Drug Interaction Report

MONITOR: Ospemifene and its major metabolite, 4-hydroxyospemifene, may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of organic cation transporter (OCT)1, uridine diphosphate glucuronosyltransferase (UGT) 1A3, and/or UGT1A9. The proposed mechanism, based on in vitro data, is decreased clearance due to ospemifene-mediated inhibition of OCT1, UGT1A3, and/or UGT1A9.

MANAGEMENT: Until more information is available, caution is advised when ospemifene is used concomitantly with drugs that are substrates of OCT1, UGT1A3, and/or UGT1A9, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ospemifene is added to or withdrawn from therapy with these drugs. Patients should be monitored for the development of adverse effects.

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.