Drug Interaction Report

GENERALLY AVOID: Coadministration with voriconazole may increase the plasma concentrations of telaprevir. The mechanism involves voriconazole inhibition of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of telaprevir. The interaction has not been specifically studied with voriconazole, but has been reported with another azole antifungal agent. In 17 study subjects, administration of a single 750 mg dose of telaprevir in combination with a single 400 mg dose of ketoconazole resulted in an average 24% increase in telaprevir peak plasma concentration (Cmax) and 62% increase in systemic exposure (AUC) compared to administration alone. The effect of telaprevir on the pharmacokinetics of voriconazole is unknown. Because telaprevir is also an inhibitor of CYP450 3A4, it may increase the plasma concentrations of voriconazole. However, due to multiple isoenzymes involved in voriconazole metabolism, the potential interaction with telaprevir is difficult to predict.

MANAGEMENT: Voriconazole should not be administered to patients receiving telaprevir unless the benefits are anticipated to outweigh the risks.

ADJUST DOSING INTERVAL: Food reduces the oral absorption and bioavailability of voriconazole. According to the product labeling, administration of multiple doses of voriconazole with high-fat meals decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 34% and 24%, respectively, when the drug is administered as a tablet, and by 58% and 37%, respectively, when administered as the oral suspension.

MANAGEMENT: To ensure maximal oral absorption, voriconazole tablets and oral suspension should be taken at least one hour before or after a meal.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of telaprevir. When given with a meal containing 533 kcal and 21 g fat, telaprevir systemic exposure (AUC) increased by 237% compared to administration under fasting conditions. The type of meal also affects the exposure to telaprevir. Relative to fasting, telaprevir AUC increased by approximately 117% with a low-fat meal (249 kcal; 3.6 g fat) and 330% with a high-fat meal (928 kcal; 56 g fat). In Phase 3 clinical trials, telaprevir doses were administered within 30 minutes of completing a meal or snack containing approximately 20 grams of fat.

MANAGEMENT: Telaprevir should be administered with food containing approximately 20 grams of fat. Patients should be advised that the fat content of the meal or snack is critical to the absorption of telaprevir. Food taken with telaprevir should be ingested within 30 minutes prior to each dose. Examples of some foods that could be taken with telaprevir include: bagel with cream cheese; half cup of nuts; 3 tablespoons of peanut butter; 1 cup of ice cream; 2 ounces of American or cheddar cheese; 2 ounces of potato chips; or half cup of trail mix.