Drug Interactions between Alyftrek and sotorasib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation- dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. The risk and/or severity of serious side effects such as liver damage may be increased.

ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation- dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. The risk and/or severity of serious side effects such as liver damage may be increased.

ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation- dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. The risk and/or severity of serious side effects such as liver damage may be increased.

ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.

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.