Ivacaftor
CFTR modulators
CFTR modulators
The first CFTR potentiator: it opens the chloride channel more often in cystic fibrosis caused by gating variants such as G551D.
Quick facts
- Group
- CFTR modulators
- Target
- CFTR chloride channel (cystic fibrosis transmembrane conductance regulator)
- Used for
- Cystic fibrosis · As the potentiator in combinations
- Key effects
- Headache · Upper respiratory infections
- Monitor
- Liver transaminases before · Mood and sleep
- ATC
- R07AX02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows ivacaftor bound to human CFTR in the membrane (cryo-EM), at a site away from the ATP-binding domains.
Ivacaftor is a CFTR potentiator. In gating variants such as G551D the channel reaches the cell surface but rarely opens. Ivacaftor binds the channel and increases its open probability, so more chloride flows out of epithelial cells, water follows and secretions become thinner. Alone it works only for variants with channels at the surface; for F508del it is combined with correctors that bring the protein to the membrane.
- In gating variants CFTR reaches the membrane but rarely opens
- Ivacaftor binds CFTR and increases its open probability
- Chloride leaves the epithelial cell and water follows
- Airway mucus becomes thinner and easier to clear
Indications
- Cystic fibrosis with at least one gating or other ivacaftor-responsive CFTR variant (for example G551D) Cystic fibrosis →
- As the potentiator in combinations with CFTR correctors for F508del
Adverse effects
Common
- Headache
- Upper respiratory infections and nasal congestion
- Mouth and throat pain
- Abdominal pain, diarrhoea and nausea
- Rash and dizziness
Contraindications
- Hypersensitivity to ivacaftor
- Not recommended with strong CYP3A inducers
- Caution in moderate or severe liver disease
Key interactions
- Strong CYP3A inducers (St John's wort, rifampicin)
- Much lower ivacaftor levels and loss of effect
- CYP3A inhibitors (ketoconazole) and grapefruit
- Higher ivacaftor levels; the regimen is adjusted
What is monitored
- Liver transaminases before and during treatment
- Eye examinations in children before and during treatment
- Mood and sleep
- Lung function and symptoms
Administration and safety
- Oral tablets or granules; the granules are mixed with a small amount of soft food or liquid, and doses are taken with fat-containing food
- Grapefruit and grapefruit juice are avoided
- Used only after genetic testing shows a responsive CFTR variant
Pregnancy and breastfeeding
Human data are limited; use in pregnancy is decided with the cystic fibrosis team, weighing disease control against unknown risks.
Nursing care
- Check that the patient's CFTR genotype has been confirmed
- Review liver test results and teach the signs of liver injury
- Arrange eye checks for children
- Ask about herbal products such as St John's wort and teach that doses go with a fatty meal
Pharmacokinetics
- Absorption
- Oral; taken with fat-containing food
- Metabolism
- Liver, mainly CYP3A
Test yourself
Think of the answer, then tap the question to see it.
What type of CFTR modulator is ivacaftor?
A potentiator: it increases the open probability of CFTR channels already at the cell surface.
Why does ivacaftor alone help little in F508del homozygotes?
F508del protein is destroyed before reaching the membrane; there is little channel for ivacaftor to open, so correctors are added.
Which eye problem is checked for in children on ivacaftor?
Cataracts (lens opacities).
Connections
← Back to the class: CFTR modulators
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Ivacaftor: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 6O2P: Complex of ivacaftor with cystic fibrosis transmembrane conductance regulator (CFTR) (RCSB Protein Data Bank, 2019); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.