Drug Interaction Report

Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of doravirine, which is primarily metabolized by the isoenzyme. In 10 study subjects, administration of a single 50 mg dose of doravirine with the potent CYP450 3A4 inhibitor ritonavir (100 mg twice daily) increased doravirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (C24hr) by an average of 31%, 254% and 191%, respectively, compared to administration of doravirine alone. When a single 100 mg dose of doravirine was administered with ketoconazole 400 mg once daily in 10 study subjects, doravirine Cmax, AUC and C24hr increased by an average of 25%, 206% and 175%, respectively. These changes are not considered clinically significant.

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.