Drug Interaction Report

GENERALLY AVOID: Coadministration with inhibitors of UGT1A1 may increase the plasma concentrations of belinostat, which is primarily (80% to 90%) metabolized by UGT1A1-mediated glucuronidation.

MANAGEMENT: Concomitant use of belinostat with potent UGT1A1 inhibitors such as atazanavir should generally be avoided. Caution is advised when used with other agents that may also inhibit UGT1A1 such as nilotinib, pazopanib, regorafenib and sorafenib. Patients should be monitored closely for potentially increased adverse effects such as nausea, vomiting, diarrhea, thrombocytopenia, leukopenia (neutropenia and lymphopenia), anemia, infection, and hepatotoxicity.

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.