Drug Interaction Report

GENERALLY AVOID: Coadministration with moderate to potent inhibitors of CYP450 3A4 and/or inhibitors of P-glycoprotein (P-gp) efflux transporter system may increase the plasma concentrations of ensartinib, which is a substrate of both the isoenzyme and efflux transporter in vitro. Concomitant use may increase the risk and/or severity of adverse events. Clinical data characterizing the extent of this interaction and data with less potent inhibitors are not available.

MANAGEMENT: Concomitant use of ensartinib with moderate to potent inhibitors of CYP450 3A4 and/or inhibitors of P-gp should generally be avoided. Consultation with package labeling and relevant institutional protocols may be advisable for further guidance.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of nilotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because nilotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of nilotinib. The mechanism of interaction is unknown. Compared to the fast state, nilotinib systemic exposure (AUC) increased by 82% when the dose was given 30 minutes after a high-fat meal. Because nilotinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

MANAGEMENT: Patients treated with nilotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. In addition, no food should be consumed for at least 2 hours before and 1 hour after a nilotinib dose.