Drug Interaction Report

MONITOR: Coadministration with etravirine may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is accelerated clearance due to induction of CYP450 3A4 activity by etravirine. In 15 study subjects coadministered etravirine and the CYP450 3A4 substrate sildenafil (50 mg single dose), sildenafil peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 45% and 57%, respectively, while Cmax and AUC of its active N-desmethyl metabolite decreased by 25% and 41%, respectively.

MANAGEMENT: Caution is advised if etravirine must be used concomitantly with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever etravirine is added to or withdrawn from therapy.

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.