Dosing & Uses
Dosage Forms & Strengths
Menopausal Vasomotor Symptoms
Indicated for vasomotor symptoms associated with menopause
20 mg/0.45 mg (1 tablet) PO qDay
Indicated for prevention of postmenopausal osteoporosis in nonhysterectomized women; when prescribing solely for the prevention of postmenopausal osteoporosis, therapy should only be considered for women at significant risk and nonestrogen medication should be carefully considered
20 mg/0.45 mg (1 tablet) PO qDay
Take supplemental calcium and/or vitamin D if daily intake is inadequate
Renal impairment: Not evaluated, and therefore not recommended
Hepatic impairment: Contraindicated
Should be used for the shortest duration consistent with treatment goals and risks for the individual woman
May take with or without food
Swallow tablet whole, do not chew, crush, or split
If a dose is missed, instruct patients to take it as soon as remembered unless it is almost time for the next scheduled dose; do not take 2 doses at the same time
Serious - Use Alternative
Significant - Monitor Closely
Muscle spasms (9%)
Upper abdominal pain (7%)
Oropharyngeal pain (7%)
Neck pain (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
Estrogens should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman
- 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
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
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
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
- 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 & Lactation
Pregnancy Category: X
Lactation: Contraindicated; 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
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
Bioavailability: Readily absorbed
Food effect: High fat/high calorie meal increases absolute bioavailability of bazedoxifene by 25%
Following multiple doses of bazedoxifene/conjugated estrogens (CE) at Day 10
- Peak plasma time: 6.5 hr (CE); 2.5 hr (bazedoxifene)
- Peak plasma concentration: 2.6 ng/mL; 6.9 ng/mL (bazedoxifene)
- AUC at steady state: 35 ng•hr/mL (CE): 71 ng•hr/mL (bazedoxifene)
Distribution of conjugated estrogens/bazedoxifene has not been studied; following results are from monotherapy studies
- Wide distribution with higher concentrations in sex hormone target organs
- Highly bound to sex hormone binding globulin (SHBG) and albumin
Bazedoxifene (3 mg IV dose)
- VD: 14.7 L/kg
- Highly bound to plasma proteins (98-99%); does not bind to SHBG
Metabolism of conjugated estrogens/bazedoxifene has not been studied; following results are from monotherapy studies
- Metabolized in the liver to glucuronide and sulfate conjugates
- Major metabolites: estradiol, estrone, and estriol
Bazedoxifene (20 mg PO dose)
- Extensive glucuronidation
- After administration of single dose of conjugated estrogens/bazedoxifene at steady state concentration by 2nd week of once daily dosing CE, baseline-adjusted total estrone: 17 hr
- Bazedoxifene: 30 hr
- Results of monotherapy studies
- Conjugated estrogens: Urine excretion of metabolites
- Bazedoxifene (20 mg PO dose): Biliary excretion is major route; 85% feces, <1% urine
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