Drug Interaction Report

ADJUST DOSE: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of atogepant, which is primarily metabolized by the isoenzyme. When atogepant was administered in healthy study subjects with steady-state rifampin, a potent CYP450 3A4 inducer, atogepant peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 30% and 60%, respectively. No dedicated drug interaction studies were conducted to assess concomitant use with moderate CYP450 3A4 inducers, but reduced atogepant exposure would be expected.

MANAGEMENT: The recommended dosage of atogepant is 30 mg or 60 mg once daily when used concomitantly with potent or moderate CYP450 3A4 inducers.

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.