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. Atazanavir, a UGT1A1 inhibitor, decreased the peak plasma concentration (Cmax) of belinostat by 33% but increased systemic exposure (AUC) by 1.4-fold.

MANAGEMENT: Concomitant use of belinostat with UGT1A1 inhibitors should generally be avoided. If concomitant use of a UGT1A1 inhibitor is unavoidable, the manufacturer recommends that the dosage of belinostat be decreased by 25%; 1,000 mg/m2 dose modified to 750 mg/m2, 750 mg/m2 dose modified to 562.5 mg/m2, and 500 mg/m2 dose discontinued for the duration of UGT1A1 inhibitor use and restarted at the previous dose after five half-lives of the UGT1A1 inhibitor. Patients should be monitored closely for potentially increased adverse effects of belinostat 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.