Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 2D6 and/or 3A4 may increase the plasma concentrations of cevimeline, which is metabolized by these isoenzymes.

MANAGEMENT: Dosage adjustments and clinical monitoring may be appropriate whenever a CYP450 2D6 and/or 3A4 inhibitor is added to or withdrawn from therapy. Patients should be advised to notify their physician if they experience excessive adverse cholinergic effects of cevimeline such as nausea, vomiting, diarrhea, sweating, salivation, urinary frequency, visual disturbance, confusion, tremor, palpitations, or irregular heartbeat.

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.