Drug Interaction Report

MONITOR: Coadministration of etravirine with a drug that is both a substrate as well as inducer of CYP450 3A4 may result in decreased plasma concentrations of both drugs. Etravirine itself is also a substrate and inducer of CYP450 3A4. Theoretically, metabolism of etravirine and the coadministered drug may be mutually induced when used in combination.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, caution is advised if etravirine is prescribed in combination with a drug that is an inducer of CYP450 3A4. Close clinical and laboratory monitoring of antiretroviral response is recommended. In addition, dosage adjustments may be required for the coadministered drug if it is also a substrate of CYP450 3A4.

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.