Drug Interaction Report

ADJUST DOSING INTERVAL: Coadministration of H2 antagonists may significantly decrease the oral bioavailability of nilotinib. The mechanism is decreased solubility of nilotinib due to increased gastric pH. Nilotinib's solubility is pH dependent and it is insoluble at a pH of 4.5 or higher. In healthy subjects, no significant change in nilotinib pharmacokinetics occurred when a single dose of nilotinib was administered 10 hours after and 2 hours before famotidine.

MANAGEMENT: During concomitant use, it is recommended to administer the H2 antagonist 10 hours before and 2 hours after the dose of nilotinib.

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.