Drug Interaction Report

MONITOR: Coadministration with moderate inducers of CYP450 3A4 may decrease the plasma concentrations of rolapitant, which is primarily metabolized by the isoenzyme. When the potent CYP450 3A4 inducer rifampin was administered at 600 mg once daily for 7 days before and 7 days after a single 180 mg dose of rolapitant, mean rolapitant peak plasma concentration (Cmax) and systemic exposure decreased by 30% and 85%, respectively, compared to administration of rolapitant alone. Mean half-life of rolapitant decreased from 176 hours to 41 hours with rifampin. No data are available for other, less potent CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of rolapitant should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of etravirine. The mechanism is unknown. Compared to administration following a meal, the systemic exposure (AUC) to etravirine was decreased by about 50% when the drug was administered under fasting conditions. The types of meal studied (ranging from 345 kilocalories containing 17 grams fat to 1160 kilocalories containing 70 grams fat) did not appear to make a difference with respect to impact on etravirine bioavailability.

MANAGEMENT: Etravirine should always be administered following a meal.