Bazedoxifene + Conjugated estrogens

Indications

Bazedoxifene + Conjugated estrogens is used for: Menopausal Vasomotor Symptoms, Osteoporosis

Adult Dose

Oral Menopausal Vasomotor Symptoms Indicated for vasomotor symptoms associated with menopause 20 mg/0.45 mg (1 tablet) once daily Osteoporosis Indicated for prevention of postmenopausal osteoporosis 20 mg/0.45 mg (1 tablet) once daily

Child Dose

Renal Dose

Renal impairment: Not evaluated, and therefore not recommended

Administration

May take with or without food

Contra Indications

Undiagnosed abnormal uterine bleeding Known, suspected, or past history of breast cancer Known or suspected estrogen-dependent neoplasia Active DVT, PE, or history of these conditions Active arterial thromboembolic disease (eg, stroke, MI) or history of these conditions Hypersensitivity (eg, 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; may cause fetal harm when administered to a pregnant woman

Precautions

Women taking Bazedoxifene + Conjugated estrogens should not take additional estrogens There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens Estrogen therapy should not be used for the prevention of cardiovascular disease or dementia The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women 65 years of age and older Endometrial hyperplasia Increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens; bazedoxifene/conjugated estrogens 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. Should not take progestins, additional estrogens, or additional estrogen agonist/antagonists Estrogens and estrogen agonist/antagonists are known to increase risk of thromboembolism, including DVT, PE, and stroke Discontinue 4-6 weeks before surgery that is associated with increased risk of thromboembolism, or during periods of prolonged immobilization Retinal vascular thrombosis reported Estrogens may exacerbate pre-existing hypertriglyceridemia and lead to pancreatitis Caution with history of cholestatic jaundice associated with past estrogen use or with pregnancy Do not use with conditions that predispose to hyperkalemia Use caution in individuals with severe hypocalcemia

Pregnancy-Lactation

Pregnancy Contraindicated for use in pregnant women; not indicated for use in females of reproductive potential 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 There are no available data on bazedoxifene use in pregnant women to inform a drug associated risk of adverse developmental outcomes Based on animal data, bazedoxifene administration may adversely affect female fertility; ;owever, clinical fertility studies with bazedoxifene not conducted Animal data Animal studies have shown that oral bazedoxifene administered during period of organogenesis to pregnant rats or rabbits at 0.3 and 2 times, respectively, exposure at maximum recommended dose, can cause fetal harm; based on mechanism of action, bazedoxifene may block important functions that estrogen has during all stages of pregnancy Lactation Not indicated for use in females of reproductive potential 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 There are no data on presence of bazedoxifene in either human or animal breast milk, effect on breastfed infant, or on milk production; based on mechanism of action, bazedoxifene may block important functions that estrogen has in mammary tissue during lactation

Interactions

No drug interaction studies were conducted with Bazedoxifene + Conjugated estrogens. Estrogens are metabolized partially by CYP3A4. Concomitant use of Bazedoxifene + Conjugated estrogens with CYP3A4 inhibitors may increase the exposure of conjugated estrogens and thereby may increase the risk of endometrial hyperplasia. Contraindicated (1) ospemifene Serious - Use Alternative (27) anastrozole antithrombin alfa antithrombin III argatroban bemiparin bivalirudin carbamazepine cimetidine clarithromycin dalteparin enoxaparin erythromycin base erythromycin ethylsuccinate erythromycin lactobionate erythromycin stearate fondaparinux heparin itraconazole ketoconazole levoketoconazole nefazodone phenindione protamine quinidine rifabutin rifampin St John's Wort

Adverse Effects

Side effects of Bazedoxifene + Conjugated estrogens : 1-10% Muscle spasms (9%) Nausea (8%) Diarrhea (8%) Dyspepsia (7%) Upper abdominal pain (7%) Oropharyngeal pain (7%) Neck pain (5%) Dizziness (5%)

Mechanism of Action

Bazedoxifene: Selective estrogen receptor modulator (SERM); estrogen-like effects on bone (increase bone density) and lipids (decrease LDL); antiestrogenic in uterus and breast (reduces risk of endometrial hyperplasia that can occur with conjugated estrogens) Conjugated estrogens: Replaces endogenous estrogen