Drug Interaction Report

ADJUST DOSING INTERVAL: Antacids significantly decrease the oral bioavailability of nilotinib. The mechanism is decreased solubility of nilotinib due to antacid-induced gastric pH increases. Nilotinib's solubility is pH-dependent and it is insoluble at a pH of 4.5 or higher.

MANAGEMENT: Patients treated with nilotinib should not take antacids or other agents with acid-neutralizing effects for at least 2 hours before or 2 hours after a nilotinib dose.

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.