Drug Interactions between conivaptan and gilteritinib

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of gilteritinib, which is primarily metabolized by the isoenzyme. When gilteritinib was coadministered with itraconazole, a potent CYP450 3A4 inhibitor, gilteritinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 20% and 120%, respectively, compared to administration of gilteritinib alone. Increased exposure to gilteritinib may increase the risk of serious adverse effects such as QT interval prolongation, pancreatitis, liver transaminase and bilirubin elevations, edema, infections, and stomatitis.

MANAGEMENT: Concomitant use of gilteritinib with potent CYP450 3A4 inhibitors should generally be avoided. Alternative agents with no or minimal CYP450 3A4 inhibitory potential are recommended whenever possible. Otherwise, close monitoring for increased adverse effects is advisable, including more frequent ECG monitoring. Gilteritinib treatment should be interrupted or dosage reduced in patients with serious or life-threatening toxicity in accordance with the product labeling.