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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever letermovir is added to or withdrawn from therapy.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.