Presentation and Status in Health Basket
Treatment of Moderate to Severe Vasomotor Symptoms Associated with Menopause: The recommended dosage is one DUAVIVE tablet daily.
Prevention of Postmenopausal Osteoporosis: The recommended dosage is one DUAVIVE tablet daily.
General Dosing Information: Take DUAVIVE once daily, without regard to meals. Tablets should be swallowed whole.
Recommendations for Calcium and Vitamin D Supplementation: Women taking DUAVIVE for prevention of postmenopausal osteoporosis should add supplemental calcium and/or vitamin D to their diet if daily intake is inadequate.
Administration Instructions for Missed Doses: If a dose of DUAVIVE 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.
Use in Patients with Renal Impairment: The pharmacokinetics of DUAVIVE have not been evaluated in patients with renal impairment. Use in patients with renal impairment is not recommended.
Use in the Elderly: DUAVIVE has not been studied in women over 75 years of age. Use in women over 75 years of age is not recommended.
Treatment of the following conditions in women with a uterus: Treatment of moderate to severe vasomotor symptoms associated with menopause. Prevention of postmenopausal osteoporosis.
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, women who may become pregnant, and nursing mothers. this formulation may cause fetal harm when administered to a pregnant woman. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
Women taking this drug should not take progestins, additional estrogens or additional estrogen agonist/antagonists. Estrogen agonist/antagonists (including bazedoxifene, a component of this formulation) 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, this formulation 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.
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.
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.
Breast cancer: The use of estrogen-alone has been reported to result in an increase in abnormal mammograms requiring further evaluation. The effect of treatment with this formulation 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. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results.
Ovarian Cancer: A meta-analysis of 17 prospective and 35 retrospective epidemiology studies found that women who used hormonal therapy for menopausal symptoms had an increased risk for ovarian cancer. The primary analysis, using case-control comparisons, included 12,110 cancer cases from the 17 prospective studies. The relative risks associated with current use of hormonal therapy was 1.41 (95% confidence interval [CI] 1.32 to 1.50); there was no difference in the risk estimates by duration of the exposure (less than 5 years [median of 3 years] vs. greater than 5 years [median
of 10 years] of use before the cancer diagnosis). The relative risk associated with combined current and recent use (discontinued use within 5 years before cancer diagnosis) was 1.37 (95% CI 1.27-1.48), and the elevated risk was significant for both estrogen-alone and estrogen plus progestin products. The exact duration of hormone therapy use associated with an increased risk of ovarian cancer, however, is unknown. The effect of treatment with DUAVIVE on the risk of ovarian cancer is unknown.
Gallbladder Disease: A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported.
Elevated Blood Pressure: In a small number of case reports in women receiving estrogens, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens.
Hypertriglyceridemia: In women with pre-existing hypertriglyceridemia, treatment with estrogens may be associated with elevations of plasma triglycerides leading to pancreatitis.
Visual Abnormalities: Retinal vascular thrombosis has been reported in patients receiving estrogens. Discontinue medication pending examination if there is sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, this formulation should be permanently discontinued.
Hepatic Impairment and Past History of Cholestatic Jaundice: This formulation 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.
See prescribing information for full details.
The most commonly observed adverse reactions (incidence ≥ 5%) more frequently reported in women treated with DUAVIVE than placebo are:
Gastrointestinal disorders: Nausea, Diarrhea, Dyspepsia, Abdominal pain upper.
Musculoskeletal and connective tissue disorders: Muscle spasms, Neck pain.
Nervous system disorders: Dizziness.
Respiratory, thoracic, and mediastinal disorders: Oropharyngeal pain.
See prescribing information for full details.
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 this drug, 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 this formulation 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.
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.
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.
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.
Pregnancy and Lactation
Pregnancy: must not be used in women who are or may become pregnant.
Lactation: It is not known whether this drug is excreted in human milk. Detectable amounts of estrogens have been identified in the milk of mothers receiving conjugated estrogens. Estrogen administration to nursing mothers has been shown to decrease the quantity and quality of the milk.
See prescribing information for full details.
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.
Storage: Do not store above 25ºC.
Lactose: contains lactose.