Drug Interaction Report

Coadministration with CYP450 3A4 inhibitors is not expected to have clinically significant effects on the plasma concentrations of cabazitaxel, a narrow therapeutic index drug, which is primarily metabolized via the isoenzyme. A drug interaction study in patients with advanced cancers (n=13), revealed repeated administration of the moderate CYP450 3A4 inhibitor aprepitant (125 mg or 80 mg once daily) did not modify the exposure to cabazitaxel (15 mg/m2 intravenous). Clinical data with less potent CYP450 3A4 inhibitors are not available.

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of orally administered ranolazine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ranolazine prolongs QT interval in a dose-dependent manner, high plasma levels of ranolazine may increase the risk of ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsade de pointes.

MANAGEMENT: Patients treated with ranolazine should avoid consumption of grapefruit juice and other grapefruit products if possible. Otherwise, the dosage of ranolazine should be limited to 500 mg twice a day.