Drug Interactions between ivacaftor / lumacaftor and ixazomib

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 may reduce the oral bioavailability of ixazomib. A food effect study found that administration of a single 4 mg dose of ixazomib with a high-fat meal decreased ixazomib peak plasma concentration (Cmax) by 69% and systemic exposure (AUC) by 28%.

MANAGEMENT: Ixazomib should be taken at least one hour before or two hours after eating. On days when both ixazomib and dexamethasone are administered, advise patients to separate dosing times, since dexamethasone should be taken with food while ixazomib should be taken on an empty stomach.