Drug Interaction Report

Coadministration with mild or moderate inhibitors of CYP450 3A4 is not expected to have clinically significant effects on the pharmacokinetics of quizartinib or 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 ketoconazole, a potent CYP450 3A4 inhibitor, quizartinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 17% and 94%, respectively, while the Cmax and AUC of AC886 decreased by 60% and 94%, respectively. By contrast, clinically significant changes in the Cmax and AUC of quizartinib and AC886 were not observed following coadministration of single-dose quizartinib with fluconazole, a moderate CYP450 3A4 inhibitor. Therefore, no dosage adjustments are recommended when quizartinib is coadministered with mild and moderate CYP450 3A4 inhibitors.

MONITOR: Due to their gastrointestinal pharmacologic effects, somatostatin analogs (e.g., octreotide, lanreotide) may variously affect the absorption of dietary nutrients and concomitantly administered oral medications. Somatostatin analogs have been shown to prolong gastrointestinal transit time and inhibit intestinal absorption of some nutrients such as fat. Clinical data are limited, however. In case reports, octreotide has been reported to reduce the relative bioavailability of cyclosporine. Transplant rejection and significant reductions in cyclosporine levels, sometimes to undetectable levels, have been reported in association with the interaction. Vitamin K absorption was not affected when concomitantly administered with lanreotide according to the manufacturer.

MANAGEMENT: Clinicians should be aware of the potential for altered absorption of concomitantly administered oral medications during treatment with somatostatin analogs. Blood levels and clinical response should be monitored, particularly for drugs that have a narrow therapeutic index, and the dosages adjusted as necessary.