AllCare CCO - Prior Authorization Criteria Summary: Criteria number: 020.1 Criteria title: HRT Date of origin: 12/14/2012 Classification: Class Specific Date of Last Review: 01/22/2019 Drug Class: Hormone Replacement Therapy Date of Next Review: 01/21/2021 References: ● Oregon Health Authority, Department of Medical Assistance, OAR 410-120-0250 (3): ● Oregon Medicaid Pharmaceutical Services Prior Authorization Criteria : ● Beral V, Bull D, Reeves G. Endometrial cancer and hormone replacement therapy in the million women study. Lancet 2005 Apr 30;365(9470):1543: ● Stuenkel C, Davis R, Gompel A, et al. Treatment of symptoms of the menopause: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2015; 100(11):3975-4011. : ● The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017; 12(7):728-753: ● Williams, J., & Nieuwsma, J. (2018). Treatment of menopausal symptoms with hormone therapy. William F Crowley, Jr, MD (Ed.), UpToDate. Retrieved December 19, 2018: ● Intrarosa Label In: Drugs@FDA. United States Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208470s000lbl.pdf: ● Archer D, Labrie F, Bouchard C. et al. Treatment of pain at sexual activity (dyspareunia) with intravaginal dehydroepiandrosterone (prasterone). Menopause. 2015;22(9): 950-963. : ● Labrie F, Archer D, Kolutn W. et al. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause. 2016;23(3):243-256.: ● Menopause. In DynaMed. EBSCO Publishing. Updated 07/06/17. From: http://web.ebscohost.com.liboff.ohsu.edu/dynamed : ● Pinkerton J, Utian W, Constantine G, et al. Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrognes: a randomized controlled trial. Menopause. 2009; 16(6):1116-1124: ● Duavee Label In: Drugs@FDA. United States Food and Drug Administration.

x FDA approved indication: Purpose: To define the process and coverage for hormone replacement therapy Clinical Rationale: There is a lack of efficacy evidence for long term use of HRT in post-menopausal women. Safety risks increase with chronic use, including an increase in breast cancer and breast cancer mortality associated with 3 to 5 years use. Long term use of estrogen-only replacement therapy increases risk of endometrial cancer. Cardiovascular risks including stroke are associated with HRT and estrogen-only therapy. Contraindications to HRT include a history of breast cancer, CHD, a previous venous thromboembolic event or stroke, active liver disease, unexplained vaginal bleeding, high-risk endometrial cancer, or transient ischemic attack

Policy: Cover non-preferred estrogen tablets, creams or patches for members who have tried/failed a formulary systemic hormone replacement therapy. Cover other non-preferred formulations for members who have tried/failed two formulary systemic hormone replacement therapies including the generic estradiol patch. Agents included in criteria: estradiol patch Formulary, Preferred estradiol tablet Formulary, Preferred estradiol cream Formulary, Non-preferred estradiol vaginal (Vagifem) tablet Formulary, Preferred estradiol ring (Estring) Formulary, Preferred estropipate tablet Formulary, Preferred conj. Estrogen tablet (Premarin) Formulary, Non-preferred conj. estrogen cream (Premarin) Formulary, Non-preferred progesterone tablet progesterone tablet medroxyprogesterone tablet Formulary, Preferred norethindrone tablet Formulary, Preferred estradiol/norethindrone tablet Formulary, Preferred estradiol/norethindrone patch (Combipatch) Formulary, Preferred estrogen/medroxyprogesterone (Prempro) tablet Formulary, Non-preferred prasterone (Intrarosa) Formulary, Non-preferred conj. Estrogen/bazedoifene (Duavee) Formulary, Non-preferred ospemifene (Osphena) Formulary, Non-preferred Approval length: Up to Up to 5 years x Approval criteria for Hormone Replacement Therapy: Met Not Met Criteria #1: Does the member have a covered diagnosis of hormone replacement Go to #4 Go to #2 therapy for symptoms of menopause Criteria #2: Is the request for prasterone or ospemifene for a covered diagonsis of Go to #4 Go to #3 atrophic vaginitis or dyspareunia related to menopause

Criteria #3: Is the requested drug FDA-approved for the treatment of the Go to #4 Deny submitted and/or comorbid diagnoses OR is supported by information from the appropriate compendia of current literature

Criteria #4: Does the member have a documented trial/failure of a preferred Go to #5 Deny estrogen or estrogen/progestin product Criteria #5: Is the member under 65 years old Approve x5 years or Go to #6 until 65th birthday

Criteria #6: Does the provider acknowledge that the drug is labeled as a high risk Approve x1 year Deny medication in patients 65 years and older x Reviewed and approved by: AllCare CCO P&T Committee Date: 08/24/2017