Approved Prescription Products for Menopausal Symptoms in ...

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Approved Prescription Products for Menopausal Symptoms in the United States and Canada

Oral estrogen products Revised: May 21, 2015

(Providers should check the full prescribing information for appropriate dosages for the indication and any updates or information that is not provided here, such as warnings and contraindications.)

Active Ingredient(s) Product Name(s) Dosages (mg/d)

17β-estradiol* Estrace‡ Various generics

0.5, 1.0, 2.0 (administer cyclically)

Conjugated estrogens Premarin 0.3, 0.45†, 0.625, 0.9†, 1.25

Synthetic conjugated estrogens, B

Enjuvia† 0.3, 0.45, 0.625, 0.9, 1.25

Conjugated estrogens, CSD (synthetic)

PrC.E.S.‡ Prpms-Conjugated estrogens, CSD‡

0.3, 0.625, 0.9, 1.25

Esterified estrogens Menest†

Estragyn‡

0.3, 0.625, 1.25, 2.5 (administer cyclically)

0.3, 0.625 (administer cyclically)

Estropipate Various generics† 0.625 (0.75 estropipate), 1.25 (1.5), 2.5 (3.0), 5.0 (6.0)

*Bioidentical: defined as compounds that have the same chemical and molecular structure as hormones that are produced in the body †Available in the United States but not Canada

‡Available in Canada but not the United States

Product names not marked are available in both the United States and Canada.

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Transdermal estrogen products Revised: May 21, 2015


Active Ingredient(s) Product Name Dosage (mg E2/day)

Patch

17β-estradiol* Alora†

Climara

Estraderm†

Estradot‡

Minivelle†

Oesclim‡

Vivelle-Dot†

Various generics

0.025, 0.05, 0.075, 0.1 twice/wk

0.025, 0.0375,† 0.05, 0.06,† 0.075, 0.1 once/wk

0.05, 0.1 twice/wk

0.025, 0.0375, 0.05, 0.075, 0.1 twice/wk

0.025, 0.0375, 0.05, 0.075, 0.1 twice/wk

0.025, 0.0375, 0.05, 0.075, 0.1 twice/wk

0.025, 0.0375, 0.05, 0.075, 0.1 twice/wk

Transdermal gel

17β-estradiol* Divigel

EstroGel

Elestrin†

0.25, 0.5, 1.0

0.75,† 1.5 (usually cyclic, adjust to control symptoms) ‡

0.52 (adjust based on individual response)

Transdermal spray

17β-estradiol* Evamist† 1.53 (1 spray/d initially, adjust dosage by response)


‡Available in Canada but not the United States

Product names not marked are available in both the United States and Canada.

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Vaginal estrogen products Revised: May 21, 2015


Active Ingredient(s)

Product Name Indication

Dosage

Creams

17β-estradiol* Estrace Vaginal Cream†

Vulvar and vaginal atrophy

Initial: 2-4 g/d for 1-2 wk Maintenance: 1 g 1-3 times/wk (0.1 mg estradiol/g)

Conjugated estrogens

Premarin Vaginal Cream Atrophic vaginitis Kraurosis vulvae US: Moderate to severe dyspareunia Canada: Dyspareunia

US labeling For atrophic vaginitis and kraurosis vulvae: 0.5-2 g/d (0.625 mg conjugated estrogens/g) for 21 d then off 7 d For moderate to severe dyspareunia: 0.5 g twice weekly or 0.5 g/d for 21 d then off 7 d, or twice/wk

‡

Canadian Labeling Low dose: 0.5 g intravaginal or topical twice/wk Maximum recommended dose: 0.5 g/d intravaginally or topically for 21 d then off 7d. Start with 0.5 g/d. Dosage adjustments (0.5 to 2 g) may be made based on individual response

Estrone* Estragyn Vaginal Cream§ Senile vaginitis Prurit vulvae Kraurosis vulvae

2-4 g/d (1 mg active ingredient/g) adjusted to the lowest amount that controls symptoms. Administration should be cyclic (eg, for 21 d then off 7 d)

Rings

17β-estradiol*

Estring

US: Moderate to severe symptoms of vulvar and vaginal atrophy due to menopause

Canada: Atrophic vaginitis Dyspareunia Dysuria and urinary urgency

2 mg (releases 7.5 µg/d) for 90 days

Continued on page 4

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Continued from page 3

Estradiol acetate* Femring†

Moderate to severe vasomotor symptoms due to menopause Moderate to severe vulvar and vaginal atrophy due to menopause

0.05 mg/d, 0.10 mg/d for 90 days (both strengths release systemic levels and require consideration of a progestogen if the uterus is intact)

Tablet

Estradiol* Vagifem Atrophic vaginitis due to menopause

10 µg, 25 µg Initial: 1 tablet/d for 2 wk Maintenance: 1 tablet twice/wk


‡NAMS suggests twice/wk dosing as suggested in the Canadian low-dose option

§Available in Canada but not the United States

Products without asterisks are available in the United States and Canada.

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Combination estrogen-progestogen products Revised: May 21, 2015


Active Ingredient(s) Product Name Dosage

Oral continuous-cyclic

Conjugated estrogens (E) + medroxyprogesterone acetate (P)

Premphase*

Premplus Cycle†

0.625 mg E + 5.0 mg P (2 tablets: E days 1-14, E + P days 15-28)

0.625 mg E + 10.0 mg P (2 tablets: E days 1-14, E + P days 15-28)

Oral continuous-combined


Prempro* Premplus†

0.3 or 0.45 mg E + 1.5 mg P*, 0.625 mg E + 2.5 or 5.0 mg P

Ethinyl estradiol (E) + norethindrone acetate (P)

femhrt*, femHRT Lo†

femhrt*, femHRT†

2.5 µg E + 0.5 mg P

5 µg E + 1 mg P

17β -estradiol (E) + norethindrone acetate (P)

Activella*

Activelle LD†

Activelle†

0.5 mg E + 0.1 mg P, 1 mg E + 0.5 mg P

0.5 mg E + 0.1 mg P

1 mg E + 0.5 mg P

17β-estradiol (E) + drospirenone (P)

Angeliq 1 mg E + 0.5 mg P*, 0.5 mg E + 0.25 mg P*, 1 mg E + 1 mg P†

Oral intermittent-combined

17β-estradiol (E) + norgestimate (P)

Prefest* 1 mg E and 1 mg E + 0.09 mg P (E alone for 3 d, followed by E+P for 3 d, repeated continuously)


Premplus Cycle† 0.625 mg E + 10 mg P (2 tablets: E for 28 d, P days 15-28)

Transdermal continuous-combined

17β-estradiol (E) + norethindrone acetate (P)

CombiPatch*

Estalis†

0.05 mg E + 0.14 mg P twice/wk

0.05 mg E + 0.25 mg P twice/wk

17β-estradiol (E) + levonorgestrel (P)

Climara Pro 0.045 mg E + 0.015 mg P once/wk

*Available in the United States but not Canada †Available in Canada but not the United States

Products not marked are available in both the United States and Canada

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Progestogens Revised: May 21, 2015 (Providers should check the full prescribing information for appropriate dosages for the indication and any updates or information that is not provided here, such as warnings and contraindications.)

Active Ingredient(s) Product Name Dosage (mg/d)

Medroxyprogesterone acetate

Provera

Various generics

2.5, 5, 10 (administer cyclically)

Micronized progesterone* Prometrium 100,† 200 (administer cyclically)

* Bioidentical: defined as compounds that have the same chemical and molecular structure as hormones that are produced in the body †Available in the United States but not Canada

Products not marked are available in both the United States and Canada

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Other oral products Revised: May 21, 2015


Active Ingredient(s) Indication

Product Name Indication

Dosage (mg/d)

Conjugated estrogens + bazedoxifene

Moderate to severe vasomotor symptoms

Duavee 0.45 (E) + 20 (bazedoxifene)

Ospemifene

Moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause

Osphena* 60

Paroxetine

Moderate to severe vasomotor symptoms

Brisdelle* 7.5

*Available in the United States but not Canada Products not marked are available in both the United States and Canada.

Copyright © 2015 The North American Menopause Society

WOMEN’S INTERNATIONAL PHARMACY

RESOURCE GUIDE FOR HEALTH PRACTITIONERS Women’s International Pharmacy has compounded thousands of unique formulations since 1985. We are offering the following information to illustrate designing a drug regimen, which can be individualized for each patient. We are able to customize using bioidentical hormones in a large selection of dosage forms when prescribed. This information is a general outline of various dosage forms and possible combinations. These are just a few of the many possible combinations. Common Abbreviations D – DHEA Te – Testosterone E1 – Estrone Pr – Pregnenolone E2 – Estradiol T3 – Liothyronine E3 – Estriol T4 – Levothyroxine H – Hydrocortisone E1E2E3 – Triest or Triple Estrogen P – Progesterone E2E3 – Biest or Biestrogen The formulas given below use these abbreviations. This format is used on the prescription label. CAPSULES Women’s International Pharmacy has compounded many different capsule formulations. We could never list all of them here for you. Olive oil is used to suspend the powder in our capsules unless other oils are requested. Multiple hormones may be combined in a single capsule. We use colored capsules as an identification aid. Colorless and vegetarian capsules may also be chosen. Capsules may be used for oral, sublingual, vaginal, rectal, and topical (open and empty capsule) application. Estrone/Estradiol/Estriol (mg)/Capsule (This combination of estrogens is popularly called “triest” or “triple estrogen.” Ratios may vary, e.g., 10:10:80, 5:5:90.) E1E2 0.03/E3 0.24 E1E2 0.15/E3 1.2 E1E2 0.063/E3 0.5 E1E2 0.25/E3 2 E1E2 0.1/E3 0.8 E1E2 0.5/E3 4 E1E2 0.125/E3 1 Estradiol/Estriol (mg)/Capsule (This combination is popularly called “biest” or “biestrogen.” Ratios may vary, e.g., 20:80, 30:70.) E2 0.25/E3 1 E2 0.5/E3 2 E2 0.125/E3 1

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Estrone/Estradiol/Estriol/Progesterone (mg)/Capsule E1E2 0.063/E3 0.5/P 50 E1E2 0.063/E3 0.5/P 100 E1E2 0.1/E3 0.8/P 25 E1E2 0.125/E3 1/P 50 E1E2 0.25/E3 2/P 100 E1E2 0.375/E3 3/P 100 E1E2 0.5/E3 4/P 100 Estrone/Estradiol/Estriol/Progesterone/Testosterone (mg)/Capsule E1E2 0.125/E3 1/P 75/Te 5 E1E2 0.25/E3 2/P 100/Te 5 E1E2 0.375/E3 3/P 25/Te 1 E1E2 0.5/E3 4/P 50/Te 2.5 Estrone/Estradiol/Estriol/Progesterone/DHEA (mg)/Capsule E1E2 0.125/E3 1/P 100/D 10 E1E2 0.25/E3 2/P 75/D 2.5 Estrone/Estradiol/Estriol/Progesterone/DHEA/Test (mg)/Capsule E1E2 0.125/E3 1/P 100/D 2/Te 2.5 E1E2 0.25/E3 2/P 50/D 2.5/Te 5 Estrone (mg)/Capsule Estradiol (mg)/Capsule Estrone 0.5 Estradiol 0.5 Estrone 1 Estradiol 1 Estriol (mg)/Capsule Estradiol/Progesterone (mg)/Capsule Estriol 1 E2 0.25/P 50 Estriol 2 E2 0.25/P 100 Estriol 4 E2 0.5/P 100 Estriol/Progesterone (mg)/Capsule E3 1/P 100 E3 2/P 100 E3 4/P 100 Pregnenolone (mg)/Capsule Progesterone (mg)/Capsule Pregnenolone 25 Progesterone 5 Pregnenolone 50 Progesterone 25 Progesterone 50 Progesterone 75 Progesterone 100

Estradiol/Estriol/Progesterone (mg)/Capsule Testosterone (mg)/Capsule E2 0.25/E3 1/P 50 Testosterone 2 E2 0.5/E3 1/P 100 Testosterone 5 E2 0.5/E3 2/P 100 Testosterone 25 Testosterone 50 DHEA (mg)/Capsule Hydrocortisone (mg)/Capsule DHEA 5 Hydrocortisone 2.5 DHEA 10 Hydrocortisone 5 DHEA 15 Hydrocortisone 10 DHEA 25 DHEA 100 Thyroid We compound with T3 and T4 individually or combined as well as whole thyroid glandular. These are suspended in olive oil. Thyroid Glandular (mg)/Capsule T3/T4 (mcg)/Capsule Thyroid 60 (1 grain) Liothyronine 9/Levothyroxine 38 (~ 1 grain) Thyroid 120 (2 grain) Liothyronine 4.5/Levothyroxine 19 (~ ½ grain) DROPS Drops may be used orally, sublingually, or on the skin. Our drops are compounded with olive oil unless requested otherwise. Other vehicles we have used include glycerin/alcohol, glycerin, or other oils. Estradiol (mg)/Drop DHEA (mg)/Drop Estradiol 0.25 DHEA 1 Testosterone (mg)/Drop Progesterone (mg)/Drop Testosterone 2 Progesterone 50/8 drops Testosterone 5 GELS Gels compounded at Women’s International Pharmacy are in an alcohol base. Gels are used on the skin but are irritating to genital tissues.

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Estradiol (mg/gm) Gel Estriol (mg/gm) Gel Estradiol 1 Estriol 1 Estriol 2 Testosterone (mg/gm) Gel (Because of solubility, testosterone will only stay in solution up to 50mg/gm of gel.) Testosterone 3 Testosterone 5 Testosterone 25 Progesterone (mg/gm) Gel (The upper limit for progesterone is 50mg/gm of gel.) Progesterone 30 Progesterone 10 Estrone/Estradiol/Estriol (mg/gm) Gel Estradiol/Estriol/Testosterone (mg/gm) Gel E1E2 0.25/E3 0.75 E2 0.5/E3 2/Te 4 E1E2 0.5/E3 4 E2 0.5/E3 1/Te 2 Estradiol/Testosterone (mg/gm) Gel Estriol/Testosterone (mg/gm) Gel E2 1.75/Te 0.5 E3 0.5/Te 0.5 E2 1.75/Te 4 E3 0.5/Te 4 NON-ALCOHOL GELS The non-alcohol gels are similar to our alcohol-containing gels, but without alcohol. They are often prescribed for intra-vaginal use, or may also be used on the skin. The hormones are in a suspension and the gel appears cloudy. Estriol (mg/gm) N/A Gel Testosterone (mg/gm) N/A Gel Estriol 0.5 Testosterone 2 Estriol 1 Testosterone 6 Progesterone (mg/gm) N/A Gel Estriol/Testosterone (mg/gm) N/A Gel Progesterone 25 E3 0.5/Te 0.5 Progesterone 50 E3 0.5/Te 2 CREAMS Unless specified otherwise, we use our specially formulated cream as a base. It is a vanishing cream made with safflower oil. We also can offer a natural cream made with essential phospholipids. Ingredient lists are available on request.

Some alternative bases we have include, but are not limited to, Dermabase®, KY Jelly®, and Replens®. We can also incorporate hormones into other creams to meet a particular patient’s needs. Estrone/Estradiol/Estriol (mg/gm) Cream (Triest) E1E2 0.063/E3 0.5 E1E2 0.125/E3 1 E1E2 0.25/E3 2 Estrone/Estradiol/Estriol/Progesterone (mg/gm) Cream E1E2 0.063/E3 0.5/P 100 E1E2 0.375/E3 3/P 75 E1E2 0.125/E3 1/P 100 E1E2 0.5/E3 4/P 100 E1E2 0.25/E3 2/P 100 E1E2 0.25/E3 2/P 60 Estradiol/Progesterone (mg/gm) Cream Estradiol (mg/gm) Cream E2 0.5/P 100 Estradiol 1 Estradiol 0.5 Estriol/Progesterone (mg/gm) Cream Estriol (mg/gm) Cream E3 1/P 100 Estriol 0.5 Estriol 0.6 Estriol 1 Estriol 2 Estradiol/Estriol (mg/gm) Cream (Biest) Progesterone (mg/gm) Cream E2 0.25/E3 1 Progesterone 30 E2 0.5/E3 2 Progesterone 50 Progesterone 60 Progesterone 100 Estradiol/Estriol/Progesterone (mg/gm) Cream Testosterone (mg/gm) Cream E2 0.25/E3 1/P 100 Testosterone 2 E2 0.25/E3 2/P 100 Testosterone 5

Testosterone 10 Testosterone 20

Testosterone/Progesterone/Chrysin (mg/gm) Cream Te 50/P 5/Chrysin 25 LOZENGES Prescriptions compounded in lozenge form are dissolved in the mouth or under the tongue. Stevia and a variety of flavors may be added.

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Progesterone (mg)/Lozenge Testosterone (mg)/Lozenge Progesterone 100 Testosterone 5 Progesterone 200 Testosterone 50 Oxytocin (units)/Lozenge E1E2E3 (mg)/Lozenge Oxytocin 10 E1E2 0.1/E3 0.8 SUPPOSITORIES Hormones are incorporated into a suppository form with a fatty acid base. Estradiol/Progesterone (mg)/Suppository Estriol (mg)/Suppository Estradiol 0.125/P 20 Estriol 0.5 Progesterone (mg)/Suppository Estriol/Testosterone (mg)/Suppository Progesterone 50 Estriol 1/Testosterone 0.5 Progesterone 100 Progesterone 200 Progesterone 400 Progesterone 600 Our pharmacists are available to discuss individual needs and offer a variety of options for your patients.

Revised 11/2010

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The following tables have been compiled by Women’s International Pharmacy staff pharmacists to represent some of the more frequently prescribed regimens for women in menopause and some alternatives. The Women’s International Pharmacy logo is placed throughout the tables to signify the hormones and dosage forms Women’s International Pharmacy compounds.

This material is for informational purposes. It is not intended as a substitute for medical advice. Please consult a qualified health care professional for individual health and medical advice.

ORAL ESTROGENS

FEMALE HORMONE THERAPY OPTIONS

BIOIDENTICALDOSAGES AVAILABLE

DOSING REGIMEN COMMENTS/REFERENCES

Estradiol (E2) capsules(compounding pharmacies)

®

Any 0.25mg - 2mg once daily. Some may require twice daily dosing.

Hargrove J. Infertility & Reproductive Med Clinic North America 1995; 6(4):653-674.

Estriol (E3) capsules(compounding pharmacies)

Any 1mg - 8mg once daily or in divided doses.

Head K. Alt Med Rev; 1998; 3(2):101-113. Hudson T. Women’s Encyclopedia of Natural Medicine (Lincolnwood, IL: Keats) 1999:170.

®

Biestrogen (bi-est) capsules20% estradiol (E2),80% estriol (E3)(compounding pharmacies)

®

Any 1.25mg - 5mg once to twice daily

The 20:80 ratio may be altered to meet patient need.McKenna S. The Phytogenic Hormone Solution (NYC, NY: Villard Books) 2002:189-190.

Oral Estrogens

Triestrogen (tri-est, triple estrogen) capsules10% estrone (E1),10% estradiol (E2),80% estriol (E3)(compounding pharmacies)

®

AnyAlthough these ratios are commonly used and are based on the research done by Dr. Jonathan Wright, other formulas are available to accommodate individual needs. (Wright J, Morgenthaler J. Natural Hormone Replacement for Women over 45 (Petaluma, CA: Smart Publications) 1997:104-5,127.)

1.25mg - 2.5mg once to twice daily

Estrace®estradiol (E2) tablets(Warner Chilcott)

0.5mg, 1mg, 2mg

0.5mg - 2mg daily

Gynodiol®estradiol (E2) tablets(Fielding)

0.5mg, 1mg, 1.5mg, 2mg

0.5mg - 2mg daily Generics available.Micromedex Healthcare Series. DRUGDEX System. Greenwood Village, CO: Truven Health Analytics, 2013. https://www.micromedexsolutions.com/. Accessed February 28, 2014

Copyright © 2015, Women’s International Pharmacy Page 1

® = Compounded by Women’s International Pharmacy

Well absorbed orally. Micromedex Healthcare Series. DRUGDEX System. Greenwood Village, CO: Truven Health Analytics, 2013. https://www.micromedexsolutions.com/. Accessed February 28, 2014Generics Available

ORAL ESTROGENS

NON-BIOIDENTICALDOSAGES AVAILABLE


Cenestin®synthetic conjugated estrogens tablets(Duramed)

0.3mg, 0.45mg, 0.625mg,0.9mg, 1.25mg

0.3mg - 1.25mg daily Tablets contain a blend of nine synthetic estrogenic substances. (Drug Facts And Comparisons; 2007:223.)Only approved for the treatment of moderate to severe vasomotor symptoms associated with menopause and vulvar/vaginal atrophy (0.3mg only). (Drug Facts And Comparisons; 2007:223.)

Enjuvia® synthetic conjugated estrogens tablets(Duramed)

0.3mg, 0.45mg, 0.625mg, 0.9mg, 1.25mg

0.3mg – 1.25mg daily

Femtrace®estradiol acetate tablets(Warner Chilcott)

0.45mg, 0.9mg, 1.8mg

0.45mg – 1.8mg daily This product contains bioidentical estradiol, but is chemically bound to other substances.Only approved in the treatment of moderate to severe vasomotor symptoms associated with menopause. (Drug Facts and Comparisons; 2008:220a.)

Oral Estrogens

Menest®esterified estrogens tablets(Monarch)

0.3mg0.625mg1.25mg2.5mg

Tablets contain 75-85% sodium estrone sulfate and 6-15% sodium equilin sulfate, in such proportion that the total of these 2 components is not less than 90% of the total esterified estrogens content. (Drug Facts And Comparisons; 2008:221.)

0.3mg - 2.5mg daily

Ortho-Est®estropipate tablets formerly piperazine estrone sulfate(Women First Healthcare)

0.625mg1.25mg

0.625mg - 1.25mg daily

Premarin®conjugated equine estrogens tablets(CEE)(Wyeth)

0.3mg, 0.45mg,0.625mg, 0.9mg, 1.25mg

0.3mg - 1.25mg daily

Tablets contain a blend of ten synthetic estrogenic substances. (Drug Facts And Comparisons; 2006:223.)Only approved for the treatment of moderate to severe vasomotor symptoms associated with menopause and vulvar/vaginal atrophy (0.3mg only). (Drug Facts And Comparisons; 2007:224.)


Most studied estrogen replacement.

Tablets contain a mixture of conjugated equine (horse) estrogens. (Drug Facts And Comparisons; 2008:220b.)


This product is prepared from bioidentical estrone, but is chemically bound to other substances.Estropipate (R) [package insert]. Parsippany, NJ: Watson Pharmaceuticals; 2007.Generics Available.


ORAL PROGESTERONE



Progesterone(compounding pharmacies)

AnyOptimal absorption includes powder micronization and suspension in oil. (Hargrove J, Maxson W, et al. Am J OB/GYN, 1989; 161(4):948-951.)(Hargrove J. OB/GYN 73(4):606-612.)(Dr. Christiane Northrup, Women’s Bodies, Women’s Wisdom, (New York: Bantam Books) 2004:475.)

Prometrium®progesterone in peanut oil capsules(Solvay)

100mg200mg

Continuous: 100mg daily.Cyclic: 200mg - 300mg last 12-14 days of estrogen treatment each cycle.

Oral Progesterone; Progestins

Transient dizziness may occur.Contraindication: allergy to peanuts.PEPI Trials showed that Premarin® with Prometrium® produced more favorable lipid profiles than medroxyprogesterone plus Premarin®. (PEPI Trial Writing Group. JAMA, 1995; 273:199-208.) Generics available.

Continuous: 50mg twice daily or 100mg once to twice daily.Cyclic: 200-400mg daily for 12 days.

®

ORAL PROGESTINS



Amen®medroxyprogesterone acetate tablets(Carnick)

10mg Generics available.See Provera® for further comments and references.

Aygestin®norethindrone acetate tablets(Duramed)

5mg Cyclic: 5mg to 10mg daily for 5 to 10 days

Indicated for amenorrhea; abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology. (Drug Facts And Comparisons; 2008:231.). Generics available.

Cyclic: 10mg daily for 5-10 days

Curretab®medroxyprogesterone acetate tablets(Solvay)

10mg Cyclic: 10mg daily for 5-10 days

Generics available.See Provera® for further comments and references.

Cycrin®medroxyprogesterone acetate tablets(ESI Lederle)

2.5mg5mg10mg

Continuous: 2.5mg dailyCyclic: 5-10mg daily for 5-10 days

Generics available.

See Provera® for further comments and references.

Provera®medroxyprogesterone acetate tablets(MPA)(Pharmacia Upjohn)

2.5mg5mg10mg

Continuous: 2.5mg dailyCyclic: 5-10mg daily for 5-10 days

Indicated to prevent endometrial hyperplasia with concurrent estrogen use and secondary amenorrhea/abnormal uterine bleeding due to hormonal imbalance in the absence of organic pathology. PMS like side effects: insomnia, depression, nausea, thrombophlebitis and others. (Drug Facts And Comparisons; 2008:231.) Generics available.


ORAL ESTROGEN/PROGESTERONE COMBINATIONS



Estradiol (E2) with Progesterone(compounding pharmacies)

Any 0.5 - 2mg Estradiol with 50mg Progesterone twice daily or 100mg once to twice daily

See Oral Estrogen - Estradiol and Oral Progesterone comments and references.

Estriol (E3) with Progesterone(compounding pharmacies)

1 - 4mg Estriol with 50mg Progesterone twice daily or 100mg once to twice daily

Biestrogen (E2E3) with Progesterone(compounding pharmacies)

1.25 - 2.5mg Biestrogen with 50mg Progesterone twice daily or 100mg once to twice daily

Oral Estrogen/Progesterone Combinations

Triestrogen (E1E2E3) with Progesterone(compounding pharmacies)

See Oral Estrogen - Triestrogen and Oral Progesterone comments and references.

1.25 - 2.5mg Triestrogen with 50mg Progesterone twice daily or 100mg once to twice daily

See Oral Estrogen - Estriol and Oral Progesterone comments and references.


®

®

Any

®

See Oral Estrogen - Biestrogen and Oral Progesterone comments and references.

Any

®


Any

FemHRT®ethinyl estradiol (EE) and norethindrone acetate tablets(Warner Chilcott)

Combines synthetic estrogen and progestin for continuous administration.Micromedex Healthcare Series. DRUGDEX System. Greenwood Village, CO: Truven Health Analytics, 2013. https://www.micromedexsolutions.com/. Accessed February 28, 2014

2.5mcg (EE)/0.5mg norethindrone acetate5mcg (EE)/1mg norethindrone acetate

1 tablet daily

Prempro®conjugated equine estrogen (CEE) and medroxyprogesterone acetate tablets (MPA)(Wyeth)

The WHI Study (Women’s Health Initiative) indicated that the Prempro® group had a higher than normal incidence of blood clotting, breast cancer, and cardiovascular events. Because of the increased risks, the investigators stopped this portion of the study early. (WHI Writing Group. JAMA 2002; 288:321-333.)

Also see Oral Estrogen - Premarin® and Oral Progestin - Provera® comments.

0.3mg (CEE)/1.5mg (MPA)0.45mg (CEE)/1.5mg (MPA)0.625mg (CEE)/2.5mg (MPA)0.625mg (CEE)/5mg (MPA)

ORAL ESTROGEN/PROGESTIN COMBINATIONS



Activella®estradiol and norethindrone ac-etate tablets(Novo Nordisk)

0.5mg estradiol/0.1mg norethindroneacetate1mg estradiol/0.5mg norethindrone acetate

1 tablet daily Estradiol is bioidentical; progestin is not. Combines estrogen and progestin for continuous administration.

Generic available for higher strength. (Drug Facts and Comparisons; 2011:232a.)

Mimvey®estradiol and norethindrone ac-etate tablets(Teva)

Angeliq®estradiol and drospirenone tablets(Berlex)

Oral Estrogen/Progestin Combinations

Prefest®estradiol and norgestimate tablets(Duramed)

Estrogen is bioidentical; progestin is not.

Combines continuous estrogen with intermittent progestin to increase receptor sensitivity (J. Soc Gynecol Invest 1996; 3(5).)

Estradiol is bioidentical; progestin is not. Combines estrogen and progestin for continuous administration. (Drug Facts and Comparisons; 2011:232a.)

Estradiol is bioidentical; progestin is not. Combines estrogen and progestin for continuous administration. The lowest effective dose has not been determined. (Drug Facts and Comparisons; 2006:232.)


1mg estradiol/0.5mg norethindrone acetate

1 tablet daily

1mg estradiol0.5mg drospirenone

1 tablet daily

Biphasic:1mg estradiol (15 tablets)1mg estradiol with 0.09mg norgestimate(15 tablets)

1 tablet daily

1 tablet daily

Premphase®conjugated equine estrogen (CEE) and medroxyprogesterone acetate tablets (MPA)(Wyeth)

Also see Oral Estrogen - Premarin® and Oral Progestin - Provera® comments and references.

Biphasic:0.625mg (CEE)(14 tablets)0.625mg (CEE) with 5mg (MPA)(14 tablets)(28 day pack)

1 tablet daily


ORAL TESTOSTERONE



Testosterone(compounding pharmacies)

Any 2mg - 10mg once daily or in divided doses.

Testosterone may convert to estrogens in the body.Brownstein D. The Miracle of Natural Hormones, 3rd Edn. (W. Bloomfield, MI: Medical Alternatives Press) 2003:128.

Oral Testosterone; Estrogens/Testosterone ; SERMS


®

ORAL TESTOSTERONE



Methyltestosterone (MT)(some compounding pharmacies)

Any 0.25mg - 0.75mg daily

Rako S. The Hormone of Desire (New York: Harmony) 1996:113.

ORAL ESTROGEN/TESTOSTERONE COMBINATION



Covaryx®, Covaryx HS®esterified estrogens (E) with methyltestosterone (MT) tablets(Centrix)

1.25mg (E)/ 2.5mg (MT) (Covaryx®)0.625mg (E)/ 1.25mg (MT) (Covaryx HS®)

1 tablet daily (usually 21 days per month)

Increased risk of hepatotoxicity especially with oral methylated androgens. (Drug Facts And Comparisons; 2007:259.)Methyltestosterone is not readily converted to estrogen in the body. (Rako S. The Hormone of Desire (New York: Harmony) 1996:113.)

ORAL SERMS (SELECTIVE ESTROGEN RECEPTOR MODULATORS)



Evista®raloxifene tablets(Eli Lilly)

60mg 1 tablet daily Raloxifene‘s biological actions are mediated through estrogen receptor binding, resulting in activation of certain estrogenic pathways and blockade of others. (Drug Facts And Comparisons; 2008:225.)Increased risk for DVTs. (Drug Facts And Comparisons; 2008:225.)Increased incidence of hot flashes (29%). (Drug Facts And Comparisons; 2008:227.)

Although the selective estrogen receptor modulators are non-steroidal, they do act directly at hormone receptors and are indicated for the treatment and prevention of osteoporosis in postmenopausal women; particularly for women in which the administration of estrogen is contraindicated.


TOPICAL CREAMS/GELS – ESTROGEN-ONLY



Estradiol (E2)cream or gel(compounding pharmacies)

Any 0.5mg - 2mg once to twice daily

Lorrain et al. found Estradiol 0.75mg is equivalent to Premarin® 0.3mg with a starting dose of 1.5mg daily. (Lorrain et al Menopause Management Jan/Feb 1999: 11-15.)

SERMS; Topical Creams/Gels – Estrogens

Conley E. Safe Estrogen (Flint, MI: Vitality Press) 2003:43.


®

Estriol (E3)cream or gel(compounding pharmacies)

Any 2 to 5mg once daily or in divided doses.

®

Biestrogen (E2E3)cream or gel(compounding pharmacies)

1.25mg - 5mg once daily or in divided doses.

Collins J. What’s Your Menopause Type (Roseville, CA: Prima) 2000:293.

®

Any

Laux M, Conrad C. Natural Woman, Natural Menopause (New York: Harper Collins) 1998:116-117.Brownstein D. The Miracle of Natural Hormones 3rd edn (W. Bloomfield, MI: Medical Alternative Press) 2003:110.Also see Oral Estrogens - Triestrogen comments.

Triestrogen (E1E2E3)cream or gel(compounding pharmacies)

1.25mg - 2.5mg once to twice daily

®

Any

Divigel®estradiol topical gel(Upsher-Smith)

Apply daily to thigh

Apply gel to an area on thigh that measures 5 x 7 inches.Supplied in single-dose foil packets of 0.25, 0.5, and 1 gram, containing 0.25, 0.5, and 1 mg of estradiol, respectively. (Divigel® package insert.)

1mg/gram

Approved dose is 3.48 grams per day. Lowest effective dose not determined. (Drug Facts And Comparisons; 2009:224d.)Each 1.74 gram packet contains 4.35mg estradiol hemihydrate. (Drug Facts And Comparisons; 2009:224d.)

Estrasorb®estradiol hemihydrate topical emulsion(Graceway)

4.35mg per packet

Apply 2 packets once daily to both legs


ORAL SERMS (SELECTIVE ESTROGEN RECEPTOR MODULATORS) CONT.



Duaveeconjugated estrogens (CE) with bazedoxifene tablets (Pfizer)

0.45mg (CE)/20mg

1 tablet daily Indicated in women with a uterus for the treatment of moderate to severe vasomotor symptoms associated with menopause and the prevention of postmenopausal osteoporosis. Bazedoxifene is used, instead of progestin, to prevent endometrial hyperplasia that may result from estrogen-alone treatment. (Duavee [package insert]. Pfizer, New York, NY; 2013.)

TRANSDERMAL PATCHES – ESTROGEN-ONLY



Alora®estradiol (E2)(Watson)

One patch changed twice weekly

Patch may be cut to modify dose but is not recommended by the manufacturer. (Pharmacist Letter 1998; 14(7):140712.)

Topical Creams/Gels - Estrogen; Transdermal Patches – Estrogens;

Patch may be cut to modify dose but is not recommended by the manufacturer. (Pharmacist Letter 1998; 14(7):140712.)Generics available.


Climara®estradiol (E2)(Berlex)

One patch changed once weekly

Esclim®estradiol (E2)(Women First Healthcare)


Patch may be cut, but is not recommended by the manufacturer. (Pharmacist Letter 1998; 14(7):140712.)

Menostar®estradiol (E2)(Berlex)


Patch is a clear, dime-sized matrix type patch. Patch may be cut, but is not recommended by the manufacturer. (Pharmacist Letter 1998; 14(7):140712.)Approved for prevention of osteoporosis in postmenopausal women.

0.014mg

Approximately 1/3 the size of a regular Vivelle® patch. (Vivelle® patch replaced by Dot system.)Patch may be cut, but is not recommended by the manufacturer. (Pharmacist Letter 1998; 14(7):140712.)

Vivelle-Dot®estradiol (E2)(Novartis)

0.025 mg 0.0375 mg0.05 mg0.075 mg0.1mg

One Dot patch changed twice weekly

0.025, mg0.05, mg0.075 mg 0.1 mg

0.025 mg0.0375 mg 0.05 mg 0.06 mg0.075 mg 0.1 mg

0.025,0.0375 mg0.05 mg0.0750 mg0.1 mg


Evamist®estradiol transdermal spray(Ther-Rx Co.)

One spray once daily to forearm, may increase to two or three sprays

Transdermal alcohol spray.Supplied in a glass vial fitted with a metered dose pump encased in a plastic housing. Pump delivers 56 sprays of 90mcL after priming. (Evamist® package insert.)

1.53mg per spray

EstroGel®estradiol topical gel(Ascend Therapeutics, Inc.)

Apply 1 pump once daily to entire arm

Topical, colorless, alcohol gel.Supplied in a metered pump with a 0.06% concentration. Each 1.25 gram dose contains 0.75mg of estradiol. Pump delivers 64 metered doses. (Drug Facts And Comparisons; 2009:224d.)

0.75mg per pump

Topical, colorless, alcohol gel.Supplied in a metered pump with a 0.06% concentration. Each 0.87 gram dose contains 0.52mg of estradiol. Pump delivers 100 metered doses. (Elestrin® package insert.)

Elestrin®estradiol topical gel(Kenwood Therapeutics)

0.52mg per pump Apply 1 pump per day to the upper arm

TOPICAL CREAMS/GELS – ESTROGEN-ONLY CONT.



TOPICAL CREAMS / GELS - PROGESTERONE ONLY



Progesteronecream or gel(compounding pharmacies)

25mg - 100mg once to twice daily

Laux M, Conrad C. Natural Woman, Natural Menopause (New York: Harper Collins) 1998: 116-117.Brownstein D. The Miracle of Natural Hormones 3rd edn (W. Bloomfield, MI: Medical Alternative Press) 2003:99.

AnyCommon range: 20 – 100 mg/gram

®


TOPICAL CREAMS/GELS – ESTROGEN/PROGESTERONE COMBINATIONS



Estradiol (E2) with Progesteronecream or gel(compounding pharmacies)

Any 0.5mg - 2mg estradiol with 25mg - 100mg progesterone once to twice daily

See Topical Estrogen – Estradiol and Topical Progesterone comments.

Estriol (E3) with Progesteronecream or gel(compounding pharmacies)

1mg - 3mg estriol with 25mg - 100mg progesterone once to twice daily.

Biestrogen (E2E3) with Progesterone cream or gel(compounding pharmacies)

1.25mg - 2.5mg Biestrogen with 25mg - 100mg progesterone once to twice daily

Topical Creams/Gels – Progesterone; Topical Creams/Gels – Estrogen/Progesterone; Patches - Estrogen/Progestin

Triestrogen (E1E2E3) with Progesterone cream or gel(compounding pharmacies)

See Topical Estrogen – Triestrogen and Topical Progesterone comments.

1.25mg - 2.5mg Triestrogen with 25mg - 100mg progesterone once to twice daily

See Topical Estrogen – Estriol and Topical Progesterone comments.

®

®

Any

®

See Topical Estrogen – Biestrogen and Topical Progesterone comments.Any

®

Any

TRANSDERMAL PATCHES – ESTROGEN/PROGESTIN COMBINATIONS



Climara Pro®estradiol (E2) and levonorgestrel(Berlex)


Estradiol is bioidentical; progestin is not.Patch not recommended to be cut by manufacturer. (Pharmacist Letter 1998; 14(7):140712.)

Combi Patch®estradiol (E2) and norethindrone acetate(Novartis)


Estradiol is bioidentical; progestin is not.Patch may be cut but not recommended by manufacturer. (Pharmacist Letter 1998; 14(7):140712.)

0.045mg (E2)/ 0.015mg levonorgestrel

0.05mg (E2)/0.14mg norethindrone0.05mg (E2)/ 0.25mg norethindrone


VAGINAL ESTROGENS



Estradiol (E2) cream, non-alcohol gel, suppository, drops or clear capsule(compounding pharmacies)

Insert vaginally every night for 2 wks then 2-3 times weekly(anecdotal)

Cream and non-alcohol gel are dispensed with vaginal applicator calibrated in 1 gram increments up to 4 grams. Suppositories and clear capsules are dispensed with an applicator. Drops may be inserted with a clean finger.

Topical Creams/Gels - Testosterone ; Vaginal Estrogens

Gerbaldo D et al. Maturitas 1991; 13(4):269-274.Raz P, Stamm WE. NEJM 1993; 329(11): 753-756.


Estriol (E3) cream, non-alcohol gel, suppository, drops or clear capsule(compounding pharmacies)

0.5mg vaginally for 2 weeks then 0.5mg every 2-3 days

Estrace®estradiol vaginal cream(Warner-Chilcott)

Insert 2-4 grams every night for 2 wks then 1-2 grams for 1-2 wks then 1gram 3 times weekly

pH between 3.5-6.5.The 42.5 gram tube comes with a calibrated applicator in 1 gram increments up to 4 grams.(Drug Facts And Comparisons; 2009:224a.)

Releases estradiol at a mean rate of 7.5mcg/ 24 hours for up to 90 days. (Drug Facts And Comparisons; 2009:224a.)

Estring®estradiol vaginal silicone ring(Pharmacia)

Place 1 ring vaginally continuously for 3 months

Vagifem®estradiol hemihydrate vaginal tablet(Novo Nordisk)

Insert 1 tablet vaginally once daily for 2 weeks, then 1 tablet vaginally twice weekly

Approved only for atrophic vaginitis. Each tablet is contained in a disposable, single-use applicator.(Drug Facts And Comparisons; 2006:224.)

10.3mcg estradiol hemihydrate (equivalent to 10mcg estradiol)

Any

0.1mg/gm

2mg

®

®

Any


TOPICAL CREAMS/GELS - TESTOSTERONE-ONLY



Testosterone cream or gel(compounding pharmacies)

1mg - 20mg once daily or in divided doses.

2.5 to 5mg daily. (Laux M, Conrad C. Natural Woman, Natural Menopause (New York: Harper Collins) 1998:118.)2 to 10mg daily. (Brownstein D. The Miracle of Natural Hormones 3rd edn (W. Bloomfield, MI: Medical Alternative Press) 2003:128.)

®

Any

VAGINAL ESTROGENS



Premarin® creamconjugated equine estrogens (CEE)(Wyeth-Ayerst)

0.5-2 grams daily for 3 weeks with 1 week off

pH between 7.1 and 7.9; contains mineral oil. The 42.5 gram tube comes with or without an applicator. Can use 0.5gm twice weekly to treat painful intercourse. (Drug Facts And Comparisons; 2009:224b.)

0.625mg/gm

VAGINAL PROGESTERONE



ProgesteroneCream, non-alcohol gel, supposi-tory, or clear capsule(compounding pharmacies)

25mg - 100mg vaginally once to twice daily

50mg vaginal suppository twice daily. (The Merck Manual of Diagnosis and Therapy Sec. 18, Ch. 245.)

Vaginal Estrogens; Vaginal Progesterone


Crinone® / Prochieve®progesterone vaginal gel(Columbia Lab)

Contents of 1 applicator vaginally once to twice daily

Gel contains mineral oil.Gel coats the vaginal mucosa to provide long lasting release of progesterone, Supplied in a 4 or 8% concentration in disposable, single-use applicators. Each 1.125 grams of gel delivers either 45mg or 90mg of progesterone.(Drug Facts And Comparisons; 2006:230.)

Indicated to support embryo implantation and early pregnancy.Each insert is packed individually in a sealed foil pouch and supplied with disposable applicators.(Enodmetrin® package insert.)

Endometrin®Progesterone vaginal insert(Ferring Pharmaceuticals)

Insert 1 vaginally two or three times daily

45mg per applicator90mg per applicator

®

AnyCommon range: 20 – 100 mg/gram

100mg


Contains 12.4mg Estradiol acetate that releases 0.05mg per day for 3 months.Contains 24.8mg Estradiol acetate that releases 0.1mg per day for 3 months.(Drug Facts And Comparisons; 2009:224a.)

Femring®estradiol acetate vaginal ring(Galen)

0.05mg/day0.1mg/day

Place 1 ring vaginally continuously for 3 months

INJECTABLES / PELLETS



Injectables


Progesterone in sesame oil(various, e.g., APP, Watson)

5 to 10 mg intramuscularly daily for 6 to 8 days

Has been used for amenorrhea or abnormal uterine bleeding. (Drug Facts and Comparisons; 2008:230.)

50mg/ml

Testosterone blood levels peak at 1 month then sustained in normal range for 4 to 6 months. Requires surgical incision for insertions; pellets may extrude spontaneously. (Bhasin S, et al. Journal of Clinical Endocrinology & Metabolism Vol 91, issue 6; 1995-2010.)

Testosterone pellets(some compounding pharmacies)

Pellets implanted subcutaneously

Various



Premarin IV®conjugated equine estrogens (CEE)(Wyeth-Ayerst)

25 mg intravenously or intramuscularly repeat in 6 to 12 hours if necessary

Used for abnormal uterine bleeding. (Drug Facts and Comparisons; 2008:220b.)

Depo-Estradiol®estradiol cypionate*in cottonseed oil(Pharmacia)

1 to 5 mg intramuscularly every 3 to 4 weeks

Short-term cyclical use for moderate to severe vasomotor symptoms and vulva/vaginal atrophy. Taper or discontinue medication at 3 to 6 month intervals. (Drug Facts and Comparisons; 2009:224a.)

5mg/ml

25mg


Estradiol pellets(some compounding pharmacies)

Any Pellets implanted subcutaneously

“Ten women with estrogen deficiency symptoms because of premature menopause, gonadal dysgenesis, or surgical menopause received subcutaneous implants consisting of 25-75 mg estradiol with or without 75 mg testosterone. Clinically, all patients had symptomatic improvement within 24-48 hours.” Kapetanakis E, Dmowski WP, Auletta F, Scommegna A.Int J Gynaecol obstet. 1982 Oct;20(5):387-99. Endocrine and clinical effects of estradiol and testosterone pellets used in long-term replacement therapy.


To reduce preterm birth in a single pregnancy for women who have a history of preterm birth in single pregnancy. Begin between week 16 0 days and week 20 6 days gestation. Continue until week 37 0 days gestation or delivery. (Drug Facts and Comparisons; 2011:231.)

Makena®Hydroxyprogesterone caproate* in castor oil(Ther-Rx)

250mg intramuscularly once weekly

250mg/ml

*Bioidentical hormones may be bound to various esters to increase the length of activity. Only when the ester is removed from the hormone by the body does the hormone become bioidentical.


Delestrogen®estradiol valerate* in sesame oil(JHP)

10 to 20 mg intramuscularly every 4 weeks

For moderate to severe vasomotor symptoms and vulva/vaginal atrophy associated with menopause. Attempts to discontinue medication at 3 to 6 month intervals. (Drug Facts and Comparisons; 2008:220a.)Generics available.

Injectables


10mg/ml20mg/ml 40mg/ml


Copyright © September 2015, Women’s International Pharmacy. This article may not be reproduced without the permission of Women’s International Pharmacy



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