Elexacaftor + tezacaftor + ivacaftor
CFTR modulators
CFTR modulators
A triple CFTR modulator: two correctors bring the faulty F508del channel to the cell surface and ivacaftor opens it.
Quick facts
- Group
- CFTR modulators
- Target
- CFTR chloride channel (cystic fibrosis transmembrane conductance regulator)
- Used for
- Cystic fibrosis in patients
- Key effects
- Headache · Upper respiratory infections · Diarrhoea
- Monitor
- Liver tests · Eye examinations before · Mood
- ATC
- R07AX32
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows human F508del CFTR (cryo-EM) with all three drugs bound; the highlighted ligand is elexacaftor, and tezacaftor and ivacaftor sit at their own sites.
The most common cystic fibrosis variant, F508del, makes a misfolded CFTR protein that is destroyed before it reaches the cell membrane. Elexacaftor and tezacaftor are correctors: they bind CFTR at different sites during folding and increase the amount of channel that reaches the surface. Ivacaftor is a potentiator: it raises the probability that the channel at the surface is open. Together they restore part of chloride and water transport, so mucus in the airways and other organs becomes thinner.
- F508del CFTR misfolds and is destroyed before reaching the membrane
- Elexacaftor and tezacaftor help it fold and reach the cell surface
- Ivacaftor holds the channel open more of the time
- Chloride and water flow again and mucus becomes thinner
Indications
- Cystic fibrosis in patients with at least one F508del variant or another responsive CFTR variant Cystic fibrosis →
Adverse effects
Common
- Headache
- Upper respiratory infections, runny or stuffy nose
- Diarrhoea, gas and abdominal pain
- Rash
- Conjunctivitis (pink eye)
Contraindications
- Hypersensitivity to any of its components
- Not recommended with strong CYP3A inducers
- Caution in liver disease
Key interactions
- Strong CYP3A inducers (St John's wort, rifampicin)
- Much lower drug levels and loss of effect
- CYP3A inhibitors (ketoconazole) and grapefruit
- Higher drug levels; the regimen is adjusted
What is monitored
- Liver tests (transaminases, bilirubin) before and during treatment
- Eye examinations before and during treatment in children
- Mood, sleep and signs of depression
- Lung function and symptoms
Administration and safety
- Oral tablets or granules; taken with food that contains fat
- Grapefruit and grapefruit juice are avoided
- Prescribed only after the patient's CFTR genotype is known
Pregnancy and breastfeeding
Human data are limited; the decision weighs the benefit of controlling cystic fibrosis against unknown risks, with the specialist team.
Nursing care
- Check liver test results and teach the signs of liver injury: jaundice, dark urine, right upper abdominal pain
- Ask about mood changes and sleep at each visit
- Review the medication list for rifampicin, other enzyme inducers and herbal products such as St John's wort
- Teach that it is taken with a fat-containing meal or snack
Pharmacokinetics
- Absorption
- Oral; taken with fat-containing food
- Metabolism
- Liver, by CYP3A enzymes (grapefruit raises and St John's wort lowers its levels)
Test yourself
Think of the answer, then tap the question to see it.
Which components of the triple combination are correctors and which is a potentiator?
Elexacaftor and tezacaftor are correctors; ivacaftor is the potentiator.
Which CFTR variant is the main target of the triple combination?
F508del, the most common cystic fibrosis variant (one copy is enough).
Which serious adverse effect requires liver tests during treatment?
Drug-induced liver injury, which can be life-threatening.
Why does rifampicin make this treatment fail?
It strongly induces CYP3A and lowers the drug levels.
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: Elexacaftor, Tezacaftor, and Ivacaftor: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); CFTR gene: MedlinePlus Genetics (MedlinePlus (U.S. National Library of Medicine), 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.