Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of maribavir, which is primarily metabolized by the isoenzyme. When maribavir (400 mg twice daily) was administered with the potent CYP450 3A4 inducer, rifampin (600 mg once daily), maribavir peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 39% and 60%, respectively. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of maribavir should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

ADJUST DOSING INTERVAL: The presence of food may increase the absorption and toxicity of pexidartinib. Administration of pexidartinib with a high-fat meal increased peak plasma concentration (Cmax) and systemic exposure (AUC) by 100% and prolonged the time to reach peak plasma concentration (Tmax) by 2.5 hours.

GENERALLY AVOID: Grapefruit or grapefruit juice may increase the plasma concentration and risk of adverse effects of pexidartinib, including potentially fatal hepatotoxicity. The mechanism is inhibition of CYP450 3A4-mediated metabolism of pexidartinib by certain compounds present in grapefruits. Concomitant administration of itraconazole, a strong CYP450 3A4 inhibitor, increased pexidartinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 48% and 70%, respectively.

MANAGEMENT: Pexidartinib should be administered on an empty stomach, at least one hour before or two hours after a meal or snack. Consumption of grapefruit or grapefruit juice should generally be avoided during pexidartinib therapy. If concomitant use is unavoidable, the dose of pexidartinib should be reduced according to the manufacturer's recommendations. If concomitant use of grapefruit or grapefruit juice is discontinued, the dose of pexidartinib may be increased (after 3 plasma half-lives of a strong CYP450 3A4 inhibitor) to the dose that was used prior to consumption of grapefruit or grapefruit juice.