Drug Interaction Report

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ivacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Elexacaftor and tezacaftor are also CYP450 3A4 substrates in vitro and may interact similarly with grapefruit juice, whereas lumacaftor is not expected to interact.

ADJUST DOSING INTERVAL: According to prescribing information, systemic exposure to ivacaftor increased approximately 2.5- to 4-fold, systemic exposure to elexacaftor increased approximately 1.9- to 2.5-fold, and systemic exposure to lumacaftor increased approximately 2-fold following administration with fat-containing foods relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.

MANAGEMENT: Patients treated with ivacaftor-containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit or Seville oranges. All ivacaftor-containing medications should be administered with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products. A typical cystic fibrosis diet will satisfy this requirement.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailabilities of both elvitegravir and tenofovir. When a single dose of cobicistat/elvitegravir/emtricitabine/tenofovir (trade name Stribild) was given with a light meal (approximately 373 kcal; 20% fat), mean elvitegravir and tenofovir systemic exposures (AUCs) increased by 34% and 24%, respectively, relative to fasting conditions. When administered with a high-fat meal (approximately 800 kcal; 50% fat), the mean AUC of elvitegravir and tenofovir increased by 87% and 23%, respectively, relative to fasting conditions. The alterations in mean AUCs of cobicistat and emtricitabine were not clinically significant with either the light or high-fat meal.

MANAGEMENT: Cobicistat/elvitegravir/emtricitabine/tenofovir as a fixed-dose preparation should be administered once daily with food. Elvitegravir as a single-ingredient preparation should also be administered once daily with food.