Best Practices: Eight Principles for Safer Opioid Prescribing · Planning Committee, Disclosures...

Best Practices: Eight Principles for Safer Opioid Prescribing

Lynn R. Webster, MD

Vice President of Scientific Affairs

PRA International

Salt Lake City, UT

February 11, 2015

Dr Webster: Disclosures

• 12-Month disclosures of financial relationships with commercial interests:

• This presentation does not contain off-label or investigational use of drugs or products

Honorarium: Consultant Honorarium: Advisory Board Travel Expenses

Acura Pharmaceuticals Depomed Acura Pharmaceuticals

AstraZeneca Egalet AstraZeneca

BioDelivery Sciences International Inspirion Pharmaceuticals BioDelivery Sciences International

CVS Caremark Insys Therapeutics Bristol-Myers Squib (BMS)

Grunenthal USA Kaleo Depomed

Mallinckrodt Pharmaceuticals Mallinckrodt Pharmaceuticals Grunenthal USA

Nevro Corporation Signature Therapeutics Inspirion Pharmaceuticals

Synchrony Healthcare Teva Pharmaceuticals Insys Therapeutics

Travena Jazz Pharmaceuticals

Kaleo

Mallinckrodt Pharmaceuticals

Nektar Therapeutics

Nevro Corporation

Orexo Pharmaceuticals

Teva Pharmaceuticals

Travena

Planning Committee, Disclosures

• Vitaly Gordin, MD Director of Pain Division Penn State Hershey Medical Center Hershey, PA

No relevant financial relationships

• Jennifer Westlund, MSW Director of Education American Academy of Pain Medicine


• Angela Casey VP, Medical Director PharmaCom Group


Target Audience

• The overarching goal of PCSS-O is to offer evidence-based

trainings on the safe & effective prescribing of opioid

medications in the treatment of pain &/or opioid addiction

• Our focus is to reach providers &/or providers-in-training

from diverse healthcare professions including physicians,

nurses, dentists, physician assistants, pharmacists, &

program administrators

Educational Objectives

• At the conclusion of this activity participants should be able to:

1. Understand the major risk factors for unintentional opioid

overdose deaths in patients with chronic pain

2. Devise a plan to implement 8 simple principles for safer

opioid prescribing that can save lives

Major Reasons for Opioid-Associated Deaths

• Over-prescribing (Physician)

Starting dose too high

Dose escalation too rapid

Over reliance on conversion tables

Inadequate risk assessment

• Non-adherence (Patient)

To control pain

To “cope”

Substance abuse

• Unanticipated co-morbidities

QT prolongation

Pharmacogenetics & methadone metabolism

Sleep disordered breathing

Rates of Prescription Opioid Sales & Deaths, 1999-2013

0

1

2

3

4

5

6

7

8

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Rate

Sales per kg per 100,000 people Deaths per 100,000 people

Centers for Disease Control and Prevention. CDC Vital Signs: Prescription Painkiller Overdoses in the US. 2011. Chen LH, et al. Drug-poisoning deaths involving opioid analgesics: United States, 1999-2011. NCHS data brief, no. 166. Hyattsville, MD: NCHS. 2014. Warner M, et al. Trends in drug-poisoning deaths involving opioid analgesics and heroin: United States, 1999-2012. CDC Health E-Stats. 2014. Chen LH, et al. Quick Stats. MMWR. 2015;64:32..

Number of Deaths Involving Opioid Analgesics, 1999-2013

4030

16235

0

2000

4000

6000

8000

10000

12000

14000

16000

18000

1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Nu

mb

er

of

death

s

Warner M, et al. Trends in drug-poisoning deaths involving opioid analgesics and heroin: United States, 1999-2012. CDC Health E-Stats. 2014. Chen LH, et al. Quick Stats. MMWR. 2015;64:32.

4-fold increase in deaths since 1999

Prescription Opioid Deaths Are a Growing Problem Among Women

6

3.7

0

1

2

3

4

5

6

7

Male Female

Rate

pe

r 1

00,0

00

0

1000

2000

3000

4000

5000

6000

7000

Nu

mb

er

of

death

s a

mo

ng

w

om

en

CDC Vital Signs. Prescription Painkiller Overdoses. A growing epidemic, especially among women. 2013. Paulozzi L. CDC. Populations at risk for opioid overdose. 2012. www.fda.gov/downloads/Drugs/NewsEvents/UCM300859.pdf

Prescription opioid overdose deaths among women have increased >400% since 1999, compared to 265% among men

Although men are still more likely to die of prescription opioid overdoses, the gap between men & women is closing

http://www.fda.gov/downloads/Drugs/NewsEvents/UCM300859.pdf

1. Assess patients for risk of abuse before starting opioid therapy and manage accordingly

2. Watch for and treat comorbid mental disease if present

3. Conventional conversion tables can cause harm and should be used cautiously when rotating (switching) from one opioid to another

4. Avoid combining benzodiazepines with opioids, especially during sleep hours

5. Start methadone at a very low dose and titrate slowly regardless of whether your patient is opioid tolerant or not

6. Assess for sleep apnea in patients on high daily doses of methadone or other opioids and in patients with a predisposition

7. Tell patients on long-term opioid therapy to reduce opioid dose during upper respiratory infections or asthmatic episodes

8. Avoid using long-acting opioid formulations for acute, post-operative, or trauma-related pain

Webster LR. Pain Med. 2013;14:959-61.

Assess patients for risk of abuse before starting opioid

therapy & manage accordingly

BEST PRACTICES

1


Oreos As Addictive As Cocaine? For Rats, At Least

Photo by Bob MacDonnell courtesy of Connecticut College

Student-faculty research suggests Oreos can be compared to drugs of abuse in lab rats. Connecticut College News. October 15, 2013. www.conncoll.edu/news/news-archive/2013/student-faculty-research-suggests-oreos-can-be-compared-to-drugs-of-abuse-in-lab-rats.htm

http://www.conncoll.edu/news/news-archive/2013/student-faculty-research-suggests-oreos-can-be-compared-to-drugs-of-abuse-in-lab-rats.htm































Vulnerability to Opioid Addiction

Individuals respond differently to opioid exposure

No addictive disease with exposure

Addictive disease after opioid exposure

No addictive disease due to lack of exposure

Genetic Vulnerability to Addiction?

Fischer

344 Abstinence

Drug

rejecting

Lewis Poly-

substance

Abuse

Drug

seeking

Sprague-

Dawley Average

Drug

neutral

Webster LR, Dove B. Avoiding Opioid Abuse While Managing Pain: A Guide for Practitioners. North Branch, MD: Sunrise River Press. 2007.

Level of Abuse in Stressful Environments

Low Moderate High

Patient stress level

Dru

g-a

bu

sin

g b

eh

avio

r


Screening Tools to Assess Patient Risk Before Prescribing Opioids

• Use one of several available tools to assess patient risk of developing problematic drug-taking behaviors

Based on biological, social, & psychiatric risk factors

• Implement a plan according to risk level

eg, for high-risk patients, refer for psychiatric evaluation or

co-manage with a chemical dependency expert prior to

opioid trial

Tool # of items Administered by

ORT Opioid Risk Tool 5 patient

SOAPP® Screener & Opioid Assessment for Patients

with Pain

24, 14, or

5 patient

DIRE Diagnosis, Intractability, Risk, & Efficacy Score 7 clinician

Webster LR. Pain Med. 2013;14:959-61. Webster LR, Webster RM. Pain Med. 2005:6:432-42. Butler SF, et al. Pain. 2004;112:65-75. Belgrade MJ, et al. J Pain. 2006;7:671-81.

Identify Misuse Once Opioid Treatment Begins

• Periodic monitoring for effects on analgesia, daily activities, adverse events, ADRBs, cognition, function, & QOL can be assisted by tools

• Check state prescription monitoring programs

• Utilize measures such as urine drug testing

Tool # of items Administered by

PADT Pain Assessment & Documentation Tool 41 clinician

COMM Current Opioid Misuse Measure 17 patient

Webster LR. Pain Med. 2013;14:959-61. Passik SD, et al. J Opioid Manage. 2005:257-66. Passik SD, et al. Clin Ther. 2004;552-61. Butler SF, et al. Pain. 2007;130:144-56.

ADRBs=aberrant drug-related behaviors; QOL=quality of life

Watch for & treat comorbid mental disease if present

BEST PRACTICES

2 2


Overlapping Effects

Pain

disorders

Psychiatric disorders

50%

overlap

Peles E, et al. Pain. 2005;113:340-6. Potter JS, et al. Am J Drug Alcohol Abuse. 2008;34: 101-7. Rosenblum A, et al. JAMA. 2003;289:2370-8. Sheu R, et al. Pain Med. 2008;9:911-7.

Overlapping Effects

60%

overlap

Addiction disorders

Psychiatric disorders

National Institute on Drug Abuse. Comorbid Drug Abuse and Mental Illness. A Research Update from the National Institute on Drug Abuse. 2007. National Institute on Drug Abuse. Comorbidity: Addiction and Other Mental Illness. Research Report Series. NIH Publication No. 10-5771. 2010.

Comorbid Pain & Mental Disease

• Co-occurrence of mental health disorders with chronic pain place patient at high risk for:

Misuse

Drug-drug interactions

Overdose

• Assess for the presence of mental disease before initiating opioid therapy

When indicated, consult with experts in mental health fields

to co-ordinate care


An Olympian Challenge: Managing a Critical Interplay

Addiction disorder

Psychiatric disorder

Pain disorder

A “trio diagnosis”


Suicide

161.6 151.6

182.8

197.1 199.5 198.4

212.7

228.4

16.9 17.8 24.5

29.9 26.8 29.6 32.9 31.7

0

25

50

75

100

125

150

175

200

225

250

2004 2005 2006 2007 2008 2009 2010 2011

Nu

mb

er

of

ED

vis

its f

or

dru

g-

rela

ted

su

icid

e a

ttem

pts

(t

ho

usan

ds)

All drugs Opioid analgesics

87% increase in opioid suicide attempts

41% increase in drug suicide attempts

Substance Abuse and Mental Health Services Administration. Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. HHS Publication No. (SMA) 13-4760, DAWN Series D-39. Rockville, MD: SAMHSA, 2013.

Why Suicide? Non-Pain Patients

Escape from severe suffering Only option

Permanent solution Hopelessness

Kraft TL, et al. Arch Suicide Res. 2010;14:375-82.

Conventional conversion tables can cause harm & should be used

cautiously when rotating (switching) from one opioid to another

BEST PRACTICES

3 3


WARNING! Equianalgesic ≠ Conversion Tables

• Equianalgesic tables provide insufficient guidance to determine the equivalent doses of different opioids

Individual consideration is necessary for every patient

Webster LR. Pain Med. 2013;14:959-61. Knotkova H, et al. J Pain Symptom Manage. 2009; 38:426-39. Webster LR, Fine PG. Pain Med. 2012;13:562-70. Webster LR, Fine PG. Pain Med. 2012;13:571-4.

Steps in Opioid Rotation

Webster LR. Pain Med. 2013;14:959-61. Webster LR, Fine PG. Pain Med. 2012;13:571-4.

• Slowly decrease one opioid while

slowly titrating the new opioid to effect


10%-20% increments IR Supplement

10%-30% increments




• In most cases, the complete switch

can occur within 3-4 weeks

• If you are not experienced in switching

opioids in patients on long-term opioid

therapy, seek expert consultation

Avoid combining benzodiazepines with opioids, especially during sleep hours

BEST PRACTICES

4


Most Common Drugs Involved in Overdoses in the United States

• In 2013, there were 43,982 drug overdose deaths

22,767 (51.8%) were related to pharmaceuticals

− 16,235 (71.3%) involved opioid analgesics

− 6,973 (30.6%) involved benzodiazepines

• People who died of drug overdoses often had a combination of benzodiazepines & opioids in their bodies

• In 2011, ~1.4 million ED visits involved nonmedical use of pharmaceuticals

501,207 visits involved anti-anxiety & insomnia medications

420,040 visits involved opioid analgesics

CDC. Prescription Drug Overdose in the United States: Fact Sheet. 2015. www.cdc.gov/homeandrecreationalsafety/overdose/facts.html

http://www.cdc.gov/homeandrecreationalsafety/overdose/facts.html

Benzodiazepines & Chronic Pain Patients

• Enhance the respiratory depressant effects of opioids

Frequently co-prescribed with opioids (up to 50% of patients)

− In 1 population, 80% of patients prescribed high-dose opioids were co-prescribed benzodiazepines

− More common in chronic pain patients with substance use disorders

• Consider an alternative

For anxiety disorders

When a sleep aid is indicated, eg, an anticonvulsant or low-dose trazodone

− For patients with neuropathic pain, low-dose trazodone at bedtime may be dually beneficial

Webster LR. Pain Med. 2013;14:959-61. Webster LR, et al. Postgraduate Med. 2015; early online. Deyo RA, et al. J Am Board Fam Med. 2011;24:717-27. King SA, Strain JJ. Clin J Pain. 1990;6:143-7. Manchikanti L, et al. Pain Physician. 2009;12:259-67. Braden JB, et al. Arch Intern Med. 2010;170:1425-32. Dasgupta N. Opioid analgesic prescribing and overdose mortality in North Carolina [dissertation]. Chapel Hill, NC: University of North Carolina at Chapel Hill; 2013. Weisner CM, et al. Pain. 2009;145:287-93.

Start methadone at a very low dose & titrate slowly regardless of whether your patient is opioid tolerant or not

BEST PRACTICES

5


CDC. Prescription Drug Overdoses. CDC Vital Signs; July 2012.

Methadone-Related Deaths

• Methadone contributed to nearly 1 in 3 prescription opioid deaths in 2009

• 5,000 people die every year of overdose related to methadone

• 6 times as many people died of methadone overdose in 2009 than a decade before

Death Rate from Overdose Caused by a Single Prescription Painkiller

0

2

4

6

8

10

12

Death

rate

pe

r 1

00 k

ilo

gra

ms

Substance Abuse and Mental Health Administration, Center for Behavioral Statistics and Quality, Drug Abuse Warning Network Medical Examiner Component, 2009. CDC. Prescription Drug Overdoses. CDC Vital Signs; July 2012.

2 4 6 8 10 12 14 16 18 20 22 24

Blo

od

le

ve

l

Days

Analgesia

Toxicity

α (analgesic) β (non-analgesic)

Hours

2 3 4 5 6 7

Simulated Methadone Dosing

Webster LR. Unintentional overdose deaths: reversing the trend. Presented at: The American Academy of Pain Medicine’s 28th Annual Meeting; February 22-26, 2012; Palm Springs, CA.

Legal Review of Opioid Deaths: Methadone

• Starting doses 20-140 mg/day

Most <30 mg/day

• ~90% opioid tolerant

• ~80% died within 4 days of first methadone

• Snoring common

• Occasional upper respiratory infection/flu onset preceded death

Webster LR, Rich B. Pain Med. 2011;12:S59-65.

Initiating Methadone

• Consider starting patients, whether or not they are opioid naïve, on ≤15 mg/day in divided doses (qh8)

• Increase the total daily dose by no more than 25%-50%, no more frequently than weekly


If you are not experienced

prescribing methadone, consult with

a clinician who is

Assess for sleep apnea in patients on high daily doses of methadone or other opioids & in patients with a

predisposition

BEST PRACTICES

6


Sleep Disorders & Opioids: Events per Hour

0

10

20

30

40

50

60

70

80

90

Perc

en

t o

f p

ati

en

ts

AHI ≥5 events/hour CAI ≥5 events/hour

OMAI ≥5 events/hour

Sleep apnea: type indeterminate

Bars indicate hi/lo of 95% CI

Webster LR, et al. Pain Med. 2008;9:425-32.

n = 140

AHI=apnea-hypopnea index

CAI=central apnea index

OMAI=obstructive & mixed apnea Index

Rate Ratios by Increase of Morphine Equivalent Dose

0.8

0.9

1

1.1

1.2

1.3

1.4

1.5

1.6

1.7

1.8

0 25 50 75 100 125 150 175 200

Rate

rati

o

Morphine equivalent dose (mg/day)

Central p<.001

Hypopnea p<.001

Obstructive p<.001

REM apnea/hypopneap=.86

Walker JM, et al. J Clin Sleep Med. 2007;3:455-61.

AWAITING PERMISSION

TO USE FROM

PUBLISHER

Assess for Sleep Apnea

• Refer the following patients for formal sleep apnea evaluation

Patients who require >50 mg/day of methadone

Patients who require >150 mg/day of morphine equivalent

dose of other opioids

Patients with a predisposition or risk factors for sleep apnea

• At risk patients may require inpatient evaluation to monitor for & determine safety of opioid therapy


Tell patients on long-term opioid therapy to reduce opioid dose during

upper respiratory infections or asthmatic episodes

BEST PRACTICES

7


Reduce Opioid Dose During

• Because of a decreased margin of safety, advise patients to reduced their daily opioid doses by ≥30% during events with acute respiratory tract compromise

These include:

− Flu

− Pneumonia

− Upper respiratory infections

− Cigarette use

− Chronic obstructive pulmonary disease

− Asthmatic episodes

Webster LR. Pain Med. 2013;14:959-61. Webster LR, et al. Postgrad Med. 2015; online first.

Avoid using long-acting opioid formulations for acute, post-operative,

or trauma-related pain

BEST PRACTICES

8


Reserve Long-Acting Opioids for Opioid-Tolerant Patients

• Reserve long-acting/extended-release opioids, including transdermal patches, for patients who have developed tolerance to opioids

ie, who already take regular, daily, around-the-clock opioids

• Do not use for acute, postoperative, or trauma-related pain

Webster LR. Pain Med. 2013;14:959-61. Webster LR, et al. Postgrad Med. 2015; online first.

References

• Belgrade MJ, et al. J Pain. 2006;7:671-81.

• Braden JB, et al. Arch Intern Med. 2010;170:1425-32.

• Butler SF, et al. Pain. 2004;112:65-75.

• Butler SF, et al. Pain. 2007;130:144-56.

• CDC Vital Signs. Prescription Painkiller Overdoses in the US. 2011.

• CDC Vital Signs. Prescription Drug Overdoses. July 2012.

• CDC Vital Signs. Prescription Painkiller Overdoses. A growing epidemic, especially among women. 2013.

• CDC. Prescription Drug Overdose in the United States: Fact Sheet. 2015.

• Chen LH, et al. Drug-poisoning deaths involving opioid analgesics: United States, 1999-2011. NCHS data brief, no. 166. Hyattsville, MD: NCHS. 2014.

• Chen LH, et al. Quick Stats. MMWR. 2015;64:32.

• Dasgupta N. Opioid analgesic prescribing and overdose mortality in North Carolina [dissertation]. Chapel Hill, NC: University of North Carolina at Chapel Hill; 2013.

• Deyo RA, et al. J Am Board Fam Med. 2011;24:717-27.

• King SA, Strain JJ. Clin J Pain. 1990;6:143-7.

• Knotkova H, et al. J Pain Symptom Manage. 2009; 38:426-39.

• Kraft TL, et al. Arch Suicide Res. 2010;14:375-82.

• Manchikanti L, et al. Pain Physician. 2009;12:259-67.

• NIDA. Comorbid Drug Abuse and Mental Illness. A Research Update from the National Institute on Drug Abuse. 2007.

• NIDA. Comorbidity: Addiction and Other Mental Illness. Research Report Series. NIH Publication No. 10-5771. 2010.

• Passik SD, et al. Clin Ther. 2004;552-61.

• Passik SD, et al. J Opioid Manage. 2005:257-66.

• Paulozzi L. CDC. Populations at risk for opioid overdose. 2012.

• Peles E, et al. Pain. 2005;113:340-6.

• Potter JS, et al. Am J Drug Alcohol Abuse. 2008;34: 101-7.

• Rosenblum A, et al. JAMA. 2003;289:2370-8.

• Sheu R, et al. Pain Med. 2008;9:911-7.

• Student-faculty research suggests Oreos can be compared to drugs of abuse in lab rats. Connecticut College News. October 15, 2013.

• SAMHSA, Center for Behavioral Statistics and Quality, Drug Abuse Warning Network Medical Examiner Component, 2009.

• SAMHSA. Drug Abuse Warning Network, 2011: National Estimates of Drug-Related Emergency Department Visits. HHS Publication No. (SMA) 13-4760, DAWN Series D-39. Rockville, MD: SAMHSA, 2013.

• Walker JM, et al. J Clin Sleep Med. 2007;3:455-61.

• Warner M, et al. Trends in drug-poisoning deaths involving opioid analgesics and heroin: United States, 1999-2012. CDC Health E-Stats. 2014.

• Webster LR, Webster RM. Pain Med. 2005:6:432-42.

• Webster LR, Dove B. Avoiding Opioid Abuse While Managing Pain: A Guide for Practitioners. North Branch, MD: Sunrise River Press. 2007.

• Webster LR, et al. Pain Med. 2008;9:425-32.

• Webster LR, Rich B. Pain Med. 2011;12:S59-65

• Webster LR, Fine PG. Pain Med. 2012;13:562-70.

• Webster LR, Fine PG. Pain Med. 2012;13:571-4.

• Webster LR. Unintentional overdose deaths: reversing the trend. Presented at: The American Academy of Pain Medicine 28th Annual Meeting; Feb 22-26, 2012; Palm Springs, CA.

• Webster LR. Pain Med. 2013;14:959-61.

• Webster LR, et al. Postgraduate Med. 2015; early online.

• Weisner CM, et al. Pain. 2009;145:287-93.

Questions & Answers

Please type your question in the

text chat box

PCSS-O Colleague Support Program

• PCSS-O Colleague Support Program is designed to offer general

information to health professionals seeking guidance in their clinical

practice in prescribing opioid medications.

• PCSS-O Mentors comprise a national network of trained providers with

expertise in addiction medicine/psychiatry and pain management.

• Our mentoring approach allows every mentor/mentee relationship to be

unique and catered to the specific needs of both parties.

• The mentoring program is available at no cost to providers.

• Listserv: A resource that provides an “Expert of the Month” who will

answer questions about educational content that has been presented

through PCSS-O project. To join email: [email protected].

For more information on requesting or becoming a mentor visit:

pcss-o.org/ask-colleague

mailto:[email protected]



http://pcss-o.org/ask-colleague





PCSS-O is a collaborative effort led by American Academy of Addiction Psychiatry (AAAP) in

partnership with: Addiction Technology Transfer Center (ATTC), American Academy of

Neurology (AAN), American Academy of Pain Medicine (AAPM), American Academy of

Pediatrics (AAP), American College of Physicians (ACP), American Dental Association (ADA),

American Medical Association (AMA), American Osteopathic Academy of Addiction Medicine

(AOAAM), American Psychiatric Association (APA), American Society for Pain Management

Nursing (ASPMN), International Nurses Society on Addictions (IntNSA), and Southeast

Consortium for Substance Abuse Training (SECSAT).

For more information visit: www.pcss-o.org

For questions email: [email protected]

Twitter: @PCSSProjects

Funding for this initiative was made possible (in part) by Providers’ Clinical Support System for Opioid Therapies (grant no. 1H79TI025595) from SAMHSA. The views expressed in written

conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names,

commercial practices, or organizations imply endorsement by the U.S. Government.

http://www.pcss-o.org/






https://twitter.com/PCSSprojects

http://www.twitter.com/PCSSProjects

Best Practices: Eight Principles for Safer Opioid Prescribing · Planning Committee, Disclosures...

Documents

Transcript of Best Practices: Eight Principles for Safer Opioid Prescribing · Planning Committee, Disclosures...