Drug Interaction Report

GENERALLY AVOID: Coadministration with drugs that are combined P-glycoprotein (P-gp) and moderate inducers of CYP450 3A4 or sole moderate inducers of CYP450 3A4 may decrease the plasma concentrations of lenacapavir and result in a potential loss of virologic response. The proposed mechanism is increased clearance due to induction of the isoenzyme CYP450 3A4, which is partly responsible for the metabolism of lenacapavir and induction of the P-gp transporter of which lenacapavir is a substrate. In pharmacokinetic studies conducted in fasted subjects without HIV, coadministration of a single oral dose of lenacapavir 300 mg with the combined P-gp and moderate inducer of CYP450 3A4 efavirenz 600 mg once daily decreased the systemic exposure (AUC) and peak plasma concentration (Cmax) of lenacapavir by approximately 56% and 36%, respectively.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, concomitant use of lenacapavir with drugs that are combined P-gp and moderate inducers of CYP450 3A4 or sole moderate inducers of CYP450 3A4 should generally be avoided.

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.