Drug Interaction Report

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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever letermovir is added to or withdrawn from therapy.

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of zafirlukast. In two separate studies, one using a high-fat and the other a high-protein meal, administration of zafirlukast with food reduced the mean bioavailability by approximately 40%.

MANAGEMENT: To ensure maximal oral absorption, zafirlukast should be administered at least 1 hour before or 2 hours after meals.