Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may 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. The interaction has not been studied with other, less potent inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of quizartinib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

ADJUST DOSING INTERVAL: Food increases the systemic exposure to both telotristat ethyl and its active metabolite, telotristat. Following administration of a single 500 mg dose of telotristat ethyl (twice the recommended dose) with a high-fat meal, telotristat ethyl peak plasma concentration (Cmax) and systemic exposure (AUC) were 112% and 264% higher, respectively, compared to administration under fasted conditions. The Cmax and AUC values for telotristat were also increased by 47% and 33%, respectively. The in vitro inhibitory potency of telotristat towards tryptophan hydroxylase has been shown to be approximately 29 times higher than that of the parent drug.

MANAGEMENT: Telotristat ethyl should be administered with food.