Drug Interaction Report

MONITOR: Based on in vitro inhibition data, coadministration with nilotinib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter and/or CYP450 2D6, CYP450 3A4, or UGT1A1 isoenzymes. The mechanism is decreased clearance via these routes due to inhibition by nilotinib.

MANAGEMENT: Caution is advised when nilotinib is used concurrently with drugs that are known P-gp and/or CYP450 2D6, CYP450 3A4 or UGT1A1 substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever nilotinib is added to or withdrawn from therapy.

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.