Drug Interaction Report

GENERALLY AVOID: Coadministration with inhibitors of the organic anion transporting polypeptide (OATP) 1B3 hepatic uptake transporter and/or the hepatic bile acid uptake transporter sodium taurocholate co-transporting polypeptide (NTCP) may significantly increase the plasma concentrations and effects of zavegepant, which is a substrate of these transporters. When single-dose oral zavegepant (100 mg) was administered with the OATP 1B3 and NTCP inhibitor and strong CYP450 3A4 inducer, rifampin, at steady state, zavegepant peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 2.2- and 2.3-fold, respectively.

MANAGEMENT: Concomitant use of zavegepant with OATP 1B3 and/or NTCP inhibitors should generally be avoided.

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.