Drug Interaction Report

MONITOR: Coadministration of orlistat with ospemifene may result in a reduction in the bioavailability and therapeutic effects of ospemifene. By partially inhibiting the absorption of dietary fat, orlistat may indirectly reduce the gastrointestinal absorption of ospemifene, which is lipophilic in nature.

MANAGEMENT: Caution is advised if orlistat and ospemifene are used in combination. Patients should be monitored for clinical evidence of altered ospemifene efficacy. Separating the doses of orlistat and ospemifene by at least 2 hours may help minimize the potential for an interaction.

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.