Ivacaftor

How it works

Potentiates the defective CFTR protein at the cell surface by increasing channel-open probability, enhancing chloride transport in cells expressing responsive CFTR mutations.

Prescribing in practice

• Prescribe only when an eligible responsive CFTR mutation is confirmed, as ivacaftor is ineffective in non-responsive genotypes; specialist CF centre initiation is required.
• It is a CYP3A substrate, so doses are reduced with CYP3A inhibitors and it is generally avoided with strong CYP3A inducers; take with fat-containing food to aid absorption.
• Baseline and periodic liver function tests are required because transaminase elevations occur.

Monitoring

Monitor liver function tests at baseline and periodically, and arrange ophthalmological assessment for cataracts in children as recommended.

Counselling the patient

• Take with fat-containing food to help the medicine be absorbed.
• Avoid grapefruit and Seville oranges, which can raise drug levels.
• Attend liver blood test and eye check appointments and report new abdominal pain or jaundice.

Evidence & guidelines

Ivacaftor for gating-mutation cystic fibrosis is supported by landmark CFTR-modulator trials and NICE technology appraisal guidance, restricted to eligible genotypes.