Drug Interaction Report

MONITOR: Coadministration with miconazole may increase the plasma concentrations of drugs that are substrates of CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by miconazole, which is thought to be a relatively potent inhibitor of the isoenzyme. No formal drug interaction studies have been conducted with miconazole buccal tablets. Although systemic absorption following mucous membrane exposure is limited, the potential for interaction with drugs metabolized by CYP450 3A4 cannot be ruled out.

MANAGEMENT: Caution is advised if miconazole must be used concurrently with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever miconazole is added to or withdrawn from therapy.

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.