Ospemifene

• Vulvar and Vaginal Atrophy (VVA):
  Treatment of moderate to severe dyspareunia (painful intercourse), a symptom of vulvar and vaginal atrophy due to menopause.
• Off-label Uses:
  Occasionally used to manage other menopausal symptoms related to estrogen deficiency under clinical discretion.

• Route: Oral (tablet).
• Adults (Postmenopausal Women):
• Recommended dose: 60 mg once daily, taken with food to improve absorption.
• Treatment duration: Based on clinical response; safety beyond 12 months has not been established.
• Elderly:
• No specific dose adjustment needed.
• Renal or Hepatic Impairment:
• Use with caution in severe hepatic impairment; dose adjustment not well established.
• No dosage adjustment recommended in mild to moderate renal impairment.
• Pediatrics:
• Not indicated.

Ospemifene is a selective estrogen receptor modulator (SERM) that acts as an estrogen agonist on the vaginal epithelium, promoting the restoration of the normal structure and function of vaginal tissues. It binds to estrogen receptors (ERα and ERβ) in target tissues, inducing gene expression that supports epithelial proliferation, increased lubrication, and improved elasticity. Unlike estrogen, ospemifene has tissue-selective effects, exhibiting antagonistic or neutral activity in other estrogen-responsive tissues such as the breast.

• Absorption:
• Well absorbed orally; peak plasma concentrations reached within 2 to 4 hours post-dose.
• Bioavailability:
• Approximately 60% after oral administration.
• Distribution:
• Highly protein-bound (~99%), mainly to albumin.
• Metabolism:
• Extensively metabolized in the liver primarily via CYP3A4 and CYP2C9 isoenzymes.
• Half-life:
• Approximately 26 hours, allowing once-daily dosing.
• Elimination:
• Excreted mainly via feces; minor urinary elimination.

• Pregnancy:
• FDA Category X — Contraindicated during pregnancy due to potential for fetal harm.
• Lactation:
• Unknown if excreted in human milk; breastfeeding not recommended during treatment.

• Selective Estrogen Receptor Modulator (SERM).

• Known hypersensitivity to ospemifene or any of its components.
• Undiagnosed abnormal vaginal bleeding.
• History of or current venous thromboembolism (e.g., deep vein thrombosis, pulmonary embolism).
• Active or history of arterial thromboembolic disease (e.g., stroke, myocardial infarction).
• Known or suspected estrogen-dependent neoplasia.
• Pregnancy or breastfeeding.

• Increased risk of thromboembolic events; use with caution in patients with risk factors such as smoking, obesity, or immobilization.
• Monitor for signs of stroke, myocardial infarction, and deep vein thrombosis.
• Use with caution in patients with hepatic impairment.
• Regular gynecological evaluations recommended to monitor for endometrial hyperplasia or malignancy.
• Patients should report any unusual vaginal bleeding immediately.
• Potential for hot flashes or sweating.

• Common:
• Hot flashes, vaginal discharge, muscle spasms, excessive sweating, genital discharge.
• Less Common/Serious:
• Thromboembolic events (rare but serious), leg cramps, headache, dizziness.
• Timing & Severity:
• Hot flashes often occur early during treatment; thromboembolic events are rare but require immediate medical attention.

• CYP3A4 Inducers (e.g., rifampin, carbamazepine):
• May reduce ospemifene plasma levels, decreasing efficacy.
• CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin):
• May increase ospemifene plasma concentrations, increasing risk of adverse effects.
• Anticoagulants:
• Use cautiously; ospemifene may affect coagulation parameters.
• Hormonal therapies:
• Concurrent use with estrogen-containing products not recommended.

• Continued approval for dyspareunia related to menopausal vulvar and vaginal atrophy.
• No major changes in dosing or safety warnings in recent guidelines from FDA or international regulatory agencies.
• Emphasis on thromboembolic risk and need for patient education on signs and symptoms.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in tightly closed containers.
• Do not freeze.