Drug Interaction Report

GENERALLY AVOID: Coadministration of etravirine and protease inhibitors without concomitant ritonavir as a pharmacokinetic booster may produce significant alterations in plasma concentrations of the protease inhibitor. Etravirine is an inducer of CYP450 3A4 and inhibitor of CYP450 2C19 and 2C9, thus it may variously affect the metabolism and clearance of protease inhibitors. In unboosted pharmacokinetic regimens, etravirine has reduced plasma levels of atazanavir and indinavir and increased levels of amprenavir and nelfinavir. However, significant interactions affecting either etravirine and/or protease inhibitor plasma concentrations have also been observed with boosted regimens, including atazanavir/ritonavir, fosamprenavir/ritonavir, and tipranavir/ritonavir.

MANAGEMENT: Protease inhibitors should not be prescribed with etravirine in the absence of low-dose ritonavir as a pharmacokinetic booster.

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.