Subject: Hormone Replacement

Status	Drug	PR-B/D	PR	PR-QL	PR-AL	ST	M EX‡	TOC§
Oral Estrogens - Combinations
C	estradiol
C	estradiol & norethindrone acetate
C	estropipate				X
C	Gynodiol® (estradiol)
C	Ortho-est®(estropipate)				X
C	Premarin®  (conjugated estrogens)				X
C	Premphase®  (conjugated estrogens- mpa)				X
C	Prempro®  (conjugated estrogens- mpa)				X
NC	Activella®  (estradiol & norethindrone acetate)						X
NC	Angeliq®  (estradiol & drospirenone)						X
NC	Cenestin®  (synthetic conjugated estrogens)						X
NC	Enjuvia®  (synthetic conjugated estrogens)						X
NC	Estrace®  (estradiol)						X
NC	FemHRT®  (norethindrone acetate-ethinyl estradiol)						X
NC	Femtrace®  (estradiol)						X
NC	Menest®  (esterified estrogens)				X		X
NC	Ogen®  (estropipate)				X		X
NC	Prefest®  (estradiol-norgestimate)						X
Dermatologic and Vaginal Products
C	estradiol patch			X
C	Estrace®  (estradiol vaginal cream)
C	Evamist®  (estradiol transdermal spray)
NC	Alora®  (estradiol patch)			X			X
NC	Climara Pro®  (estradiol/levonorgestrel patch)			X			X
NC	Climara®  (estradiol patch)			X			X
NC	Combipatch®  (estradiol/norethindrone patch)			X			X
NC	Divigel®  (estradiol patch)						X
NC	Elestrin®  (estradiol gel)						X
NC	Esclim®  (estradiol patch)			X			X
NC	Estraderm®  (estradiol patch)			X			X
NC	Estrasorb®  (estradiol hemihydrate lotion)						X
NC	Estring®  (estradiol vaginal ring)						X
NC	Estrogel®  (estradiol gel)						X
NC	Femring®  (estradiol transdermal spray)						X
NC	Menostar®  (estradiol patch)			X			X
NC	Premarin® vag cream  (estradiol vag cream)						X
NC	Vagifem®  (estradiol vaginal tablet)						X
NC	Vivelle®  (estradiol patch)			X			X
NC	Vivelle-Dot®  (estradiol patch)			X			X

Policy:

1. Precertification Criteria

Under some plans, including plans that use an open or closed formulary Alora, Climara Pro, Climara, Combipatch, Esclim, Estraderm, estropipiate, Menest, Menostar, Ogen, Ortho-est, Premarin, Premphase,  Prempro, Vivelle, Vivelle-Dot and generic estradiol patch are subject to precertification.  If precertification requirements apply Aetna considers Alora, Climara Pro, Climara, Combipatch, Esclim, Estraderm, estropipiate, Menest, menostar, Ogen, Ortho-est, Premarin, Premphase, Prempro, Vivelle, Vivelle-Dot and generic estraiol patch to be medically necessary for those members who meet the following percertification criteria:

For Alora, Climara Pro, Climara, Combipatch, Esclim, Estraderm, Menostar, Vivelle,  Vivelle-Dot and generic estradiol patch


 

A. Quantity limits: Hormone Replacement

According to the manufacturer, the transdermal hormone replacement agents Alora, Climara Pro, Climara, Combipatch, Esclim, Estraderm, Menostar, Vivelle, Vivelle-Dot and generic estradiol patch can be dosed at the interval(s) as indicated in the table below. A quantity of each drug will be considered medically necessary as indicated in the table below: 


Drug	Maximum Daily Dose/ Dosing Interval	Dosage Strength	Quantity Limits
estradiol	Once weekly	0.025mg, 0.05mg, 0.075mg, 0.1mg	Up to 4 patches in 28 days
Vivelle	Twice weekly	0.05mg, 0.1mg	Up to 8 patches in 28 days
Vivelle-Dot	Twice weekly	0.025mg, 0.037mg, 0.05mg, 0.075mg, 0.1mg	Up to 8 patches in 28 days
Estraderm	Twice weekly	.05mg, 0.1mg	Up to 8 patches in 28 days
estradiol, Climara	Once weekly	0.025mg, 0.0375mg, 0.05mg, 0.06mg, 0.075mg, 0.1mg	Up to 4 patches in 28 days
Climara-Pro	Once weekly	0.045mg/0.015mg	Up to 4 patches in 28 days
Alora	Twice weekly	0.025mg, 0.05mg, 0.075mg, 0.1mg	Up to 8 patches in 28 days
Esclim	Twice weekly	0.025mg, 0.037mg, 0.05mg, 0.075mg, 0.1mg	Up to 8 patches in 28 days
Combipatch	Twice weekly	0.05mg/0.025mg, 0.05mg/0.14mg	Up to 8 patches in 28 days
Menostar	Once weekly	14mcg	Up to 4 patches in 28 days





For coverage of additional quantities, a member's treating physician must request prior authorization through the Aetna Pharmacy Management Precertification Unit.  Additional quantities of transdermal hormone replacement agents Vivelle, Vivelle-Dot, Estraderm, estradiol, Climara, Alora, Esclim, Menostar, Climara Pro and Combipatch will be considered medically necessary for those members who meet the following criteria:

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

For estropipiate, Menest, Ogen, Ortho-est, Premarin, Premphase and Prempro (members greater than or equal to 65 years of age):

A documented:

A.   Member has tried and failed the alternative drug - oral estradiol --  that is appropriate in the elderly to treat the condition. OR
B.  The physician indicates the drug is medically necessary




2. Medical Exception Criteria

Activella, Alora, Angeliq, Cenestin, Climara, Climara Pro, Combipatch, Divigel, Elestrin, Enjuvia, Esclim, Estrace, Estraderm, Estrasorb, Estring, Estrogel, FemHRT, Femring, Femtrace, Menest, Menostar, Ogen, Prefest, Premarin vag cream, Vagifem, Vivelle and Vivelle-Dot currently are Not Covered Part D drugs under the Aetna Medicare Prescription Drug Plan.* Therefore, they 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 Activella, Alora, Angeliq, Cenestin, Climara, Climara Pro, Combipatch, Divigel, Elestrin, Enjuvia, Esclim, Estrace, Estraderm, Estrasorb, Estring, Estrogel, FemHRT, Femring, Femtrace, Menest, Menostar, Ogen, Prefest, Premarin vag cream, Vagifem, Vivelle and Vivelle-Dot to be medically necessary for those members who meet the following criteria:

For Activella, Angeliq, Cenestin, Enjuvia, Estrace, FemHRT, FemHRT low, Femtrace, Menest, Ogen and Prefest

A documented:

• Contraindication to one preferred oral estrogen or oral combination agent indicated for the member's condition OR
• Intolerance to one preferred oral estrogen or oral combination agent indicated for the member's condition OR
• Allergy to one preferred oral estrogen or oral combination agent indicated for the member's condition OR
• Failure of an adequate trial of one month of one preferred oral estrogen or oral combination agent indicated for the member's condition

For Alora, Climara, Divigel, Elestrin, Esclim, Estraderm, Estrogel, Estrasorb, Estring, Femring, Menostar, Premarin vag cream, Vagifem, Vivelle and Vivelle-Dot

A documented:

• Contraindication to one preferred dermatologic or vaginal product indicated for the member's condition OR
• Intolerance to one preferred dermatologic or vaginal product indicated for the member's condition OR
• Allergy to one preferred dermatologic or vaginal product indicated for the member's condition OR
• Failure of an adequate trial of one month of one preferred dermatologic or vaginal product indicated for the member's condition

For Climara Pro and Combipatch

• Patient has an intact uterus and has tried and failed a preferred alternative estrogen-only transdermal in combination with an oral progestin and is intolerant to the oral progestin.

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.

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.

March 30, 2009