Drug Interaction Report

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may decrease the plasma concentrations of eravacycline, which undergoes oxidation by CYP450 3A4 and flavin monooxygenase (FMO). When eravacycline was given with the potent CYP450 3A4 inducer, rifampin, eravacycline systemic exposure (AUC) decreased by 35% and clearance increased by 54%. Reduced therapeutic efficacy of eravacycline may occur.

MANAGEMENT: Eravacycline dosage should be increased to 1.5 mg/kg every 12 hours when used with potent CYP450 3A4 inducers. When a CYP450 3A4 inducer is started, it is important to remember that they exert their effect in a time-dependent manner and may take at least 2 weeks to reach maximal effect. Likewise, when discontinuing a CYP450 3A4 inducer, the induction may take at least 2 weeks to decline. No dosage adjustment is warranted when eravacycline is used with a weak or moderate inducer.

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.