Category: Hormonal Agents, Stimulant/ Replacement/ Modifying (Sex Hormones/ Modifiers)

Class: Estrogens

Status	Drug	PR-B/D	PR	PR-QL	PR-AL	ST	M EX	TOC	NSO
Oral-Estrogen Replacement
C	ESTRADIOL
C	ESTROPIPATE				X
C	GYNODIOL (ESTRADIOL )
C	ORTHO-EST (ESTROPIPATE)				X
C	CENESTIN  (ESTROGENS, CONJUGATED SYNTHETIC A)
C	ENJUVIA  (ESTROGENS, CONJUGATED SYNTHETIC B)
C	FEMTRACE  (ESTRADIOL ACETATE)
C	MENEST  (ESTERIFIED ESTROGENS)				X
C	PREMARIN  (ESTROGENS, CONJUGATED)				X
NC	ESTRACE  (ESTRADIOL)						X
NC	OGEN  (ESTROPIPATE)				X		X
Oral-Estrogen-Progestin Replacement-Combination
C	ESTRADIOL/NORETHINDRONE Acetate
C	ACTIVELLA  (ESTRADIOL & NORETHINDRONE ACETATE 0.5-0.1 MG)
C	FEMHRT 1/5 & Low  (NORETHINDRONE ACETATE-ETHINYL ESTRADIOL)
C	PREFEST  (ESTRADIOL TAB /ESTRAD-NORGESTIMATE TAB )
C	PREMPHASE  (CONJugated EST / CONJugated EST-MEDROXYPRO AC TAB )				X
C	PREMPRO  (CONJUGATED ESTROGEN-MEDROXYPROGEST ACETATE)				X
NC	ACTIVELLA  (ESTRADIOL & NORETHINDRONE ACETATE1-0.5 MG)						X
NC	ANGELIQ  (DROSPIRENONE-ESTRADIOL)						X
Transdermal-Estrogen Replacement
C	ESTRADIOL TD PATCH WEEKLY			X
C	ALORA  (ESTRADIOL TD PATCH BIWEEKLY)			X
C	DIVIGEL  (ESTRADIOL TD GEL )
C	ESTRADERM  (ESTRADIOL TD PATCH BIWEEKLY )			X
C	ESTRASORB  (ESTRADIOL TRANSDERMAL EMULSION )
C	ESTROGEL  (ESTRADIOL GEL METERED-DOSE PUMP)
C	EVAMIST  (ESTRADIOL TRANSDERMAL SPRAY)
C	MENOSTAR  (ESTRADIOL TD PATCH WEEKLY )			X
C	VIVELLE-DOT  (ESTRADIOL TD PATCH BIWEEKLY )			X
NC	CLIMARA  (ESTRADIOL TD PATCH WEEKLY)			X			X
NC	ELESTRIN  (ESTRADIOL GEL METERED-DOSE PUMP)						X
Transdermal-Estrogen Replacement-combination
C	CLIMARA PRO  (ESTRADIOL-LEVONORGESTREL TD PATCH WEEKLY)			X
C	COMBIPATCH  (ESTRADIOL-NORETHINDRONE ACE TD PTTW)			X
Vaginal-Estrogen Replacement
C	ESTRACE  (ESTRADIOL vaginal cream)
C	ESTRING  (ESTRADIOL VAGINAL RING)
C	FEMRING  (ESTRADIOL ACETATE VAGINAL RING)
C	PREMARIN W/APPLICATOR  (ESTROGENS, CONJUGATED VAGINAL CREAM)
C	VAGIFEM  (ESTRADIOL VAGINAL tab)
Injectable-Estrogen Replacement
C	ESTRADIOL VALERATE IM in oil
C	DEPO-ESTRADIOL  (ESTRADIOL CYPIONATE IM IN OIL)
NC	DELESTROGEN  (ESTRADIOL VALERATE IM IN OIL)						X

Policy:

1. Precertification Criteria:

Under some plans, including plans that use an open or closed formulary, precertifcation criteria may apply.  If precertification requirements apply Aetna considers the drugs below to be medically necessary for those members who meet the following precertification criteria:

1. Age Limitations

According to the manufacturer labeling or dosing safety guidelines Aetna considers the following age criteria medically necessary for the drugs listed below.

For estropipate, ortho-est, Menest, Ogen, Premarin, Premphase, Prempro

• Covered for members less than 65 years of age.
  
  
2. Age Limitations Medical Exceptions

If it is medically necessary for a member to be treated initially with one of these medications subject to age limitation, the member, a person appointed to manage the member’s care, or the member’s treating physician may contact the Aetna Pharmacy Management Precertification Unit at 1-800-414-2386 to request coverage as a medical exception. Aetna considers these drugs to be medically necessary for those members who meet the criteria specified below.

 For estropipate, ortho-est, Menest, Ogen, Premarin, Premphase, Prempro

• If member is greater than or equal to 65 years of age they must try and fail an alternative drug to treat the condition that is appropriate in the elderly such as oral estradiol OR The physician indicates the drug is medically necessary
  
  
3. Precertification Coverage Duration

Aetna considers the following Maximum length of approval for the drug(s) that meet any/all precertification criteria that applies.

Through End of Plan Contract Year.

2. Quantity Limits




According to the manufacturer labeling, a quantity of each drug will be considered medically necessary as indicated in the table below:

Drug Name	Dosage Form	Strength	Qty	Day(s)
ALORA	BIWEEKLY TD PATCH	0.025MG/24HR; 0.05MG/24HR; 0.075MG/24HR ; 0.10MG/24HR	8	Per 28 days	Max Daily Dose One patch twice weekly
generics; CLIMARA	WEEKLY TD PATCH	0.025MG/24HR; 0.0375MG/24HR; 0.05MG/24HR; 0.06MG/24HR; 0.075MG/24HR; 0.10MG/24HR	4	Per 28 days	Max Daily Dose One patch once weekly
CLIMARA PRO	WEEKLY TD PATCH	0.045-0.015 MG/DAY	4	Per 28 days	Max Daily Dose One patch once weekly
COMBIPATCH	BIWEEKLY TD PATCH	0.05-0.14 MG/DAY; 0.05-0.25MG/DAY	8	Per 28 days	Max Daily Dose One patch twice weekly
ESTRADERM	BIWEEKLY TD PATCH	0.05 MG/24HR; 0.10 MG/24HR	8	Per 28 days	Max Daily Dose One patch twice weekly
MENOSTAR	WEEKLY TD PATCH	14 MCG/24HR	4	Per 28 days	Max Daily Dose One patch  weekly
VIVELLE-DOT	BIWEEKLY TD PATCH	0.025 MG/24HR; 0.0375 MG/24HR; 0.05MG/24HR; 0.075 MG/24HR; 0.10 MG/24HR	8	Per 28 days	Max Daily Dose One patch twice weekly





Quantity Limit Exceptions

For coverage of additional quantities, the member, a person appointed to manage the member’s care, or the member's treating physician may contact the Aetna Pharmacy Management Precertification Unit at 1-800-414-2386. Additional quantities will be considered medically necessary for those members who meet the following criteria.

• Member requires a dose that includes half-patch dosing (only matrix patches) OR
• Member's physician provides documentation (controlled clinical trial) from the peer-reviewed medical literature for use of a higher dose

Quantity Limit Coverage Duration

Aetna considers the following Maximum length of approval for the drug(s) that meet quantity limits criteria.
 
Through End of Plan Contract Year.




3. Not Covered Drug Criteria




Not Covered Part D drugs under the Aetna Medicare Prescription Drug Plan  are excluded from coverage for members enrolled in prescription drug benefits plans that use a closed formulary, unless a medical exception is granted.  Aetna considers the drugs below to be medically necessary for those members who meet the following criteria.

For All Not Covered (NC) Drugs

• Contraindication or Intolerance or Allergy or Failure of one month each of four covered(C) alternatives.
  
  
1. Not Covered Drug Coverage Duration




Aetna considers the following Maximum length of approval for the drug(s) that meet criteria for not covered drugs.

Through End of Plan Contract Year.

Place of Service:

Outpatient

The above policy is based on the following references:

1. DrugPoints® System ( www.statref.com) Thomson Micromedex, Greenwood Village, CO. Updated periodically.
2. AHFS Drug Information® with AHFSfirstReleases®. ( www.statref.com), American Society Of Health-System Pharmacists®, Bethesda, MD. Updated periodically.
3. DRUGDEX® System [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.
4. Drug Facts and Comparisons on-line. (www.drugfacts.com), Wolters Kluwer Health, St. Louis, MO. Updated periodically.
5. PDR® Electronic Library™ [Internet database]. Greenwood Village, Colo: Thomson Micromedex. Updated periodically.
6. Clinical Pharmacology [Internet database]. Gold Standard Inc. Tampa, FL. Updated periodically.
7. Fick DM, Cooper JW, Wade WE, et al.  Updating the Beers criteria for potentially inappropriate medication use in older adults.  Arch Intern Med. 2003;163:2716-24.
8. Zahn C, Sangl J, Bierman AS, et al.  Potentially inappropriate medication use in the community-dwelling elderly.  JAMA.  2001;286:2823-29.
9. Long CY, Liu CM, Hsu SC, et al. A randomized comparative study of the effects of oral and topical estrogen therapy on the vaginal vascularization and sexual function in hysterectomized postmenopausal women. Menopause. 2006 Sep-Oct;13(5):737-43.
10. Simon JA; ESTRASORB Study Group. Estradiol in micellar nanoparticles: the efficacy and safety of a novel transdermal drug-delivery technology in the management of moderate to severe vasomotor symptoms. Menopause. 2006;13(2):222-31.
11. Sare GM, Gray LJ, Bath PM. Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis. Eur Heart J. 2008 Jul 3.
12. Abramowicz M, ed. Hormone Replacement Therapy. The Medical Letter on Drugs and Therapeutics. 2002; 44(1138): 78.
13. Rossouw JE. Writing  Group for the Women’s Health Initiative Investigators. Risks and Benefits of Estrogen Plus Progest in Healthy Postmenopausal Women: Principal Results from the Women’s Health Initiative Randomized Controlled Trial. JAMA. July 2002; 288: 321-333.
14. Hulley S Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA Jul-2002; 288(1): 58-66.
15. Hlatky MA Quality-of-life and depressive symptoms in postmenopausal women after receiving hormone therapy: results from the Heart and Estrogen/Progestin Replacement Study (HERS) trial. JAMA Feb-2002; 287(5): 591-7.FDA Talk Paper: http://www.fda.gov/bbs/topics/ANSWERS/2003/ANS01210.html FDA Revises Findings on Estrogen/Androgen Combination Products in the Treatment of Hot Flashes. April 10,2003
16. American College of Obstetricians and Gynecologists. Position Statement to Women’s Health Initiative Study Results by the American College of Obstetricians and Gynecologists. August 9, 2002
17. The North American Menopause Society. Report from the NAMS Advisory Panel on Postmenopausal Hormonal Therapy. Available at www.menopause.org/news.html/#advisory. Published Oct 2002.
18. American Heart Association. Q&A About Hormone Replacement Therapy. Available at http://216.185.112.5/presenter.jhtml?identifier=3004068 Published October 2002.
19. Sadovsky R. Recent analysis of hormone replacment therapy. Available at: www.aafp.org/afp/20000101/tips/17.html. Published June 2002.
20. WHI Findings Summary Estrogen plus Progestin Effects on Bone Density and the Risk of Fractures found http://www.whi.org/findings/summary_bone.asp JAMA 290(13)October  2003, 1729-1738.
21. Warren MP. A comparative review of the risks and benefits of hormone replacement therapy regimens. Am J Obstet Gynecol. 2004 Apri; 190(4): 1141-67
22. Sare GM, Gray LJ, Bath PM. Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis. Eur Heart J. 2008 Jul 3.
23. AACE Menopause Guidelines Revision Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause. Endocr Pract May-June 2006;315-37.

Property of Aetna Inc. All rights reserved. Pharmacy Clinical Policy Bulletins are developed by Aetna to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. This Clinical Policy Bulletin contains only a partial, general description of plan or program benefits and does not constitute a contract. Aetna does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Aetna or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. This Clinical Policy Bulletin may be updated and therefore is subject to change.

Original Policy Date: January 01, 2010

Effective Date: January 01, 2010