Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of sotorasib, which is partially metabolized by the isoenzyme. According to the prescribing information, the main metabolic pathways of sotorasib are non-enzymatic conjugation and oxidative metabolism via CYP450 3A isoenzymes. When a single dose of sotorasib was coadministered with multiple doses of rifampin, a potent CYP450 3A4 inducer, sotorasib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 35% and 51%, respectively. Reduced therapeutic efficacy of sotorasib may occur. No clinically significant effect on sotorasib exposure was observed following coadministration with a single dose of rifampin.

MANAGEMENT: Concomitant use of sotorasib with potent CYP450 3A4 inducers should generally be avoided.

GENERALLY AVOID: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.

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.