Indicated in women with a uterus for:

• Treatment of Moderate to Severe Vasomotor Symptoms Associated with Menopause 

• Prevention of Postmenopausal Osteoporosis

DUAVEE should be used for the shortest duration consistent with treatment goals and risks for the individual woman. 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.

DUAVEE has not been studied in women over 75 years of age. Use in women over 75 years of age is not recommended.

DUAVEE contains conjugated estrogens and bazedoxifene, an estrogen agonist/antagonist. Women taking DUAVEE should not take progestins, additional estrogens or additional estrogen agonist/antagonists.

Estrogen therapy should not be used for the prevention of cardiovascular disease or dementia.

There is no indication for premenopausal use of DUAVEE. The efficacy and safety of DUAVEE in premenopausal women have not been established, and its use is not recommended.

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. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

The use of estrogen-alone has been reported to result in an increase in abnormal mammograms requiring further evaluation. The effect of treatment with DUAVEE on the risk of breast cancer is unknown.

The effect of treatment with DUAVEE on the risk of ovarian cancer is unknown.

The Women’s Health Initiative (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.

Retinal vascular thrombosis has been reported in patients receiving estrogens.

Estrogen agonist/antagonists (including bazedoxifene, a component of DUAVEE) and estrogens individually are known to increase the risk of VTE.

An increased risk of stroke and DVT has been reported with estrogen-alone therapy. Should any of these occur or be suspected, DUAVEE should be discontinued immediately.

Increased risk of probable dementia in postmenopausal women 65 years of age and older during 5.2 years of treatment with daily conjugated estrogens (0.625 mg) alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.In the absence of comparable data, these risks should be assumed to be similar for other doses of conjugated estrogens and other dosage forms of estrogens.

The pharmacokinetics of DUAVEE have not been evaluated in patients with renal impairment. Use in patients with renal impairment is not recommended.

A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.

In women with pre-existing hypertriglyceridemia, treatment with estrogens may be associated with elevations of plasma triglycerides leading to pancreatitis. In a small number of case reports in women receiving estrogens, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens.

Estrogens may cause some degree of fluid retention. Because of this, patients who have conditions that might be influenced by this factor, such as cardiac dysfunction or renal impairment, warrant careful observation when estrogens are prescribed.

Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur.

Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or VTE (for example, personal history or family history of VTE, obesity, and systemic lupus erythematosus) should be managed appropriately.

Estrogens may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine or porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions.

DUAVEE has not been studied in women with impaired liver function or past history of cholestatic jaundice. Estrogens may be poorly metabolized in women with impaired liver function.

Exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema.

DUAVEE is contraindicated in patients with:

• Undiagnosed abnormal uterine bleeding
• Known, suspected, or past history of breast cancer 
• Known or suspected estrogen-dependent neoplasia
• Active deep venous thrombosis, pulmonary embolism, or history of these conditions
• Active arterial thromboembolic disease (for example, stroke, myocardial infarction) or history of these conditions
• 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

Estrogen administration leads to increased thyroid-binding globulin (TBG) levels. Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range. Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range.

Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity.

Concomitant administration of itraconazole, a strong CYP3A4 inhibitor, with DUAVEE, resulted in increases in bazedoxifene exposure (40%) and, to a lesser extent, conjugated estrogens exposure (9% for baseline-adjusted total estrone, 5% for total equilin), compared to DUAVEE alone. Inducers of CYP3A4, such as St. John’s Wort (Hypericum perforatum) preparations, phenobarbital, carbamazepine, and rifampin, may reduce plasma concentrations of some estrogens, possibly resulting in a decrease in therapeutic effects and/or changes in the uterine bleeding profile.

The metabolism of bazedoxifene may be increased by concomitant use of substances known to induce UGTs, such as rifampin, phenobarbital, carbamazepine, and phenytoin. A reduction in bazedoxifene exposure may be associated with an increase risk of endometrial hyperplasia. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Co-administration of ibuprofen and bazedoxifene increased Cmax and AUC of bazedoxifene by 18% and 7%, respectively.

Co-administration of atorvastatin and bazedoxifene decreased Cmax of bazedoxifene by 3% and increased AUC of bazedoxifene by 6%.

Co-administration of azithromycin and bazedoxifene increased Cmax of bazedoxifene by 6% and decreased AUC of bazedoxifene by 15%.

Co-administration of aluminum/magnesium hydroxide and bazedoxifene decreased Cmax of bazedoxifene by 8% and increased AUC of bazedoxifene by 7%.

DUAVEE must not be used in women who are or may become pregnant.

DUAVEE should not be used by lactating women.

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Use in premenopausal patients. GoToSource 

Use in postmenopausal women without a uterus. GoToSource

Increased risk of stroke, deep vein thrombosis and retinal vascular thrombosis. GoToSource

Endometrial hyperplasia (thickening of the lining of uterus) malignant neoplasms, including endometrial cancer, breast cancer and ovarian cancer, increased risk of gallbladder disease, hypocalcemia (low calcium level in blood), elevated blood pressure, exacerbation of asthma, diabetes mellitus, epilepsy, migraine, or porphyria, systemic lupus erythematosus, hepatic hemangioma (noncancerous tumor in the liver) and increased risk of dementia in women older than 65 years. GoToSource

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