Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of nilotinib, which is primarily metabolized by the isoenzyme. In healthy subjects receiving the potent CYP450 3A4 inducer rifampin (600 mg once daily for 12 days), nilotinib systemic exposure (AUC) was reduced by approximately 80%. Data are not available for nilotinib in combination with other, less potent CYP450 3A4 inducers.

MANAGEMENT: Patients receiving nilotinib with CYP450 3A4 inducers should be monitored for potentially diminished pharmacologic response to nilotinib. Concomitant use should be avoided if an interaction is suspected.

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.