Drug Interaction Report

GENERALLY AVOID: The concurrent use of ospemifene with estrogens or other estrogen agonists/antagonists has not been evaluated. Safety and efficacy of this combination are unknown.

MANAGEMENT: Due to the lack of clinical data, concomitant use of ospemifene with estrogens or other estrogen agonists/antagonists is not recommended.

GENERALLY AVOID: The concurrent use of ospemifene with estrogens or other estrogen agonists/antagonists has not been evaluated. Safety and efficacy of this combination are unknown.

MANAGEMENT: Due to the lack of clinical data, concomitant use of ospemifene with estrogens or other estrogen agonists/antagonists is not recommended.

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.

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

The recommended maximum number of medicines in the 'selective estrogen receptor modulators' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'selective estrogen receptor modulators' category:

• bazedoxifene / conjugated estrogens
• ospemifene

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.