Clinical Policy: Conjugated Estrogens/Bazedoxifene (Duavee) Form

Page 1 of 7 Clinical Policy: Conjugated Estrogens/Bazedoxifene (Duavee) Reference Number: CP.PMN.258
Effective Date: 03.01.21
Last Review Date: 02.26
Line of Business: HIM, Medicaid Revision Log

See Important Reminder at the end of this policy for important regulatory and legal information.

Description
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.

CLINICAL POLICY

Conjugated Estrogens/Bazedoxifene

Page 3 of 7

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

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

4. 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

5. 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®) Varies by formulation Varies Menest® (esterified estrogens) 0.3 to 1.25 mg PO QD 1.25 mg/day

CLINICAL POLICY

Conjugated Estrogens/Bazedoxifene

Page 4 of 7 Drug Name

Dosing Regimen Dose Limit/ Maximum Dose Premarin® (conjugated estrogens) 0.3 mg PO QD; may titrate if needed 1.25 mg/day Premphase®, Prempro® (conjugated estrogens/ medroxyprogesterone) 1 tablet PO QD
1 tablet/day Oral Bisphosphonates alendronate (Fosamax®) 5 mg PO QD or 35 mg PO q week 5 mg/day or 35 mg/week ibandronate (Boniva®) 150 mg PO q month 150 mg/month risedronate (Actonel®) 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
5 mg/day or
35 mg/week or
150 mg/month Selective Estrogen Receptor Modulators (SERMs) raloxifene (Evista®) 60 mg PO QD 60 mg/day 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.

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.

CLINICAL POLICY

Conjugated Estrogens/Bazedoxifene

Page 5 of 7 V. Dosage and Administration
Indication Dosing Regimen Maximum Dose Vasomotor symptoms, osteoporosis 1 tablet PO QD 1 tablet/day

VI. Product Availability
Tablet: 0.45 mg/20 mg

Reviews, Revisions, and Approvals Date P&T Approval Date 1Q 2022 annual review: no significant changes; references reviewed and updated. 09.13.21 02.22 Template changes applied to other diagnoses/indications and continued therapy section. 10.06.22

1Q 2023 annual review: no significant changes; references reviewed and updated.
11.02.22 02.23 1Q 2024 annual review: no significant changes; for osteoporosis initial criteria, added "generic" before alendronate to clarify that generic is preferred; for Appendix B, removed estropiate due to product unavailability and updated and updated dosing regimen; references reviewed and updated.
10.20.23 02.24 1Q 2025 annual review: no significant changes; references reviewed and updated. 10.22.24 02.25 Added step therapy bypass for IL HIM per IL HB 5395. 09.16.25

CLINICAL POLICY

Conjugated Estrogens/Bazedoxifene

Page 6 of 7 Reviews, Revisions, and Approvals Date P&T Approval Date 1Q 2026 annual review: no significant changes; revised initial approval duration from 6 to 12 months; references reviewed and updated. 10.13.25 02.26

The date of posting may not be the effective date of this clinical policy.