DUAVEE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DUAVEE (DUAVEE).
DUAVEE is a combination of conjugated estrogens (CE) and bazedoxifene (BZA). CE activates estrogen receptors (ERα and ERβ) to relieve menopausal symptoms; BZA is a selective estrogen receptor modulator (SERM) that antagonizes ER in the endometrium to prevent endometrial hyperplasia.
| Metabolism | Conjugated estrogens are primarily metabolized in the liver via phase II conjugation (sulfation and glucuronidation) by enzymes such as UGT1A1, UGT1A8, UGT1A9, UGT2B7, and SULT1A1. Bazedoxifene undergoes hepatic metabolism via glucuronidation by UGT1A1, UGT1A8, UGT1A9, and UGT2B7, with minimal CYP involvement. |
| Excretion | Conjugated estrogens are primarily excreted in urine as glucuronide and sulfate conjugates, with approximately 10-15% excreted in feces via biliary elimination. Bazedoxifene is mainly eliminated in feces (85%) with minimal renal excretion (<1% as unchanged drug). |
| Half-life | Conjugated estrogens: terminal half-life of estrone sulfate is approximately 10-24 hours. Bazedoxifene: terminal half-life is approximately 30 hours. Clinically, steady state is achieved within 7 days for estrogens and 10-14 days for bazedoxifene. |
| Protein binding | Conjugated estrogens: extensive binding to albumin (approximately 80-85%). Bazedoxifene: highly bound (>99%) to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Conjugated estrogens: Vd approximately 0.5-2 L/kg, indicating distribution into total body water and tissues. Bazedoxifene: Vd approximately 1.2 L/kg, suggesting extensive tissue distribution. |
| Bioavailability | Conjugated estrogens: oral bioavailability is approximately 30-50% due to first-pass metabolism. Bazedoxifene: absolute oral bioavailability is approximately 6% due to extensive first-pass glucuronidation. |
| Onset of Action | Oral administration: onset of action for estrogenic effects (e.g., relief of vasomotor symptoms) occurs within 2-4 weeks. Bazedoxifene's effect on bone turnover markers is detectable within 4 weeks. |
| Duration of Action | After oral administration, estrogenic effects last 24 hours with once-daily dosing. Bazedoxifene provides sustained serum levels over 24 hours; tissue effects persist with continued dosing. |
| Molecular Weight | 530.73 |
One tablet (conjugated estrogens 0.45 mg/bazedoxifene 20 mg) orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | Contraindicated in Child-Pugh Class C (severe hepatic impairment). Use with caution in Child-Pugh Class A or B; no specific dose adjustment established, but monitor closely. |
| Pediatric use | Not indicated for use in pediatric patients. Safety and efficacy have not been established. |
| Geriatric use | No specific dose adjustment recommended. Higher risk of adverse events (e.g., thromboembolism, stroke) in women >65 years of age; use lowest effective dose for shortest duration. |
| 1st trimester | Contraindicated in pregnancy. Conjugated estrogens/bazedoxifene should not be used during pregnancy. There is no indication for use in pregnant women. |
| 2nd trimester | Contraindicated in pregnancy. Estrogens may cause fetal harm, and bazedoxifene may affect fetal development. |
| 3rd trimester | Contraindicated in pregnancy. Avoid use due to potential adverse effects on the fetus. |
Clinical note
Comprehensive clinical and safety monograph for DUAVEE (DUAVEE).
| Placental transfer | Estrogens cross the placenta. Bazedoxifene is likely to cross based on molecular weight and animal studies. |
| Breastfeeding | Estrogens are excreted in human milk and may reduce milk production. Bazedoxifene is not known to be excreted in human milk but may have effects on the infant. Use is not recommended during breastfeeding. |
■ FDA Black Box Warning
Estrogen therapy increases the risk of endometrial cancer in women with a uterus. Concomitant use of a progestin or bazedoxifene is required to reduce this risk. Cardiovascular disorders: Estrogen-alone therapy may increase risk of stroke and DVT. Estrogen plus progestin therapy increases risk of MI, stroke, invasive breast cancer, pulmonary emboli, and DVT. DUAVEE is not approved for cardiovascular disease prevention. Breast cancer: Estrogen plus progestin therapy increases risk of invasive breast cancer. Probable dementia: Estrogen plus progestin therapy increases risk in women 65+.
| Serious Effects |
PregnancyUndiagnosed abnormal genital bleedingKnown or suspected breast cancerKnown or suspected estrogen-dependent neoplasiaActive or past history of venous thromboembolismActive or past history of arterial thromboembolismHypersensitivity to conjugated estrogens or bazedoxifene
| Precautions | Cardiovascular disorders (stroke, DVT, MI, pulmonary embolism), Malignant neoplasms (endometrial cancer, breast cancer), Gallbladder disease, Hypertriglyceridemia, Fluid retention, Hypocalcemia, Hereditary angioedema, Exacerbation of endometriosis, Exacerbation of asthma, diabetes, migraine, porphyria, SLE, hepatic hemangiomas, Retinal vascular thrombosis |
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| Lactation Rating | L5 |
| Teratogenic Risk | DUAVEE (conjugated estrogens/bazedoxifene) is contraindicated in pregnancy. Estrogens may cause fetal harm; first trimester exposure is associated with congenital anomalies including cardiovascular and limb defects. Second and third trimester exposure increases risk of urogenital abnormalities and delayed cognitive development. Bazedoxifene is a selective estrogen receptor modulator; animal studies show embryotoxicity and fetotoxicity at clinically relevant doses. |
| Fetal Monitoring | Not indicated as drug is contraindicated. If inadvertent exposure, monitor fetal growth and development via ultrasound; assess for congenital anomalies postnatally. |
| Fertility Effects | May impair fertility. Estrogens can alter ovulatory function; bazedoxifene may interfere with endometrial receptivity. Effects reversible upon discontinuation. |
| Food/Dietary |
| Grapefruit juice may increase estrogen levels; avoid large amounts. No other significant food interactions. Alcohol may increase risk of liver issues; limit intake. |
| Clinical Pearls | DUAVEE (conjugated estrogens/bazedoxifene) is indicated for moderate-to-severe vasomotor symptoms and osteoporosis prevention in postmenopausal women with a uterus. Avoid in women with intact uterus who are not on a progestin; bazedoxifene is the progestin component. Contraindicated in women with undiagnosed abnormal genital bleeding, known/suspected pregnancy, breast cancer, estrogen-dependent neoplasia, active DVT/PE, or history of these conditions. Monitor for thromboembolic events. Not for use in women with prior hysterectomy. Discontinue if jaundice or visual disturbances occur. |
| Patient Advice | Take DUAVEE once daily with or without food. · This medication is for postmenopausal women with a uterus; it contains both estrogen and a progestin-like drug to protect the uterine lining. · Do not use if you have any unexplained vaginal bleeding, are pregnant, have or have had breast cancer, blood clots, or liver disease. · Report promptly any signs of blood clots (leg pain/swelling, chest pain, sudden shortness of breath) or stroke (sudden headache, vision/speech changes). · DUAVEE may increase risk of gallbladder disease, dementia (if started after age 65), and endometrial hyperplasia if the progestin component fails. · Smoking while on DUAVEE increases risk of blood clots; avoid smoking. · DUAVEE does not prevent heart attack or stroke; in fact, it may increase cardiovascular risk, especially in older women. · Store at room temperature, away from moisture and heat. · If you miss a dose, take it as soon as possible; if almost time for the next dose, skip the missed dose and resume regular schedule. Do not double dose. · You will need regular medical check-ups including mammograms and pelvic exams. |