Drug Interactions between letermovir and Talicia

MONITOR: Coadministration with letermovir may decrease the plasma concentrations of drugs that are metabolized by CYP450 2C9 and/or 2C19. The interaction has been studied with voriconazole, a substrate of CYP450 2C9 and 2C19. According to the product labeling, voriconazole peak plasma concentration (Cmax), systemic exposure (AUC) and concentration at 12 hours postdose (C12hr) decreased by an average of 39%, 44% and 51%, respectively, when voriconazole 200 mg orally twice daily was coadministered with letermovir 480 mg orally once daily.

MANAGEMENT: Caution is advised when letermovir is used concomitantly with drugs that are substrates of CYP450 2C9 and/or 2C19, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever letermovir is added to or withdrawn from therapy.

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.