Drug Interaction Report

GENERALLY AVOID: Coadministration with inducers of the P-glycoprotein (P-gp) efflux transporter and/or the uridine diphosphate glucuronosyltransferase (UGT) enzymes may decrease the plasma concentrations of letermovir according to the product labeling. Because letermovir is a substrate of P-gp and UGT 1A1 and 1A3, induction of the efflux transporter and metabolic enzymes may theoretically increase the clearance of letermovir. Concomitant use of rifampin initially resulted in a clinically insignificant increase in letermovir plasma concentrations (due to inhibition of organic anion transporting polypeptide [OATP] 1B1/3 and/or P-gp), followed by clinically significant decreases in letermovir plasma concentrations with continued rifampin coadministration (due to induction of P-gp/UGT).

MANAGEMENT: Due to the potential loss of efficacy, use of letermovir with inducers of the P-glycoprotein (P-gp) efflux transporter and/or the uridine diphosphate glucuronosyltransferase (UGT) enzymes is not recommended.

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.