Conjugated Estrogen + Bazedoxifene

• Approved Indications:
• Treatment of moderate to severe vasomotor symptoms (hot flashes) associated with menopause.
• Prevention of postmenopausal osteoporosis in women at significant risk of fracture.
• Clinical Considerations:
• Indicated for use in postmenopausal women with a uterus, providing estrogen therapy while minimizing the risk of endometrial hyperplasia due to the addition of bazedoxifene, a selective estrogen receptor modulator (SERM).

• Adults:
• Oral administration is standard.
• Typical dose: One tablet daily containing conjugated estrogens 0.45 mg plus bazedoxifene 20 mg.
• Tablets should be swallowed whole, with or without food, at the same time each day.
• Special Populations:
• No specific dosage adjustments for elderly, renal, or hepatic impairment have been established; caution advised in severe hepatic impairment.
• Duration:
• Use the lowest effective dose for the shortest duration consistent with treatment goals and individual risk profiles.

Conjugated estrogens exert their effect by binding to estrogen receptors in various tissues, alleviating menopausal symptoms and preventing bone loss by regulating gene expression. Bazedoxifene acts as a selective estrogen receptor modulator (SERM), antagonizing estrogen receptors in uterine and breast tissues, thereby reducing the risk of endometrial hyperplasia and potentially breast cancer while maintaining beneficial estrogenic effects on bone and vasomotor symptoms.

• Absorption: Both conjugated estrogens and bazedoxifene are well absorbed orally.
• Distribution: Bazedoxifene is extensively bound to plasma proteins; conjugated estrogens bind to sex hormone-binding globulin (SHBG) and albumin.
• Metabolism:
• Conjugated estrogens undergo hepatic metabolism primarily by conjugation and hydroxylation.
• Bazedoxifene is metabolized by CYP3A4 enzymes, undergoing glucuronidation and excreted mainly in feces.
• Elimination:
• Bazedoxifene elimination half-life is approximately 27 hours.
• Conjugated estrogens have variable half-lives depending on individual components, generally around 13-20 hours.
• Onset: Therapeutic effects on symptoms and bone turnover are observed after weeks to months of treatment.

• Pregnancy: Category X — contraindicated due to potential teratogenicity and fetal harm.
• Lactation: Not recommended during breastfeeding due to lack of data and potential for serious adverse effects on the infant.

• Primary Class: Hormone Replacement Therapy (HRT) combined with Selective Estrogen Receptor Modulator (SERM).
• Subclass: Conjugated Estrogens + Bazedoxifene (tissue-selective estrogen complex).

• Known hypersensitivity to conjugated estrogens, bazedoxifene, or excipients.
• Undiagnosed abnormal uterine bleeding.
• Active or history of estrogen-dependent neoplasia (breast or endometrial cancer).
• History of venous thromboembolism (deep vein thrombosis, pulmonary embolism).
• Active or recent arterial thromboembolic disease (stroke, myocardial infarction).
• Severe hepatic impairment.
• Pregnancy and lactation.

• Increased risk of venous thromboembolism and stroke; monitor for symptoms and use with caution in patients with risk factors.
• Risk of endometrial hyperplasia and carcinoma is reduced compared to estrogen alone but not eliminated; monitor for abnormal bleeding.
• Increased risk of breast cancer with prolonged use.
• Monitor blood pressure, liver function, and lipid profiles periodically.
• Use the lowest effective dose for the shortest duration.
• Discontinue if jaundice, thromboembolism, or pregnancy occurs.
• Caution in patients with a history of migraines or seizure disorders.

• Common: Headache, nausea, abdominal pain, muscle spasms, diarrhea, sinusitis, vaginal bleeding or spotting, breast tenderness.
• Serious/Rare: Venous thromboembolism, stroke, myocardial infarction, breast cancer, endometrial hyperplasia, gallbladder disease, hypersensitivity reactions.

• CYP3A4 inducers (e.g., rifampin, carbamazepine) may reduce bazedoxifene and estrogen plasma levels, decreasing efficacy.
• CYP3A4 inhibitors (e.g., ketoconazole) may increase plasma concentrations, raising risk of side effects.
• May interact with anticoagulants (e.g., warfarin), altering INR values; monitor closely.
• Potential interactions with other hormonal agents and thyroid medications.

• Guidelines emphasize individualized benefit-risk assessment before initiating combined estrogen-SERM therapy.
• Recommended as an option for women with a uterus needing estrogen therapy with reduced risk of endometrial hyperplasia.
• Not recommended for primary prevention of cardiovascular disease or dementia.
• Updated safety information highlights thromboembolic risks and advises caution in at-risk populations.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container tightly closed.
• Keep out of reach of children.