days prior to Ovulation
Probability of Conception
5 36
4 136
3 155
2 277
1 298
0 123
bull Overall pregnancy rate expected in absence of EC is 56
bull FDA and European Medicines Agency (EMA) established a pregnancy rate of lt 4 as the EC efficacy benchmark
Glasier A Contraception 2011 Trussell J Contraception 1998 Wilcox AJ NEJM 1995
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Percentage of sexually experienced women aged 15-44 who have ever used emergency contraception
0
2
4
6
8
10
12
1995 2002 2006-2010
Percentage ever used
Daniels et al NCHS Data Brief 2013
59
24
17
0
20
40
60
80
100
2006-2010
Frequency of use
Threeor more
Twice
Once
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
EMERGENCY CONTRACEPTIVE AGENTS
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
EC products in the US
UPA EC LNG ECCopper-T IUD
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Copper-T IUD
bull Paragardreg
bull Placed within 5 days after intercourse
bull Efficacy
bull Most effective method
bull Effectiveness does not decline with delay
bull Failure rate lt 1
bull Prescription only
Trussell 2011 httpecprincetoneduquestionsec-reviewpdf
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Copper-T IUD MOA
bull Enhances the inflammatory response reaching levels that are toxic for sperm
bull Diminishes sperm penetration impairs motility
bull Emergency contraception is off label use
bull Placed by trained clinician
bull More barriers to access
bull Provides long term contraception
Gemzell-Danielsson et al Contraception 2013 Ortiz et al Obstet Gynecol Surv 1996 Roblero et al Reprod Fertil Dev 1996
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
UPA EC
bull Ellareg
bull Dose
bull 30 mg x 1 dose
bull Administration
bull Take within 5 days after intercourse
bull Efficacy
bull Approved for a longer window than LNG EC
bull More effective than LNG EC
bull Prescription only
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
UPA EC MOA
bull 2nd generation selective progesterone receptor modulator
bull No effect on sperm function
bull Direct inhibitory effect on follicular rupture
bull Decreased efficacy but may still work even when luteinizing hormone (LH) has started to rise
bull Likely does not effect embryo implantation
Gemzell-Danielsson et al Contraception 2013 Brache et al Hum Reprod 2010
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
LNG EC
bull Levonorgestrel
bull Dose
bull 075 mg x 2 doses
bull 15 mg x 1 dose
bull Administration
bull Take within 72 hours after intercourse
bull Off label ndash may take up to 5 days after intercourse
bull OTC BTC amp prescription
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
LNG EC MOA
bull Progestin
bull No effect on sperm function
bull Affects follicular development after dominant follicle selection
bull ONLY before rise in LH
bull No effect on embryo implantation
Gemzell-Danielsson K Contraception 2013
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
0
10
20
30
40
50
60
70
Control Levonorgestrel Mifepristone
Pe
rce
nt
of
em
bry
o a
tta
che
d
Treatment Groups
In vitro model for human embryo implantation
Gemzell-Danielsson K Contraception 2013 Lalitkumar PGL Hum Reprod 2007
1017614 015
No significant difference
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
EC adverse events
Glasier et al Lancet 2010
Glasier et al LNG vs UPA EC
0020406080
100120140160180200
UPA (n=1104)
LNG (n=1117)
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
LNG amp UPA EC EFFICACY
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Clinical trial meta-analysis
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Limited UPA data
Abitbol JL ASEC Webinar May 2014 Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
UPA Published Studies
LNG vs UPA RCTs
Crenin et al 2006UPA
7773 pregnancies091
Glasier et al 2010UPA
15941 pregnancies159
Fine et al 2010UPA
261241 pregnancies210
Observational
LNG 13773 pregnancies
17
LNG25958 pregnancies
26
LNG comparatorsn = 1731
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Clinical trial design
Crenin et al 2006 Glasier et al 2010
N = 1546 N = 1899
UPA = 773 LNG = 773 UPA = 941 LNG = 958
UPA Phase II trial UPA Phase III trial
Received EC within 72 hr Received EC within 120 hr
075 mg x 2 doses 15 mg x 1 dose
Weight measured Weight self reported
Glasier A Lancet 2010 Creinin MD Obstet Gynecol 2006
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
EFFICACY AND BODY WEIGHT
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Pregnancy risk according to BMI
11 11
26
13
25
58
00
10
20
30
40
50
60
70
lt25 25-30 gt30
Pe
rce
nt
pre
gn
an
t
BMI
UPA LNG
Glasier A Contraception 2011
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Kapp et al Contraception 2015
Pregnancy rate following LNG EC according to weight categories
Weight (kg) lt 55 55-65 65-75 75-85 ge85
N total 349 608 426 155 193
N pregnancies 3 8 6 10 11
Pregnancy rate 09 13 14 64 57
95 Confidence interval
02-25 06-26 05-30 31-11529-100
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
LNG EC pregnancy probability by weight
Kapp et al Contraception 2015
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Clinical trial limitations
bull Exploratory analyses
bull Neither trial designed to evaluate the effect of weight on the effectiveness of EC
bull Weight was self reported in Glasier et al 2010
bull ~55 of patients
bull Limited number of pregnancies (n=38)
bull BMI of 30 or greater (n=242)
bull Pregnancies with BMI of 35 or greater ldquoextremely smallrdquo
Glasier A Contraception 2011
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
LNG EC European labeling
bull NorLevo label was changed in Europe amp Canada in late 2013
bull ldquoIn clinical trials contraceptive efficacy was reduced in women weighing 75 kg or more and LNG was not effective in women who weighed more than 80 kgrdquo
bull NorLevoreg distributor
bull HRA Pharma
bull Distributes product to over 50 countries
bull Sole manufacturer of UPA
Norlevo Package Insert 2013
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Previous clinical trial data
bull Effect not reported in previous studies
bull Mean body weight much lower
bull Different demographics
bull Predominantly Asian and African population
Von Hertzen H Lancet 1998 Von Hertzen H Lancet 2002 Dada O Contraception 2010
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Previous published trial data
Clinical Trial Trial designLNG EC
demographic dataLNG EC
pregnancy rate
Von Hertzen et alLancet1998
bull LNG vs Yuzpe methodbull EC taken le 72 hrsbull 21 study sites
n = 976Mean BMI 220
1197611
Von Hertzen et alLancet 2002
bull Mifepristone vs LNG 1 dose vs LNG 2 dose
bull EC taken le 120 hrsbull 15 study sites
n = 2712Mean weight 562
kg
442712162
Dada et alContraception2010
bull LNG 1 dose vs LNG 2 dosebull EC taken le 120 hrsbull 7 sites (all Nigeria)
n = 2823Mean BMI 242
172823061
LNG comparators n = 6511
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Data implementation
bull European Medicines Agency 72014
bull ldquoLNG EC can continue to be used in women of all weights as the benefits are considered to outweigh the risksrdquo
bull EMA reviewed three WHO trials and stated they did not find reduced efficacy with increasing weight or BMI
bull Statement was removed from the label
bull FDA continues to review available data
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Cause of weight related decrease in LNG efficacy
bull Unknown if efficacy is decreased by metabolic or pharmacokinetic changes
bull No data evaluating higher doses of LNG
bull Decreased efficacy with other hormonals
bull Contraceptive patch (90 kg warning)
bull Combined oral contraceptives
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 1
LNG EC may be less effective in women weighing more than 165 lbs
a True
b False
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
REGIMEN TIMING AND EFFICACY
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Timing and Efficacy
bull Always give EC as soon as possible
bull When stratified by time UPA was found to have lower failure rates than LNG
bull odds ratio for pregnancy 65 lower in the first 24 hours
bull odds ratio for pregnancy 42 lower up to 72 hours
bull odds ratio for pregnancy45 lower up to 120 hours
Glasier et al Lancet 2010
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Timing and efficacy
bull Related to MOA
bull When ovulation is imminent UPA is more effective than LNG in delaying it if administered within 5 days
bull If the follicle reaches 15ndash17 mm LNG is not able to prevent follicular rupture better than placebo
bull If the leading follicle reaches 18ndash20 mm UPA prevents follicular rupture in 59 of cycles compared with 0 in placebo cycles
Croxatto et al Contraception 2004 Brache et al Hum Reprod 2010
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Repeated acts of intercourse following EC use
bull Repeated acts of intercourse following EC use increase the likelihood of pregnancy with both LNG and UPA EC
bull Women should use back up with progestin containing contraceptives following use of Ella
bull Mechanism may render them ineffective
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 2
LNG EC can be effective if taken up to 5 days after unprotected intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 3
LNG EC is more effective than UPA EC when taken on day 5 following intercourse
a True
b False
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
WHAT IS THE NEXT STEP
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Efficacy summary
bull Efficacy declines over time for all oral EC
bull Women are not able to reliably assess how close they are to ovulation
bull ldquoIs LNG today more effective than UPA tomorrowrdquo
bull Currently there is no data to gauge the efficacy impact of delaying EC in order to obtain UPA
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Planned Parenthood
httpwwwplannedparenthoodorghealth-center Accessed 622014
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
My perspective
bull Risk vs benefit of EC types should be discussed at well woman visits
bull Ellareg script should be provided in advance
bull Copper IUD is the most effective type of EC
bull When using oral EC ellareg should be first choice
bull However do not significantly delay EC administration
bull LNG EC is better than no EC
bull In absence of conclusive studies provide information about potential relationship between weight and efficacy
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
LEGAL AND REGULATORY INFORMATION
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
History of EC dispensing in Illinois
bull In 2005 former governor Blagojevich signed emergency rule which required pharmacists to dispense EC with a valid prescription without delay
bull Pharmacists could be fined or lose their license if they refused to fill
bull Challenged by 2 pharmacists citing the Conscience Act and the Freedom of Religion Act
ldquoEmergency Contraception Law and Ethicsrdquo httpwwwuspharmacistcomcontentdpharmacy_lawc37747ldquoBeyond the Issue of Pharmacist Refusals Pharmacies that Wonrsquot Sell Emergency Contraceptionrdquo httpwwwguttmacherorgpubstgr083gr080310html
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
History of EC dispensing in Illinois
bull In 2009 the circuit court granted an injunction to the pharmacists prohibiting the state from enforcing the law
bull The rule was amended in April 2010 stating pharmacies had a ldquoduty to deliver lawfully prescribed drugs to patients and distribute nonprescription drugsrdquo
bull EC not mentioned neither was conscience- or religious-based objections
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Pharmacy organization stance
bull APhA
bull Added a conscience clause to the Code of Ethics in 1998
bull ACCP
bull Position statement in 2005
bull Both recognize that a pharmacist has the right to conscientiously refuse to dispense certain medications but encourages that policies be developed to ensure medication delivery to the patient in a timely manner
ldquoPrerogative of a Pharmacist to Decline to Provide Professional Services Based on Consciencerdquo httpwwwaccpcomdocspositionspositionStatementspos31_200508pdf
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
ldquoState Policies in Brief Emergency Contraceptionrdquo httpwwwguttmacherorgstatecenterspibsspib_ECpdf
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Laws surrounding EC dispensing
bull Pharmacies must fill valid prescriptions for EC
bull Unless they refuse
bull Illinois law allows for refusal to dispense EC by pharmacists and pharmacies
bull Broadly worded--refusal may apply to either but does not specifically include them
60
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
A brief legal history of LNG
bull May 1999 ndash Plan B approved as Rx drug by FDA
bull August 2006 ndash Plan B approved as OTC for consumers 18 and older (Rx for 17 and younger)
bull April 2009 ndash Plan B approved for sale OTC to women and men 17 and older
bull December 2011 ndash FDA was to approve Plan B with no age restrictionmdashoverruled by HHS Secretary Kathleen Sebelius
ldquoHistory of Plan B OTCrdquo httpecprincetonedupillsplanbhistoryhtmlldquoThe Fight for Emergency Contraception Every Second Countsrdquo httpreproductiverightsorgenprint1133
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
A brief legal history of LNG
bull 2012 ndash Teva files amended application to the FDA to make Plan B One Step available OTC to consumers 15 and over and not BTC
bull April 2013 ndash Amendment approved by FDA
bull June 2013 ndash Plan B One Step approved by FDA for unrestricted sale OTC
bull February 2014 ndash FDA approves generic one-pill EC products for unrestricted sale OTC
FDA Orange Book httpwwwaccessdatafdagovscriptscderobdocsobdetailcfmAppl_No=021998ampTABLE1=OB_OTChttpwwwhpmcompdfblogPLAN20B20-20FDA20Exclusivity20amp20Carve-Out20Determinationpdf
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Definitions
bull Behind the Counter
bull Purchaser must be 17 years and older with valid ID
bull Can be male or female
bull Purchased from the pharmacy (not available on the shelves)
bull Over the Counter
bull Anyone of any age can purchase
bull No ID required for purchase
bull Available in the ldquoFamily Planningrdquo aisle instead of behind the pharmacy counter
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Prescription status
bull The 2-pill regimens (LNG 075mg tabs) are prescription only
bull Mostly manufacturer discontinued at this point
bull Patients can talk to the pharmacist about running the OTC EC as a prescription to get coverage through insurance (ie IHFS)
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Which products are truly OTC
Product name (levonorgestrel 15mg) Label Price
Plan B One Step Available OTC unrestricted ~$50
Take Action Available OTC unrestricted ~$40
MyWay Available OTC for 17 and older ~$30
Next Choice One Dose Available OTC for 17 and older ~$40
Fallback Solo Available OTC for 17 and older ~$50
Opcicon One-Step Available OTC for 17 and older ~$30
AfterPill wwwafterpillcom $20 + $5 shipping
Drug Facts and Comparisons July 2015wwwdrugstorecomwwwdrugscomMcKesson Connect connectmckessoncom
Labeled as such ID not required to purchase
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Why is this important
ACCESS
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Access issues
bull Study done in 2013 illustrated the barriers and false information given by pharmacists to females seeking EC
bull 943 pharmacies were called 57 gave correct information about EC access
bull Survey done in 2014 demonstrated that young men have a 1 in 5 chance of not being able to obtain EC
bull 158 pharmacies 22 required a female at the time of purchase
bull Study done in 2005 looked at EC use in adolescents when it was readily available
bull No difference in use of routine contraception no increase in risky sexual behavior
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Why are there barriers to access
bull Ethics
bull Education
bull Safety
bull Cost
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
ellareg
bull Requires prescription for all ages
bull Can get through some websites (dont have to see a physician)
bull ~$60
70httpspharmaafaxyscomafaxysafcor_web_hcp_ellahtmlhttpwwwella-kwikmedcom
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
ellareg availability
bull Distributed by Afaxys
bull Previous distributor dropped ellareg in early 2014
bull OTC status for Ellareg
bull Recommended for OTC availability by European Medicines Agency in 2014
bull Widely available to order through McKesson Cardinal Smith ANDA
Wood S ASEC Webinar May 2014 RHTP FAQ Handout 2013 httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 6214Afaxys Full Line Product Catalog
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Paragardreg
bull Requires prescription for all ages
bullMust be inserted by a specially trained provider
bull ~$800
72httpwwwparagardcomWhat-it-costsaspx
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
EC availability summary
bull PlanB One-Step and Take Action available OTC for all ages
bull Some one dose branded generics still BTCRx
bull No ID verification required
bull Two dose generics are BTCRx
bull Manufacturer discontinue
bull ellareg and Paragardreg available only by prescription
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Question 4
Plan B One Step reg can be purchased by a 15 year old male without proof of age as an over-the-counter item
a True
b False
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Questions
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Referencesbull Allen J Wilcox David B Dunson Clarice R Weinberg James Trussell Donna Day Baird Likelihood of conception with a single act of intercourse providing
benchmark rates for assessment of post-coital contraceptives Contraception Volume 63 Issue 4 2001 211 ndash 215
bull Bell DL Camacho EJ Velasquez AB Male access to emergency contraception in pharmacies a mystery Contraception 2014 90413-415
bull Brache V Cochon L Jesam C et al Immediate pre-ovulatory administration of 30 mg ulipristal acetate significantly delays follicular rupture Hum Reprod 2010252256ndash63
bull Creinin MD Schlaff W Archer DF et al Progesterone receptor modulator for emergency contraception a randomized controlled trial Obstet Gynecol 2006 Nov108(5)1089-97
bull Croxatto HB Brache V Pavez M et al Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 075-mg dose given on the days preceding ovulation Contraception 2004 Dec70(6)442-50
bull Dada OA Godfrey EM Piaggio G et al A randomized double-blind noninferiority study to compare two regimens of levonorgestrel for emergency contraception in Nigeria Contraception 2010 Oct82(4)373-8
bull Daniels K Jones J and Abma J Use of emergency contraception among women aged 15ndash44 United States 2006ndash2010 NCHS Data Brief 2013 No 112 lthttpwwwcdcgovnchsdatadatabriefsdb112pdfgt accessed Jun 2 2013
bull FDA approves Plan B One-Step emergency contraceptive for use without a prescription for all women of child-bearing potential June 20 2013 httpwwwfdagovNewsEventsNewsroomPressAnnouncementsucm358082htm Accessed 652014
bull Finer LB Zolna MR Unintended pregnancy in the United States Incidence and disparities 2006 Contraception Nov 2011 84(5) 478ndash485
bull Gazdag M Kardos L Frey B Kapp N Philip M (2014 June 4) Womenrsquos BMI as a factor in EC failure An open discussion on the data available to date [Webinar] Hosted by the International and Eurpoean consortium for Emergency Contraception
bull Gemzell-Danielsson K Berger C Lalitkumar PGL Emergency contraception mdash mechanisms of action Contraception 201387300ndash308
bull Glasier A Cameron ST Fine PM et al Ulipristal acetate versus levonorgestrel for emergency contraception a randomised non-inferiority trial and meta-analysis Lancet 2010 375 555ndash62
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Referencesbull Glasier A Cameron ST Blithe D et al Can we identify women at risk of pregnancy despite using emergency contraception Data from randomized trials of ulipristal
acetate and levonorgestrel Contraception 2011 Oct84(4)363-7
bull Gould JE Overstreet JW Hanson FW Assessment of human sperm function after recovery from the female reproductive tract Biol Reprod 198431888ndash94
bull Guttmacher Institute State Policies In Brief Available at httpswwwguttmacherorgstatecenterspibsspib_ECpdf Accessed June 4 2014
bull Kapp N Abitbol JL Matheacute H et al Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception Contraception 2015 Feb91(2)97-104
bull Lalitkumar PGL Lalitkumar S Meng CX et al Mifepristone but not levonorgestrel inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model Hum Reprod 2007223031ndash7
bull NorLevo 15 mg tablet [Package Leaflet Information for the user] Paris France HRA Pharma 2013 httpwwwimbieimagesuploadedswedocuments2126041PA1166_002_001a60606c0-00f0-4866-bc34-91bdfd679b1e000001PACKAGE20LEAFLET2015131128pdf Accessed 121813
bull Novikova N Weisberg E Stanczyk FZ Croxatto HB Fraser IS Effectiveness of levonorgestrel emergency contraception given before or after ovulationndasha pilot study Contraception 200775112ndash8
bull Ortiz ME Croxatto HB Bardin CW Mechanisms of action of intrauterine devices Obstet Gynecol Surv 199651S42ndash51
bull Plan B One-Step [Highlights of prescribing information] Pomona New York Gedeon Richter Ltd 2009 httpwwwplanbonestepcompdfPlanBOneStepFullProductInformationpdf Accessed 652014
bull Planned Parenthood ldquoWhatrsquos the Best Emergency Contraception for Yourdquo 2013 httpwwwplannedparenthoodorghealth-center Accessed 622014
bull Reproductive Health Technologies Project ldquoWhere should EC Berdquo Aug 2013 wwwrhtporgcontraceptionemergencydocumentsWhereShouldECBeAugust12013pdf Accessed 652014
bull Reproductive Health Technologies Project ldquoWomenrsquos Health Advocates Celebrate FDA Decision to Remove Restrictions on Generic Emergency Contraception Generic Emergency Contraceptive Pills Move One Step Closer to Full Over-the-Counter Status Feb 2013 httpwwwrhtporgdocumentsRHTPPressRelease-FDADecisiontoRemoveRestrictionsonGenericECpdf Accessed 652014
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
Referencesbull Reproductive Health Technologies Project ldquoFrequently Asked Questions The Impact of Weight on Efficacy of Emergency Contraceptionrdquo Dec 2013
httpwwwrhtporgcontraceptionemergencydocumentsFAQECEfficacyandBodyWeightDecember2013pdf Accessed 622014
bull Roblero L Guadarrama A Lopez T Zegers-Hochschild F Effect of copper ion on the motility viability acrosome reaction and fertilizing capacity of human spermatozoa in vitro Reprod Fertil Dev 19968871ndash4
bull Shea K (2014 May14) EC in a Health Center Setting the EC4U Project [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Trussell J Rodriacuteguez G Ellertson C New estimates of the effectiveness of the Yuzpe regimen of emergency contraception Contraception 199857363ndash9
bull Trussell J Raymond EG Emergency Contraception A Last Chance to Prevent Unintended Pregnancy November 2011 Available at httpecprincetoneduquestionsec-reviewpdf
bull von Hertzen et al Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception Task Force on Postovulatory Methods of Fertility Regulation Lancet 1998 Aug 8352(9126)428-33
bull von Hertzen H Piaggio G Ding J Low dose mifepristone and two regimens of levonorgestrel for emergency contraception a WHO multicentre randomised trial Lancet 2002 Dec 7360(9348)1803-10
bull Wilcox AJ Weinberg CR Baird DD Timing of sexual intercourse in relation to ovulation Effects on the probability of conception survival of the pregnancy and sex of the baby NEJM 19953331517ndash21
bull Wilcox AJ Dunson D Baird DD The rdquofertile windowrdquo in the menstrual cycle day specific estimates from a prospective study BMJ 200018(321)1259ndash62
bull Wilcox AJ Dunson DB Weinberg CR Trussell J Baird DD Likelihood of conception with a single act of intercourse providing benchmark rates for assessment of post-coital contraceptives Contraception 200163 (4)211 ndash 215
bull Wilkinson TA Vargas G Fahey N et al laquoIrsquoll see what I can doraquo What adolescents Experience When Requesting Emergency Contraception J Adolesc Health 20145414-19
bull Wood S (2014 May 14) The Regulatory Context [Webinar] In ASEC ldquoEC Efficacy and Weight Answers Questions and Finding a Way Forwardrdquo Retrieved from httpsarhpadobeconnectcom_a707384277p8gw6h4407g
bull Yuzpe AA Lance WJ Ethinylestradiol and DL-norgestrel as a potential contraceptive Fertil Steril 197728932ndash6
