Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of ixabepilone, which is primarily metabolized by the isoenzyme. According to the product labeling, administration of ixabepilone in combination with the CYP450 3A4 inhibitor ketoconazole resulted in a 79% increase in ixabepilone systemic exposure (AUC) compared to treatment without ketoconazole.

MANAGEMENT: Concomitant use of ixabepilone with potent CYP450 3A4 inhibitors should generally be avoided. If coadministration is necessary, a reduction of the ixabepilone dosage to 20 mg/m2 should be considered. Based on pharmacokinetic studies, this dosage is predicted to adjust the ixabepilone systemic exposure (AUC) to the range observed without inhibitors. However, clinical data are lacking. Following discontinuation of the potent CYP450 3A4 inhibitor, a washout period of approximately one week should be allowed before the ixabepilone dosage is adjusted upward to the indicated dosage.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ixabepilone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients treated with ixabepilone should avoid the consumption of grapefruit or grapefruit juice.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of boceprevir. When given at 800 mg three times daily with food, boceprevir exposure increased by up to 65% relative to administration in the fasting state. The bioavailability of boceprevir was similar regardless of meal type (e.g., high-fat versus low-fat) or whether taken 5 minutes prior to eating, during a meal, or immediately following completion of the meal. Therefore, boceprevir may be taken without regard to either meal type or timing of the meal.

MANAGEMENT: To ensure maximal oral absorption, boceprevir should be administered with a meal or light snack.