Drug Interaction Report

Coadministration with inhibitors of uridine diphosphate glucuronosyltransferase (UGT) 1A1 such as atazanavir, nilotinib, or sorafenib may increase the plasma concentrations of raltegravir, which is primarily metabolized by UGT1A1-mediated glucuronidation. However, concurrent use of atazanavir/ritonavir in clinical trials did not result in meaningful differences in the safety of raltegravir. Based on these data, no dosage adjustment of raltegravir is necessary when used together with atazanavir/ritonavir or other UGT1A1 inhibitors.

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.