Drug Interaction Report

GENERALLY AVOID: Coadministration with fluconazole may significantly increase the plasma concentrations of ospemifene. The proposed mechanism is fluconazole inhibition of ospemifene metabolism via CYP450 3A4, 2C9, and 2C19. In 14 postmenopausal women given fluconazole 400 mg once followed by 200 mg daily for a total duration of 8 days, administration of ospemifene 60 mg after breakfast on day 5 of fluconazole treatment resulted in 1.7- and 2.7-fold increases in ospemifene peak plasma concentration (Cmax) and systemic exposure (AUC), respectively, compared to administration of ospemifene alone. Increased risk of adverse events such as hot flush, thromboembolism, and endometrial or breast cancer may occur.

MANAGEMENT: Ospemifene should not be prescribed in combination with fluconazole.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of ospemifene. In a cross-study comparison, administration of a single 60 mg dose of ospemifene with a high-fat/high-calorie meal (860 kcal) in postmenopausal women increased ospemifene peak plasma concentration (Cmax) and systemic exposure (AUC) by 2.3- and 1.7-fold, respectively, compared to administration under fasted condition. Elimination half-life and time to maximum concentration (Tmax) were not altered. In two separate food effect studies where different ospemifene tablet formulations were given to healthy male volunteers, ospemifene Cmax and AUC increased by 2.3- and 1.8-fold, respectively, with a low-fat/low-calorie meal (300 kcal) and 3.6- and 2.7-fold, respectively, with a high-fat/high-calorie meal (860 kcal) relative to fasting.

MANAGEMENT: Ospemifene should be taken once daily with food.