Drug Interaction Report

Theoretically, coadministration with inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may decrease the plasma concentrations of rivaroxaban, which is a substrate of the isoenzyme as well as the efflux transporter. In a pharmacokinetic study, administration of a single 20 mg dose of rivaroxaban with the potent CYP450 3A4 and P-gp inducer rifampin (titrated up to 600 mg once daily) resulted in approximately 22% and 50% decreases in mean rivaroxaban peak plasma concentration (Cmax) and system exposure (AUC), respectively, with parallel decreases in its pharmacodynamic effects. The effects of less potent inducers of either CYP450 3A4 or P-gp have not been studied.

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.