Drug Interaction Report

Coadministration with inhibitors of CYP450 2D6 may modestly increase the plasma concentrations of ranolazine, which is partially metabolized by the isoenzyme. When ranolazine 1000 mg twice a day was given to healthy volunteers with the potent CYP450 2D6 inhibitor paroxetine at 20 mg once a day, mean steady-state ranolazine plasma concentrations increased by 1.2-fold. This is not considered clinically significant, and no dosage adjustment of ranolazine is required when used with CYP450 2D6 inhibitors.

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.