Drug Interaction Report

MONITOR: Theoretically, coadministration with CYP450 3A4 inhibitors may increase the plasma concentrations of topical tacrolimus. The proposed mechanism involves inhibition of CYP450 3A4-mediated metabolism of tacrolimus, which is primary metabolized by this isoenzyme. However, systemic exposure from topical tacrolimus is reported to be minimal (less than 1 ng/mL) and so clinically significant drug interactions are not expected. Nevertheless, the possibility of an interaction cannot be ruled out.

MANAGEMENT: According to the manufacturer, caution is advised if topical tacrolimus is prescribed with CYP450 3A4 inhibitors. Patients should be monitored for systemic tacrolimus adverse effects including immunosuppression, infection, hyperkalemia, malignancy, nephrotoxicity, neurotoxicity, and hypertension.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of crizotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because crizotinib 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.

Food has no significant effect on the gastrointestinal absorption of crizotinib. According to the product labeling, a high-fat meal reduced crizotinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 14%.

MANAGEMENT: Patients treated with crizotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Crizotinib may be taken without regards to food.