ivacaftor, tezacaftor and elexacaftor

R07AX32

Forms & Strengths

Co-packaged tablets: elexacaftor 100 mg / tezacaftor 50 mg / ivacaftor 75 mg and ivacaftor 150 mg
Co-packaged tablets: elexacaftor 50 mg / tezacaftor 25 mg / ivacaftor 37.5 mg and ivacaftor 75 mg
Oral granules: elexacaftor 75 mg / tezacaftor 37.5 mg / ivacaftor 50 mg and ivacaftor 75 mg
Oral granules: elexacaftor 50 mg / tezacaftor 25 mg / ivacaftor 37.5 mg and ivacaftor 75 mg

Adult Dosing

Patients 12 years and older: Two combination tablets (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) in the morning and one ivacaftor 150 mg tablet in the evening, taken approximately 12 hours apart with fat-containing food.

Pediatric Dosing

Ages 6 to 11 years weighing >=30 kg: Two combination tablets (elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg) in the morning and one ivacaftor 150 mg tablet in the evening.
Ages 6 to 11 years weighing <30 kg: Two combination tablets (elexacaftor 50 mg/tezacaftor 25 mg/ivacaftor 37.5 mg) in the morning and one ivacaftor 75 mg tablet in the evening.
Ages 2 to 5 years: Weight-based dosing of oral granules administered every 12 hours with fat-containing food.

Indications

Treatment of cystic fibrosis in patients aged 2 years and older who have at least one F508del mutation in the CFTR gene or another responsive mutation.

Mechanism of Action

Elexacaftor and tezacaftor are CFTR correctors that bind to different sites on the CFTR protein to facilitate cellular processing and trafficking, increasing the amount of protein delivered to the cell surface.
Ivacaftor is a CFTR potentiator that increases the channel open probability (or gating) of the CFTR protein at the cell surface, improving chloride transport.

Contraindications

History of hypersensitivity to elexacaftor, tezacaftor, ivacaftor, or any component of the formulation.
Use with strong CYP3A4 inducers (e.g., rifampin, rifabutin, phenobarbital, carbamazepine, St. John's wort).

Adverse Reactions

Drug Interactions

Strong CYP3A4 inducers (e.g., rifampin) significantly decrease exposure and efficacy; coadministration is contraindicated.
Strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, fluconazole, erythromycin) significantly increase exposure to ivacaftor and tezacaftor; dose reductions are required.
CYP3A4 substrates (e.g., digoxin, midazolam): concomitant use may alter their exposure and require monitoring.
OATP1B1/1B3 substrates (e.g., statins): coadministration may increase concentrations of the substrates.

Curated Content: Needs Vetting Before Put to Clinical Use