Drug Interactions between Incivek and lemborexant

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lemborexant, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. When coadministered with itraconazole, a potent CYP450 3A4 inhibitor, lemborexant peak plasma concentration (Cmax) and systemic exposure (AUC) increased approximately 1.4-fold and 3.8-fold, respectively. When coadministered with fluconazole, a moderate CYP450 3A4 inhibitor, lemborexant Cmax and AUC increased approximately 1.6-fold and 4.2-fold, respectively. 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. Increased exposure to lemborexant may increase the risk of adverse reactions such as central nervous system (CNS) depression, sleep paralysis, hallucinations, complex sleep behaviors, worsening of depression or suicidal ideation, nightmares, palpitations, or headache.

After administration of a high-fat, high-calorie meal (approximately 1000 calories with 500 to 600 calories from fat), lemborexant Cmax decreased by 23%, AUC increased by 18%, and the time to maximum concentration (Tmax) was delayed by 2 hours.

MANAGEMENT: The manufacturer makes no recommendation regarding administration with food; however, the time to sleep onset may be delayed if taken with or soon after a meal. Patients should avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with lemborexant.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of telaprevir. When given with a meal containing 533 kcal and 21 g fat, telaprevir systemic exposure (AUC) increased by 237% compared to administration under fasting conditions. The type of meal also affects the exposure to telaprevir. Relative to fasting, telaprevir AUC increased by approximately 117% with a low-fat meal (249 kcal; 3.6 g fat) and 330% with a high-fat meal (928 kcal; 56 g fat). In Phase 3 clinical trials, telaprevir doses were administered within 30 minutes of completing a meal or snack containing approximately 20 grams of fat.

MANAGEMENT: Telaprevir should be administered with food containing approximately 20 grams of fat. Patients should be advised that the fat content of the meal or snack is critical to the absorption of telaprevir. Food taken with telaprevir should be ingested within 30 minutes prior to each dose. Examples of some foods that could be taken with telaprevir include: bagel with cream cheese; half cup of nuts; 3 tablespoons of peanut butter; 1 cup of ice cream; 2 ounces of American or cheddar cheese; 2 ounces of potato chips; or half cup of trail mix.