Drug Interaction Report

ADJUST DOSING INTERVAL: The safety and efficacy of hematopoietic growth factors such as colony-stimulating factors (G-CSF and GM-CSF) and stem cell factors (SCF) given simultaneously with cancer chemotherapy have not been established. Theoretical concerns exist regarding their concomitant administration because hematopoietic growth factors stimulate myeloid cell proliferation while antineoplastic agents primarily target rapidly dividing cells.

MANAGEMENT: Because of the potential sensitivity of rapidly dividing myeloid cells to cancer chemotherapy, hematopoietic growth factors should not be used within 24 hours before or 24 hours after administration of antineoplastic agents.

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.