Elexacaftor / Tezacaftor / Ivacaftor

How it works

Elexacaftor and tezacaftor are correctors that improve the processing and trafficking of CFTR protein to the cell surface, while ivacaftor is a potentiator that increases the channel's open probability. Together they enhance chloride transport across the epithelium.

Prescribing in practice

• Liver enzyme rises and rare serious liver injury can occur, so liver function must be checked before and periodically during treatment, with caution and dose modification in significant hepatic impairment.
• It is metabolised via CYP3A, so concomitant strong CYP3A inducers are contraindicated and inhibitors require dose adjustment.
• Cataracts have been reported in children, and baseline and follow-up eye examinations are advised in paediatric patients.

Monitoring

Monitor liver function tests at baseline and during treatment, and arrange ophthalmological assessment for children.

Counselling the patient

• Take the morning and evening tablets with fat-containing food.
• Report yellowing of the skin or eyes, dark urine, or abdominal pain.
• Avoid grapefruit and tell your team about new medicines, including some antifungals and antibiotics.

Evidence & guidelines

NICE recommends elexacaftor/tezacaftor/ivacaftor for eligible cystic fibrosis genotypes, supported by trials showing improved lung function and reduced exacerbations.