Drug Interactions between Crixivan and sotorasib

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).

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.