This tablet pairs conjugated estrogens with bazedoxifene. Conjugated estrogens and bazedoxifene function by binding to and activating estrogen receptors (ER) α and β, which vary in proportion from tissue to tissue. Conjugated estrogens are composed of multiple estrogens and are agonists of ER- α and β. Bazedoxifene is an estrogen agonist/antagonist that acts as an agonist in some estrogen-sensitive tissues and an antagonist in others (e.g., uterus). The pairing of conjugated estrogens with bazedoxifene produces a composite effect that is specific to each target tissue. The bazedoxifene component reduces the risk of endometrial hyperplasia that can occur with the conjugated estrogens component.

This is a combination of conjugated estrogens with an estrogen agonist/antagonist indicated for 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 or past history of venous thromboembolism
• Active or past history of arterial thromboembolism
• Hypersensitivity (angioedema, anaphylaxis) 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

In four prospective, randomized, placebo-controlled trials the common adverse reactions (incidence ≥5%) were muscle spasms, nausea, diarrhea, dyspepsia, abdominal pain upper, oropharyngeal pain, dizziness, and neck pain.

Overdose Effects

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.

• Women taking this tablet should not take progestins, additional estrogens or additional estrogen agonist/antagonists
• Cardiovascular disorders, including venous thromboembolism, pulmonary embolism, stroke, and retinal vascular thrombosis
• Malignant neoplasms, including endometrial cancer, breast cancer, and ovarian cancer
• Estrogens increase the risk of gallbladder disease
• Discontinue estrogen if loss of vision, severe hypertriglyceridemia or cholestatic jaundice occurs
• Monitor thyroid function in women on thyroid replacement therapy

Use in Special Populations

Pediatric Use: This tablet is not indicated for use in children.

Geriatric Use: This tablet was not studied in women aged 75 or older; use in this population is not recommended. An increased risk of probable dementia in women over 65 years of age was reported in the Women’s Health Initiative Memory ancillary studies of the Women’s Health Initiative.

Renal Impairment: This tablet was not studied in women with renal impairment; use in this population is not recommended.

Body Mass Index: Women with BMI >27 kg/m 2 may have an increased risk of endometrial hyperplasia.

Pregnancy & Lactation

Pregnancy Category X. This tablet must not be used in women who are or may become pregnant. No studies were performed on animals to evaluate the effects on reproduction with conjugated estrogens/bazedoxifene. This tablet should not be used by lactating women. 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