Drug Interaction Report

CONTRAINDICATED: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ranolazine, which is primarily metabolized by the isoenzyme. In pharmacokinetic studies, the potent inducer rifampin (600 mg once a day) has been shown to reduce the plasma concentrations of ranolazine (1000 mg twice a day) by approximately 95%. No data are available for other CYP450 3A4 inducers.

MANAGEMENT: The manufacturer considers the use of ranolazine to be contraindicated in patients taking potent CYP450 3A4 inducers such as carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, primidone (partially metabolized to phenobarbital), rifamycins, and St. John's wort. The extent to which other, less potent CYP450 3A4 inducers may interact with ranolazine is unknown. Caution is advised if they are used with ranolazine.

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.

Food does not appear to have a clinically significant effect on the oral bioavailability of sotorasib. When a 960 mg dose of sotorasib was administered to study patients with a high-fat, high-calorie meal (approximately 800 to 1000 calories; 150, 250, and 500 to 600 calories from protein, carbohydrate, and fat, respectively), sotorasib peak plasma concentration (Cmax) did not change while systemic exposure (AUC 0-24 hours) increased by 25% compared to administration under fasted conditions. Sotorasib can be administered with or without food at approximately the same time each day.