Bazedoxifene Acetate

General

• Use for shortest duration consistent with treatment goals and risks for the individual woman.1 Reevaluate patients periodically to determine if continued treatment is necessary.1

• When used for prevention of osteoporosis, use supplemental calcium and/or vitamin D concomitantly if daily dietary intake is considered inadequate.1

Administration

Oral Administration

Administer orally without regard to meals.1

Swallow tablets whole.1

Dosage

Available as bazedoxifene acetate; dosage expressed in terms of bazedoxifene.1

Each tablet of bazedoxifene/conjugated estrogens in fixed combination contains bazedoxifene 20 mg and conjugated estrogens 0.45 mg.1

Adults

Bazedoxifene 20 mg in fixed combination with conjugated estrogens 0.45 mg once daily.1

Bazedoxifene 20 mg in fixed combination with conjugated estrogens 0.45 mg once daily.1

Special Populations

When bazedoxifene is used in fixed combination with conjugated estrogens, dosage requirements for conjugated estrogens should be considered.1

Hepatic Impairment

Bazedoxifene/conjugated estrogens in fixed combination: Contraindicated.1 (See Contraindications and Hepatic Effects under Cautions.)

Renal Impairment

Bazedoxifene/conjugated estrogens in fixed combination: Not recommended.1

Absorption

Bioavailability

Approximately 6%.1

Peak bazedoxifene concentrations attained at approximately 2.5 hours after a dose of bazedoxifene/conjugated estrogens in fixed combination.1

Food

Bazedoxifene AUC increased by 25% when bazedoxifene/conjugated estrogens in fixed combination administered with a high-fat, high-calorie meal;1 peak concentrations not affected by food.1

Special Populations

Geriatric patients: Following single 20-mg dose of bazedoxifene, AUC increased 1.5-fold in women 65–74 years of age and 2.6-fold in those ≥75 years of age compared with women 51–64 years of age.1

Hepatic impairment: Pharmacokinetics of bazedoxifene/conjugated estrogens in fixed combination not studied.1 Following single 20-mg dose of bazedoxifene, peak concentrations and AUC substantially increased in women with mild, moderate, or severe hepatic impairment.1 (See Contraindications and Hepatic Effects under Cautions.)

Renal impairment: Pharmacokinetics of bazedoxifene/conjugated estrogens in fixed combination not studied.1

Distribution

Plasma Protein Binding

Highly bound (98–99%);1 does not bind to SHBG.1

Elimination

Metabolism

Extensively metabolized by glucuronidation;1 little or no metabolism mediated by CYP isoenzymes.1 Major metabolite is bazedoxifene-5-glucuronide;1 plasma concentrations of metabolite approximately tenfold higher than those of unchanged drug.1

Elimination Route

Expected to undergo enterohepatic recycling from gut to systemic circulation.1 Excreted in bile followed by elimination in feces (85%);1 <1% eliminated in urine.1

Half-life

Approximately 30 hours.1

Special Populations

Severe hepatic impairment (Child-Pugh class C): After single 20-mg dose of bazedoxifene, half-life prolonged to 50 hours.1

• Tissue-selective, estrogen agonist-antagonist;1 25 also referred to as a selective estrogen receptor modulator (SERM).3 5 6 9

• Binds to estrogen receptor (ER) α and ERβ;1 11 25 slightly stronger binding occurs at ERα receptor.20 24

• Activates estrogenic pathways in some tissues and blocks these pathways in other tissues.1

• Exhibits estrogen antagonistic effects on endometrium when given alone and concomitantly with conjugated estrogens (e.g., no substantial effect on endometrial thickness or endometrial hyperplasia).9 11 12 13 16 17 21 25 26

• In vitro, limited estrogen agonistic effects on human breast cancer cells, blocks stimulatory actions of estradiol and conjugated estrogens on breast cells, and reverses negative effects of estrogen in breast cancer cells.11 18 20 25 26

• Shown to increase bone mass in animal models and in clinical studies.11 14 15 24

• Combination of a SERM (e.g., bazedoxifene) and estrogens also referred to as a tissue-selective estrogen complex (TSEC).3 4 5 6 26

• Fixed combination of bazedoxifene/conjugated estrogens produces composite effect specific to each target tissue;1 26 bazedoxifene component reduces risk of endometrial hyperplasia associated with use of conjugated estrogens alone.1

Initial dose: Bazedoxifene-conjugated estrogens 20 mg-0.45 mg tablet orally daily
Duration of therapy: Bazedoxifene-conjugated estrogens should be for the shortest duration consistent with treatment goals and risks for the patient.

Approved indication: Treatment of Moderate to Severe Vasomotor Symptoms Associated with Menopause and
Prevention of Postmenopausal Osteoporosis.

Data not available

Bazedoxifene-conjugated estrogens should not be used in lactating women. Excreted into human milk: Unknown (bazedoxifene); Yes (estrogen) Excreted into animal milk: Data not available The effects in the nursing infant are unknown. Estrogen administered to nursing women decreases the quantity and quality of the milk.