DUAVEE, Conjugated Estrogens-Bazedoxifene Form

Conjugated estrogens/bazedoxifene (Duavee®) is a combination of conjugated equine estrogens and an estrogen agonist/antagonist. The pairing of conjugated estrogens with bazedoxifene produces a composite effect that is specific to each target tissue. The bazedoxifene component reduces the risk of endometrial hyperplasia that can occur with the conjugated estrogens component. FDA Approved Indication(s) Duavee is indicated in women with a uterus for: • Treatment of moderate-to-severe vasomotor symptoms associated with menopause. • Prevention of postmenopausal osteoporosis.
Limitation(s) of use:
• Duavee should be used for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary. • When prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk of osteoporosis and non-estrogen medication should be carefully considered. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Duavee is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Vasomotor Symptoms (must meet all):

1. Diagnosis of vasomotor symptoms associated with menopause;
   2. Member has not undergone a hysterectomy;
   3. Failure of 2 formulary estrogen products (not contraceptives, see Appendix B), unless contraindicated or clinically significant adverse effects are experienced;

2. Dose does not exceed both of the following (a and b):
   a. 0.45 mg conjugated estrogens/20 mg bazedoxifene per day;
   b. 1 tablet per day.
   Approval duration: 6 months Page 1 of 7

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   Conjugated Estrogens/Bazedoxifene B. Osteoporosis (must meet all):

3. Prescribed for the prevention of postmenopausal osteoporosis;
   2. Member has not undergone a hysterectomy;
   3. Failure of a 12-month trial of an oral bisphosphonate (see Appendix B; generic alendronate is preferred) at up to maximally indicated doses, unless contraindicated or clinically significant adverse effects are experienced;
4. Failure of a 12-month trial of raloxifene, unless contraindicated or clinically significant adverse effects are experienced;
5. Dose does not exceed both of the following (a and b):
   a. 0.45 mg conjugated estrogens/20 mg bazedoxifene per day;
   b. 1 tablet per day.
   Approval duration: 6 months C. Other diagnoses/indications (must meet 1 or 2):
6. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or
   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid. II. Continued Therapy A. All Indications in Section 1 (must meet all):

7. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);

   2. Member is responding positively to therapy;
   3. If request is for a dose increase, new dose does not exceed both of the following (a and b): a. 0.45 mg conjugated estrogens/20 mg bazedoxifene per day;
      b. 1 tablet per day Approval duration: 12 months Page 2 of 7

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   Conjugated Estrogens/Bazedoxifene B. Other diagnoses/indications (must meet 1 or 2):

8. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: HIM.PA.33 for health insurance marketplace and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: HIM.PA.103 for health insurance marketplace and CP.PMN.16 for Medicaid; or

   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid. III. Diagnoses/Indications for which coverage is NOT authorized:
      A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policy – HIM.PA.154 for health insurance marketplace and CP.PMN.53 for Medicaid or evidence of coverage documents. IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration WHI: Women's Health Initiative Appendix B: Therapeutic Alternatives
      This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent and may require prior authorization.
      Drug Name Dosing Regimen Dose Limit/ Maximum Dose Estrogen Products estradiol (Alora®, Climara®, Divigel®, Elestrin®, Estrace®, EstroGel®, Evamist®, Menostar®, Minivelle®, Vivelle Dot®) Menest® (esterified estrogens) Premarin® (conjugated estrogens) 0.3 mg PO QD; may titrate if 0.3 to 1.25 mg PO QD Varies by formulation Premphase®, Prempro® (conjugated estrogens/ medroxyprogesterone) needed 1 tablet PO QD
      Page 3 of 7 Varies 1.25 mg/day 1.25 mg/day 1 tablet/day

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   Conjugated Estrogens/Bazedoxifene Drug Name Dosing Regimen Oral Bisphosphonates alendronate (Fosamax®) ibandronate (Boniva®) risedronate (Actonel®) 5 mg PO QD or 35 mg PO q week 150 mg PO q month 5 mg PO QD or
   35 mg PO q week or
   75 mg PO QD for 2 consecutive days for 2 doses/month or
   150 mg PO q month
   Dose Limit/ Maximum Dose 5 mg/day or 35 mg/week 150 mg/month 5 mg/day or
   35 mg/week or
   150 mg/month Selective Estrogen Receptor Modulators (SERMs) raloxifene (Evista®) 60 mg PO QD Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. 60 mg/day Appendix C: Contraindications/Boxed Warnings • Contraindication(s): undiagnosed abnormal uterine bleeding; known suspected or past history of breast cancer; known or suspected estrogen-dependent neoplasia; active or past history of venous thromboembolism; active or past history of arterial thromboembolism; hypersensitivity (angioedema, anaphylaxis) to estrogens, bazedoxifene, or any ingredients; known hepatic impairment or disease; known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders; pregnancy, women who may become pregnant, and nursing mothers • Boxed warning(s): endometrial cancer, cardiovascular disorders, and probable dementia Appendix D: General Information • Duavee is not recommended for use in women greater than 75 years of age. An increased risk of probable dementia in women over 65 years of age was reported in the Women's Health Initiative (WHI) Memory ancillary studies of the WHI using daily conjugated estrogens (0.625 mg).
   • Women taking Duavee should not take additional estrogens. • There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Duavee has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer.
   • Estrogen therapy should not be used for the prevention of cardiovascular disease or dementia. • The WHI estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (0.625 mg)-alone, relative to placebo. V. Dosage and Administration
   Indication Vasomotor symptoms, osteoporosis Dosing Regimen 1 tablet PO QD Maximum Dose 1 tablet/day Page 4 of 7

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   Conjugated Estrogens/Bazedoxifene VI. Product Availability
   Tablet: 0.45 mg/20 mg VII.