Drug Interaction Report

GENERALLY AVOID: Coadministration with strong CYP450 3A4 inhibitors may increase plasma concentrations of thiotepa, and decrease concentrations of its active metabolite triethylenephosphoramide (TEPA). Thiotepa is a prodrug that is primarily converted to TEPA by the isoenzyme. A pharmacokinetic study evaluating six breast cancer patients receiving high-dose chemotherapy (cyclophosphamide 1,500 mg/m2/day, thiotepa 120 mg/m2/day, and carboplatin AUC 5 mg min/mL/day) with the moderate CYP450 3A4 inhibitor aprepitant (125 mg one day before chemotherapy, then 80 mg daily during and for three days after) showed a 15% increase in total thiotepa exposure, a 33% decrease in TEPA formation, and 20% reduction in TEPA exposure. Although clinical evidence is limited, strong CYP450 3A4 inhibitors may more significantly increase thiotepa exposure and reduce TEPA exposure, potentially resulting in more thiotepa-related adverse effects and reduced efficacy.

MANAGEMENT: The use of thiotepa in combination with strong CYP450 3A4 inhibitors should generally be avoided. If concomitant use of a strong CYP450 3A4 inhibitor is required, it is recommended that patients be carefully monitored for reduced efficacy and thiotepa-related toxicities such as myelosuppression, cutaneous toxicity, and neurotoxicity.

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.