estrogens decreases levels of rose hips by increasing elimination. Minor/Significance Unknown.roxithromycinMonitor Closely (1)roxithromycin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Modify Therapy/Monitor Closely.rufinamideMonitor Closely (1)rufinamide will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.secobarbitalMonitor Closely (1)secobarbital will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.simvastatinMonitor Closely (1)simvastatin will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.sirolimusMonitor Closely (1)sirolimus will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.somapacitanMonitor Closely (1)bazedoxifene/conjugated estrogens decreases effects of somapacitan by Other (see comment). Modify Therapy/Monitor Closely. Comment: Oral estrogens may reduce the serum IGF-1 response to somapacitan. Patients may require higher somapacitan dosages. See drug monograph for starting dose recommendations.St John's WortMonitor Closely (1)St John's Wort will decrease the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)St John's Wort will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.streptomycinMonitor Closely (1)streptomycin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.sulfadiazineMonitor Closely (1)sulfadiazine will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.sulfamethoxazoleMonitor Closely (1)sulfamethoxazole will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.sulfisoxazoleMonitor Closely (1)sulfisoxazole will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tacrolimusMonitor Closely (1)tacrolimus will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.teicoplaninMonitor Closely (1)teicoplanin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.temocillinMonitor Closely (1)temocillin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.teniposideMonitor Closely (1)teniposide will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.tesamorelinMonitor Closely (1)tesamorelin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering metabolism. Use Caution/Monitor. May decrease efficacy; monitortetracyclineMonitor Closely (1)tetracycline will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.ticarcillinMonitor Closely (1)ticarcillin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tigecyclineMonitor Closely (1)tigecycline will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tobramycinMonitor Closely (1)tobramycin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.tolvaptanMonitor Closely (1)tolvaptan will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.topiramateMonitor Closely (1)topiramate will decrease the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.trazodoneMonitor Closely (1)trazodone will decrease the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)bazedoxifene/conjugated estrogens, trazodone. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.trimethoprimMonitor Closely (1)trimethoprim will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.trimipramineMinor (1)bazedoxifene/conjugated estrogens, trimipramine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.vancomycinMonitor Closely (1)vancomycin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.verapamilMonitor Closely (2)verapamil will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. verapamil will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.zafirlukastMonitor Closely (1)zafirlukast will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. 1-10% Muscle spasms (9%) Nausea (8%) Diarrhea (8%) Dyspepsia (7%) Upper abdominal pain (7%) Oropharyngeal pain (7%) Neck pain (5%) Dizziness (5%) Black Box Warnings Do not take additional 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 DVT in postmenopausal women (aged 50-79 years) during 7.1 years of treatment with daily oral conjugated estrogens (0.625 mg)-alone, relative to placebo The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of probable dementia in postmenopausal women >65 years during 5.2 years of treatment with daily conjugated estrogens (0.625 mg)-alone, relative to placebo; unknown whether this finding applies to younger postmenopausal women Only daily oral 0.625 mg CE was studied in the estrogen-alone substudy of the WHI; therefore, the relevance of the WHI findings regarding adverse cardiovascular events and dementia to lower CE doses, other routes of administration, or other estrogen-alone products is not known; without such data, it is not possible to definitively exclude these risks or determine the extent of these risks for other products; discuss with your patient the benefits and risks of estrogen-alone therapy, taking into account her individual risk profile Estrogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman 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 Contraindications 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 Cautions 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 Absolute risk of dementia with estrogen-alone use vs placebo from the Women’s Health Initiative was 37 versus 25 cases per 10,000 women-years; relative risk was 1.49 A 2- to 4-fold risk of gallbladder disease requiring surgery is reported in postmenopausal women receiving estrogens Retinal vascular thrombosis reported Substantial increases in blood pressure described in a small number of case reports in women receiving estrogens; this effect was not observed in a large, randomized, placebo-controlled clinical study Estrogens may exacerbate pre-existing hypertriglyceridemia and lead to pancreatitis Caution with history of cholestatic jaundice associated with past estrogen use or with pregnancy Estrogen administration leads to increased thyroid-binding globulin (TBG) levels; women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased thyroid hormone doses; patients dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of thyroid replacement therapy; these patients should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range May cause fluid retention May exacerbate asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas Estrogens are metabolized partially by CYP3A4 and therefore coadministration with inhibitors and inducers of this isoenzyme may increase risk of toxicity or alter therapeutic effect Bazedoxifene undergoes metabolism by UGT enzymes in the intestinal tract and liver; coadministration with UGT inducers may reduce bazedoxifene exposure/efficacy and therefore increase risk of endometrial hyperplasia Do not use with conditions that predispose to hyperkalemia Retinal vascular thrombosis 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, estrogens should be discontinued There are, possible risks that may be associated with use of progestins with estrogens compared to estrogen-alone regimens, including a possible increased risk of breast cancer, adverse effects on lipoprotein metabolism (e.g., lowering HDL, raising LDL), and impairment of glucose tolerance Use caution in individuals with severe hypocalcemia Malignant neoplasms Endometrial cancer: Increase risk reported with use of unopposed estrogen therapy in women with a uterus; risk is 2-12 times greater than non-users and is dependent on estrogen dose and duration; bazedoxidfene’s agonist/antagonist effect reduces risk of endometrial hyperplasia Breast cancer: No increased risk was shown in the Women’s Health Initiative randomized clinical study about breast cancer in women using estrogen-alone (conjugated estrogens 0.625 mg/day); average follow-up 7.1 yr, relative risk [RR] 0.80 Ovarian cancer: Unknown, some epidemiological showed an increased risk with use of estrogen-only products, in particular for 5 or more years; however, the duration of exposure associated with increased risk is not consistent across all epidemiologic studies, and some report no association 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 lactationPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. 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 Absorption