Duavee
conjugated estrogens/bazedoxifene · Tablet, Film Coated · Oral
• Women taking DUAVEE should not take additional estrogens [see Warnings and Precautions (5.1) ]
• 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 [see Warnings and Precautions (5.3) ]
• Estrogen therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions (5.2 , 5.4) ]
• The Women's Health Initiative (WHI) estrogen-alone substudy reported increased risks of…
Uses
1 INDICATIONS AND USAGE DUAVEE is indicated in women with a uterus for: DUAVEE is a combination of conjugated estrogens with an estrogen agonist/antagonist indicated for treatment of the following conditions in women with a uterus:
• Treatment of moderate to severe vasomotor symptoms associated with menopause ( 1.1 )
• Prevention of postmenopausal osteoporosis ( 1.2 ) Limitation of Use : DUAVEE should be used for the shortest duration consistent with treatment goals and risks for the individual woman ( 1.3 ) 1.1 Treatment of Moderate to Severe Vasomotor Symptoms Associated with Menopause 1.2 Prevention of Postmenopausal Osteoporosis 1.3 Important Limitations of Use
• Use DUAVEE 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.
Dosage and administration
• Take one tablet orally once daily ( 2 ) 2.1 Treatment of Moderate to Severe Vasomotor Symptoms Associated with Menopause The recommended dosage is one DUAVEE tablet daily. 2.2 Prevention of Postmenopausal Osteoporosis The recommended dosage is one DUAVEE tablet daily. 2.3 General Dosing Information Take DUAVEE once daily, without regard to meals. Tablets should be swallowed whole. 2.4 Recommendations for Calcium and Vitamin D Supplementation Women taking DUAVEE for prevention of postmenopausal osteoporosis should add supplemental calcium and/or vitamin D to their diet if daily intake is inadequate. 2.5 Administration Instructions for Missed Doses If a dose of DUAVEE is missed, instruct patients to take it as soon as remembered unless it is almost time for the next scheduled dose. They should not take two doses at the same time. 2.6 Use in Patients with Renal Impairment The pharmacokinetics of DUAVEE have not been evaluated in patients with renal impairment. Use in patients with renal impairment is not recommended [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . 2.7 Use in the Elderly DUAVEE has not been studied in women over 75 years of age. Use in women over 75 years of age is not recommended.
Dosage forms and strengths
(conjugated estrogens/bazedoxifene) tablets, 0.45 mg/20 mg are oval, biconvex, pink tablets, branded with "0.45/20" in black ink on one side. Tablet containing conjugated estrogens 0.45 mg and bazedoxifene 20 mg ( 3 )
Contraindications
4 CONTRAINDICATIONS DUAVEE is contraindicated in women with any of the following conditions:
• 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 (for example, anaphylaxis, angioedema) 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, as DUAVEE may cause fetal harm [see pregnancy (8.1) ] .
• Undiagnosed abnormal uterine bleeding ( 4 , 5.3 )
• Known, suspected, or past history of breast cancer ( 4 , 5.3 )
• Known or suspected estrogen-dependent neoplasia ( 4 , 5.3 )
• Active or past history of venous thromboembolism ( 4 , 5.2 )
• Active or past history of arterial thromboembolism ( 4 , 5.2 )
• Hypersensitivity (angioedema, anaphylaxis) to estrogens, bazedoxifene, or any ingredients ( 4 )
• Known hepatic impairment or disease ( 4 , 5.9 , 8.7, 12.3 )
• Known protein C, protein S, or antithrombin deficiency or other known thrombophilic disorders ( 4 )
• Pregnancy ( 1 , 4 , 8.1 )
Warnings and precautions
• Women taking DUAVEE should not take progestins, additional estrogens or additional estrogen agonist/antagonists ( 5.1 )
• Cardiovascular disorders, including venous thromboembolism, pulmonary embolism, stroke, and retinal vascular thrombosis ( 5.2 , 5.6 )
• Malignant neoplasms, including endometrial cancer, breast cancer, and ovarian cancer ( 5.3 )
• Estrogens increase the risk of gallbladder disease ( 5.5 )
• Discontinue estrogen if loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs ( 5.6 , 5.8 , 5.9 )
• Monitor thyroid function in women on thyroid replacement therapy ( 5.10 , 5.17 ) 5.1 Drugs Containing Progestins, Estrogens or Estrogen Agonist/Antagonists DUAVEE contains conjugated estrogens and bazedoxifene, an estrogen agonist/antagonist. Women taking DUAVEE should not take progestins, additional estrogens or additional estrogen agonist/antagonists. 5.2 Cardiovascular Disorders 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. 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. Stroke In the WHI estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily conjugated estrogens (CE) (0.625 mg)-alone compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years). The increase in risk was demonstrated in year 1 and persisted [see Clinical Studies (14.5) ] . Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving conjugated estrogens (0.625 mg)-alone versus those receiving placebo (18 versus 21 per 10,000 women-years). Should a stroke occur or be suspected, DUAVEE should be discontinued immediately [see Contraindications (4) ]. Coronary Heart Disease In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (defined as nonfatal myocardial infarction, silent myocardial infarction, or CHD death) was reported in women receiving estrogen-alone compared to placebo [see Clinical Studies (14.5) ] . Subgroup analyses of women 50 to 59 years of age suggest a statistically non-significant reduction in CHD events (CE [0.625 mg]-alone compared to placebo) in women with less than 10 years since menopause (8 versus 16 per 10,000 women-years). Venous Thromboembolism (VTE) In the WHI estrogen-alone substudy, the risk of VTE [DVT and pulmonary embolism (PE)] was increased for women receiving daily conjugated estrogens (0.625 mg)-alone compared to placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women-years). The increase in VTE risk was demonstrated during the first 2 years [see Clinical Studies (14.5) ] . If feasible, DUAVEE should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. Because immobilization increases the risk for venous thromboembolic events independent of therapy, DUAVEE should be discontinued prior to and during prolonged immobilization (e.g., post-surgical recovery, prolonged bed rest) and DUAVEE therapy should be resumed only after the patient is fully ambulatory. In addition, women taking DUAVEE should be advised to move about periodically during travel involving prolonged immobilization. 5.3 Malignant Neoplasms Endometrial Cancer An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in women with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2 to 12 times greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than 1 year. The greatest risk appears associated with prolonged use, with increased risks of 15- to 24-fold for 5 to 10 years or more of treatment. This risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. DUAVEE contains an estrogen agonist/antagonist. This component reduces the risk of endometrial hyperplasia that can occur with the conjugated estrogens component. Endometrial hyperplasia may be a precursor to endometrial cancer. Women taking DUAVEE should not take additional estrogens as this may increase the risk of endometrial hyperplasia. Clinical surveillance of all women taking DUAVEE is important. 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. Breast Cancer The WHI substudy of daily conjugated estrogens (0.625 mg)-alone provided information about breast cancer in estrogen‑alone users. In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily conjugated estrogen (0.625 mg)-alone was not associated with an increased risk of invasive breast cancer (relative risk [RR] 0.80). 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. All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations.
Side effects
The following adverse reactions are discussed in greater detail in other sections of the label:
• Cardiovascular Disorders [see Warnings and Precautions (5.2) ]
• Malignant Neoplasms [see Warnings and Precautions (5.3) ]
• Gallbladder Disease [see Warnings and Precautions (5.5) ]
• Hypertriglyceridemia [see Warnings and Precautions (5.8) ] In four prospective, randomized, placebo-controlled trials the common adverse reactions (incidence ≥ 5%) were muscle spasms, nausea, diarrhea, dyspepsia, abdominal pain upper, oropharyngeal pain, dizziness, and neck pain ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of conjugated estrogens/bazedoxifene was evaluated in four Phase 3 clinical trials ranging from 12 weeks to 24 months in duration and enrolling 6,210 postmenopausal women age 40 to 75 years (mean age 55 years). A total of 1,224 patients were treated with DUAVEE and 1,069 patients received placebo. Women enrolled in Studies 1 and 2 received calcium (600–1200 mg) and vitamin D (200–400 IU) daily, while women in Studies 3 and 4 received no calcium and vitamin D supplementation as part of the protocol. The incidence of all-cause mortality was 0.0% in the DUAVEE group and 0.2% in the placebo group. The incidence of serious adverse reactions was 3.5% in the DUAVEE group and 4.8% in the placebo group. The percentage of patients who withdrew from treatment due to adverse reactions was 7.5% in the DUAVEE group and 10.0% in the placebo group. The most common adverse reactions leading to discontinuation were hot flush, abdominal pain upper, and nausea. The most commonly observed adverse reactions (incidence ≥ 5%) more frequently reported in women treated with DUAVEE than placebo are presented in Table 1. Table 1: Adverse Reactions (Incidence ≥ 5%) More Common in the DUAVEE Treatment Group in Placebo-controlled Trials DUAVEE (N=1224) n (%) Placebo (N=1069) n (%) Gastrointestinal disorders Nausea 100 (8) 58 (5) Diarrhea 96 (8) 57 (5) Dyspepsia 84 (7) 59 (6) Abdominal pain upper 81 (7) 58 (5) Musculoskeletal and connective tissue disorders Muscle spasms 110 (9) 63 (6) Neck pain 62 (5) 46 (4) Nervous system disorders Dizziness 65 (5) 37 (3) Respiratory, thoracic, and mediastinal disorders Oropharyngeal pain 80 (7) 61 (6) Venous thromboembolism : In the clinical studies with DUAVEE, the reporting rates for venous thromboembolism (deep venous thrombosis, pulmonary embolism, and retinal vein thrombosis) were low in all treatment groups. Adverse reactions of venous thromboembolism were reported in 0.0% of patients treated with DUAVEE and 0.1% of patients treated with placebo. Due to the low rate of events in both groups, it is not possible to conclude that the risk of venous thromboembolism with DUAVEE is different from that seen with other estrogen therapies [see Warnings and Precautions (5.2) ] .
Drug interactions
7.1 Cytochrome P450 (CYP) In vitro and in vivo studies have shown that estrogens are metabolized partially by cytochrome P450 3A4 (CYP3A4). 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 [see Pharmacokinetics (12.3) ] . 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. Bazedoxifene does not induce or inhibit the activities of major CYP isoenzymes. In vitro data suggest that bazedoxifene is unlikely to interact with co-administered drugs via CYP-mediated metabolism. 7.2 Uridine Diphosphate Glucuronosyltransferase (UGT) Bazedoxifene undergoes metabolism by UGT enzymes in the intestinal tract and liver. 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. 7.3 Atorvastatin Concomitant administration of bazedoxifene (40 mg daily) and atorvastatin (20 mg, single-dose) to healthy postmenopausal women did not affect the pharmacokinetics of bazedoxifene, atorvastatin or its active metabolites.
Use in specific populations
• Geriatric Use: DUAVEE was not studied in women aged 75 or older ( 8.5 , 12.3 ); use in this population is not recommended ( 2.7 , 8.5 )
• An increased risk of probable dementia in women over 65 years of age was reported in the Women's Health Initiative Memory ancillary studies of the Women's Health Initiative ( 5.4 , 8.5 , 14.6 )
• Renal Impairment: DUAVEE was not studied in women with renal impairment; use in this population is not recommended ( 2.6 , 8.6 , 12.3 ) 8.1 Pregnancy Risk Summary DUAVEE is contraindicated for use in pregnant women and is not indicated for use in females of reproductive potential [see Contraindications (4) , Warnings and Precautions (5.15) ]. Conjugated Estrogens (CE) There are no data with the use of conjugated estrogens in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital and non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives before conception or during early pregnancy. Bazedoxifene There are no available data on bazedoxifene use in pregnant women to inform a drug associated risk of adverse developmental outcomes. Animal studies have shown that oral bazedoxifene administered during the period of organogenesis to pregnant rats or rabbits at 0.3 and 2 times, respectively, the exposure at the maximum recommended dose, can cause fetal harm [see Data ]. Based on mechanism of action, bazedoxifene may block the important functions that estrogen has during all stages of pregnancy [see Clinical Pharmacology (12.1) ] . Data Animal data Bazedoxifene Administration of bazedoxifene to rats at maternally toxic dosages ≥1 mg/kg/day (≥ 0.3 times the human area under the curve (AUC) at the 20 mg dose) resulted in reduced numbers of live fetuses and/or reductions in fetal body weights. No fetal developmental anomalies were observed. In studies conducted with pregnant rabbits treated with bazedoxifene, abortion and an increased incidence of heart (ventricular septal defect) and skeletal system (ossification delays, misshapen or misaligned bones, primarily of the spine and skull) anomalies in the fetuses were present at maternally toxic dosages of ≥ 0.5 mg/kg/day (≥ 2 times the human AUC at the 20 mg dose). 8.2 Lactation Risk Summary DUAVEE is not indicated for use in females of reproductive potential [see Warnings and Precautions (5.15) ] . Conjugated Estrogens Estrogens are present in human milk and can reduce milk production in breast-feeding females. This reduction can occur at any time but is less likely to occur once breast-feeding is well-established. Bazedoxifene There are no data on the presence of bazedoxifene in either human or animal breast milk, the effect on the breastfed infant, or the effects on milk production. Based on mechanism of action, bazedoxifene may block the important functions that estrogen has in mammary tissue during lactation [see Clinical Pharmacology (12.1) ]. 8.3 Females and Males of Reproductive Potential Infertility Bazedoxifene Based on animal data, bazedoxifene administration may adversely affect female fertility. However, clinical fertility studies with bazedoxifene have not been conducted [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use DUAVEE is not indicated for use in children [see Indications and Usage (1) ] . 8.5 Geriatric Use DUAVEE is not recommended for use in women greater than 75 years of age [see Dosage and Administration (2.7) and Clinical Pharmacology 12.3) ] . Of the total number of women in phase 3 clinical studies who received DUAVEE, 4.60% (n=224) were 65 years and over. DUAVEE was not studied in women aged 75 and over. No overall differences in safety or effectiveness were observed between women 65–74 years of age and younger women, and other reported clinical experience has not identified differences in responses between the elderly and younger women, but greater sensitivity of some older women cannot be ruled out. An increased risk of probable dementia in women over 65 years of age was reported in the Women's Health Initiative Memory ancillary studies of the Women's Health Initiative using daily conjugated estrogens (0.625 mg) [see Clinical Studies (14.6) ]. 8.6 Renal Impairment DUAVEE is not recommended for use in patients with renal impairment [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3)] . The pharmacokinetics, safety, and efficacy of DUAVEE have not been evaluated in women with renal impairment . 8.7 Hepatic Impairment DUAVEE is contraindicated in patients with hepatic impairment [see Contraindications (4) and Clinical Pharmacology (12.3)] . The pharmacokinetics, safety, and efficacy of DUAVEE have not been evaluated in women with hepatic impairment. In a pharmacokinetics study of bazedoxifene 20 mg alone, the C max and AUC of bazedoxifene increased 67% and 143%, respectively, in women with mild hepatic impairment (Child Pugh Class A), compared to healthy women. The C max and AUC of bazedoxifene increased 32% and 109%, respectively, in women with moderate hepatic impairment (Child Pugh Class B). The C max and AUC of bazedoxifene increased 20% and 268%, respectively, in women with severe hepatic impairment (Child Pugh Class C). No pharmacokinetic studies with conjugated estrogens were conducted in women with hepatic impairment. 8.8 Body Mass Index (BMI) Following DUAVEE administration, the systemic exposures of conjugated estrogens and bazedoxifene were lower in obese subjects, compared to non-obese subjects [see Pharmacokinetics (12.3) ] . A single dose of DUAVEE (conjugated estrogens 0.45 mg/bazedoxifene 20 mg) was administered to 12 obese BMI ≥ 30 [mean (SD) = 32.7 (2.7) kg/m 2 ] and 12 non-obese BMI < 30 [mean (SD) 25.3 (2.6) kg/m 2 ] postmenopausal women. In obese subjects, systemic exposures of total estrone, total equilin, and bazedoxifene were 2%, 32%, and 13% lower, respectively, compared to non-obese subjects.
Pregnancy
8.1 Pregnancy Risk Summary DUAVEE is contraindicated for use in pregnant women and is not indicated for use in females of reproductive potential [see Contraindications (4) , Warnings and Precautions (5.15) ]. Conjugated Estrogens (CE) There are no data with the use of conjugated estrogens in pregnant women; however, epidemiologic studies and meta-analyses have not found an increased risk of genital and non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to combined hormonal contraceptives before conception or during early pregnancy. Bazedoxifene There are no available data on bazedoxifene use in pregnant women to inform a drug associated risk of adverse developmental outcomes. Animal studies have shown that oral bazedoxifene administered during the period of organogenesis to pregnant rats or rabbits at 0.3 and 2 times, respectively, the exposure at the maximum recommended dose, can cause fetal harm [see Data ]. Based on mechanism of action, bazedoxifene may block the important functions that estrogen has during all stages of pregnancy [see Clinical Pharmacology (12.1) ] . Data Animal data Bazedoxifene Administration of bazedoxifene to rats at maternally toxic dosages ≥1 mg/kg/day (≥ 0.3 times the human area under the curve (AUC) at the 20 mg dose) resulted in reduced numbers of live fetuses and/or reductions in fetal body weights. No fetal developmental anomalies were observed. In studies conducted with pregnant rabbits treated with bazedoxifene, abortion and an increased incidence of heart (ventricular septal defect) and skeletal system (ossification delays, misshapen or misaligned bones, primarily of the spine and skull) anomalies in the fetuses were present at maternally toxic dosages of ≥ 0.5 mg/kg/day (≥ 2 times the human AUC at the 20 mg dose).
Pediatric use
8.4 Pediatric Use DUAVEE is not indicated for use in children [see Indications and Usage (1) ] .
Geriatric use
8.5 Geriatric Use DUAVEE is not recommended for use in women greater than 75 years of age [see Dosage and Administration (2.7) and Clinical Pharmacology 12.3) ] . Of the total number of women in phase 3 clinical studies who received DUAVEE, 4.60% (n=224) were 65 years and over. DUAVEE was not studied in women aged 75 and over. No overall differences in safety or effectiveness were observed between women 65–74 years of age and younger women, and other reported clinical experience has not identified differences in responses between the elderly and younger women, but greater sensitivity of some older women cannot be ruled out. An increased risk of probable dementia in women over 65 years of age was reported in the Women's Health Initiative Memory ancillary studies of the Women's Health Initiative using daily conjugated estrogens (0.625 mg) [see Clinical Studies (14.6) ].
Overdosage
In case of overdosage, there is no specific antidote, and the treatment should be symptomatic. Symptoms of overdosage of estrogen-containing products in adults and children may include nausea, vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue; withdrawal bleeding may occur.
Description
(conjugated estrogens/bazedoxifene), contains conjugated estrogens with bazedoxifene, an estrogen agonist/antagonist. Conjugated estrogens are purified from pregnant mares' urine and consist of the sodium salts of water-soluble estrogen sulfates blended to represent the average composition of material derived from pregnant mares' urine. Conjugated estrogens are a mixture of sodium estrone sulfate and sodium equilin sulfate, and also contain as concomitant components, sodium sulfate conjugates, 17α-dihydroequilin, 17α-estradiol, and 17β-dihydroequilin. Bazedoxifene is supplied as the acetate salt (bazedoxifene acetate) and has the chemical name 1 H -Indol-5-ol, 1-[[4-[2-(hexahydro-1 H -azepin-1-yl) ethoxy]phenyl]methyl]-2-(4-hydroxyphenyl)-3-methyl-, monoacetate. The empirical formula is C 30 H 34 N 2 O 3 ∙ C 2 H 4 O 2, and the molecular weight is 530.65. Bazedoxifene acetate is a white to tan powder. The aqueous solubility of bazedoxifene is pH-dependent. Solubility is higher at lower pH. The solubility of bazedoxifene acetate in unbuffered sterile water was measured to be 923 microgramsA/mL at pH 5.4. The following represents the chemical structure of bazedoxifene acetate: DUAVEE is available for oral administration as tablets containing 0.45 mg of conjugated estrogens with 20 mg of bazedoxifene (equivalent to 22.6 mg of bazedoxifene acetate). Each tablet of DUAVEE contains the following inactive ingredients: calcium phosphate tribasic, hydroxypropyl cellulose, microcrystalline cellulose, powdered cellulose, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, sucrose, ascorbic acid, sucrose palmitic acid ester, hydroxyethylcellulose, titanium dioxide, red iron oxide, yellow iron oxide, black iron oxide, povidone, polydextrose, maltitol, poloxamer 188, propylene glycol, and isopropyl alcohol. Chemical Structure
Mechanism of action
12.1 Mechanism of Action DUAVEE pairs conjugated estrogens with bazedoxifene. Conjugated estrogens and bazedoxifene function by binding to and activating estrogen receptors (ER) α and β, which vary in proportion from tissue to tissue. Conjugated estrogens are composed of multiple estrogens and are agonists of ER- α and β. Bazedoxifene is an estrogen agonist/antagonist that acts as an agonist in some estrogen-sensitive tissues and an antagonist in others (e.g., uterus). 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.
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING DUAVEE tablets contain 0.45 mg conjugated estrogens and 20 mg bazedoxifene. The tablets are oval, biconvex, and pink, branded with "0.45/20" in black ink on one side. DUAVEE ® tablets are supplied as follows: Package NDC number Conjugated estrogens 0.45 mg/bazedoxifene 20 mg 2 blisters of 15 tablets each NDC 0008-1123-12 Storage Blisters DUAVEE tablets should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). See USP Controlled Room Temperature. Dispense product in the original package. Tablets should not be removed from blisters until immediately before use. Protect from moisture. After opening foil pouch, product must be used within 60 days.
Storage
Storage Blisters DUAVEE tablets should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). See USP Controlled Room Temperature. Dispense product in the original package. Tablets should not be removed from blisters until immediately before use. Protect from moisture. After opening foil pouch, product must be used within 60 days.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information) . 17.1 Instructions for Patients
• Keep DUAVEE in the original container to protect from moisture. Do not place DUAVEE in pill boxes or pill organizers.
• If more than one blister package is dispensed to the patient, instruct them to open one foil pouch at a time.
• Instruct patient to record the date the blister package is opened in the space provided on the blister package label. Do not use if the blister package has been open more than 60 days.
• Instruct patient to remove only one tablet from the blister package at the time of use. 17.2 Venous Thromboembolic Events Advise patients to immediately report to their physician any signs or symptoms related to venous thrombosis and thromboembolic events [see Warnings and Precautions (5.2) ] . 17.3 Abnormal Vaginal Bleeding Inform postmenopausal women of the importance of reporting abnormal vaginal bleeding to their healthcare provider as soon as possible [see Warnings and Precautions (5.3) ]. 17.4 Possible Serious Adverse Reactions with Estrogen Therapy Inform postmenopausal women of possible serious adverse reactions of estrogen therapy including Cardiovascular Disorders, Malignant Neoplasms, and Probable Dementia [see Warnings and Precautions (5.2 , 5.3 , 5.4) ] . 17.5 Possible Less Serious Adverse Reactions with DUAVEE Inform postmenopausal women of possible less serious but common adverse reactions of DUAVEE therapy such as muscle spasms, nausea, diarrhea, dyspepsia, upper abdominal pain, throat pain, dizziness and neck pain. 17.6 Calcium and Vitamin D Intake Advise patients to add supplemental calcium and/or vitamin D to the diet if daily intake is inadequate.
Label text from the FDA structured product label by U.S. Pharmaceuticals (revised Jul 31, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Estrogens, Conjugated in 2 products
- Bazedoxifene Acetate in 2 products
Duavee NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 63539-122 | Estrogens, Conjugated .45 mg/1; Bazedoxifene Acetate 20 mg/1 Tablet, Film Coated | U.S. Pharmaceuticals | NDA |
| 0008-1123 | Estrogens, Conjugated .45 mg/1; Bazedoxifene Acetate 20 mg/1 Tablet, Film Coated | Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc. | NDA |
Frequently asked questions
What is Duavee used for?
1 INDICATIONS AND USAGE DUAVEE is indicated in women with a uterus for: DUAVEE is a combination of conjugated estrogens with an estrogen agonist/antagonist indicated for treatment of the following conditions in women with a uterus: • Treatment of moderate to severe vasomotor symptoms associated with menopause ( 1.1 ) • Prevention of postmenopausal osteoporosis ( 1.2 ) Limitation of Use : DUAVEE…
What are the side effects of Duavee?
The following adverse reactions are discussed in greater detail in other sections of the label: • Cardiovascular Disorders [see Warnings and Precautions (5.2) ] • Malignant Neoplasms [see Warnings and Precautions (5.3) ] • Gallbladder Disease [see Warnings and Precautions (5.5) ] • Hypertriglyceridemia [see Warnings and Precautions (5.8) ] In four prospective, randomized, placebo-controlled… See the full label for the complete list.
Who makes Duavee?
Duavee is listed by 2 labelers in the FDA NDC directory, including U.S. Pharmaceuticals, Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc..