Drug Interaction Report

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of quizartinib and its major circulating active metabolite, AC886. According to the prescribing information, quizartinib is primarily metabolized via oxidation by CYP450 3A4/5 in vitro, and AC886 is formed and metabolized by CYP450 3A4/5. Following coadministration of a single 53 mg dose of quizartinib with efavirenz, a moderate CYP450 3A4 inducer, quizartinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 45% and 90%, respectively, while the Cmax and AUC of AC886 decreased by 68% and 96%, respectively. Reduced effectiveness of quizartinib may occur. Coadministration with a potent CYP450 3A4 inducer has not been studied, but similar if not even greater reductions in quizartinib and AC886 exposures should be expected.

MANAGEMENT: Concomitant use of quizartinib with potent or moderate CYP450 3A4 inducers should generally be avoided.

ADJUST DOSING INTERVAL: Certain penicillins may exhibit reduced gastrointestinal absorption in the presence of food. The therapeutic effect of the antimicrobial may be reduced.

MANAGEMENT: The interacting penicillin should be administered one hour before or two hours after meals. Penicillin V and amoxicillin are not affected by food and may be given without regard to meals.