Drug Interaction Report

ADJUST DOSE: Coadministration with moderate inhibitors of CYP450 3A4 and P-glycoprotein may significantly increase the plasma concentrations of everolimus following oral administration. Everolimus is a substrate of both the CYP450 3A4 isoenzyme and P-glycoprotein drug efflux transporter, thus their inhibition in the intestine can enhance the absorption of everolimus. The risk of side effects such as pneumonitis, stomatitis, infection, dyspnea, diarrhea, anemia, leucopenia, thrombocytopenia, hyperglycemia, and hyperlipidemia may be increased.

MANAGEMENT: Blood trough levels should be closely monitored, and the dosage adjusted accordingly during concomitant administration and after discontinuation of moderate CYP450 3A4 and P-glycoprotein inhibitors. The manufacturer's drug product labeling should be consulted for specific recommendations.

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.

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered everolimus. The mechanism is inhibition of CYP450 3A4 and P-glycoprotein activity in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with everolimus should avoid consumption of grapefruit and grapefruit juice.