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: Food may reduce as well as delay the absorption of dabrafenib. In study subjects, administration of dabrafenib with a high-fat meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 51% and 31%, respectively, and delayed median Tmax by approximately 3.6 hours compared to administration in the fasted state.

MANAGEMENT: Dabrafenib should be taken at least 1 hour before or 2 hours after a meal.

The recommended maximum number of medicines in the 'multikinase inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'multikinase inhibitors' category:

• dabrafenib
• quizartinib

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.