CFTR Triple Modulator (Cystic Fibrosis — F508del) Pregnancy: There are no or limited data (fewer than 300 pregnancy outcomes) in pregnant women; as a precautionary measure it is preferable to avoid use during pregnancy. It is unknown whether the components are excreted in human milk and a risk to the newborn/infant cannot be excluded, so a decision must be made whether to discontinue breast-feeding or therapy (§4.6).

Elexacaftor / Tezacaftor / Ivacaftor

Brand names: Kaftrio (EU/UK), Trikafta (US)

Elexacaftor/tezacaftor/ivacaftor is a CFTR modulator combination used to treat cystic fibrosis in patients with eligible CFTR mutations, including children.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Adults and paediatric patients aged 12 years and older: two ivacaftor 75 mg / tezacaftor 50 mg / elexacaftor 100 mg tablets in the morning, plus one ivacaftor 150 mg tablet in the evening

Route: Oral — swallow the tablets whole (do not chew, crush or break them); take with fat-containing food

Frequency: Twice daily — the morning and evening doses should be taken approximately 12 hours apart, and must not be taken at the same time

Kaftrio should only be prescribed by healthcare professionals with experience in the treatment of CF. If the genotype is unknown, an accurate and validated genotyping method should confirm the presence of at least one F508del mutation. Monitor transaminases (ALT and AST) and total bilirubin in all patients before starting, every 3 months during the first year and annually thereafter (more frequently if there is a history of liver disease or transaminase elevations). PAEDIATRIC DOSING (fixed tablet strengths by age and weight band, not per kg, so paedDose is null): 6 to <12 years and <30 kg — two ivacaftor 37.5 mg / tezacaftor 25 mg / elexacaftor 50 mg tablets in the morning plus one ivacaftor 75 mg tablet in the evening; 6 to <12 years and >=30 kg — the same as the >=12 years regimen (two ivacaftor 75 mg / tezacaftor 50 mg / elexacaftor 100 mg tablets in the morning plus one ivacaftor 150 mg tablet in the evening). Safety and efficacy of Kaftrio in combination with ivacaftor in children aged less than 2 years have not yet been established. MISSED DOSE: if 6 hours or less have passed since a missed morning or evening dose, take it as soon as possible and continue the original schedule; if more than 6 hours have passed since the missed morning dose, take it as soon as possible and do not take the evening dose; if more than 6 hours have passed since the missed evening dose, do not take it — the next scheduled morning dose is taken at the usual time. CYP3A INHIBITORS: with moderate CYP3A inhibitors, alternate each day — two IVA/TEZ/ELX tablets on the first day, one ivacaftor tablet on the next day, with no evening ivacaftor dose; with strong CYP3A inhibitors, two IVA/TEZ/ELX tablets twice a week approximately 3 to 4 days apart, with no evening ivacaftor dose. HEPATIC IMPAIRMENT: mild (Child-Pugh A) no dose adjustment; moderate (Child-Pugh B) use not recommended, and only if there is a clear medical need and benefits outweigh risks, at a reduced dose (Day 1 two IVA/TEZ/ELX tablets in the morning, Day 2 one IVA/TEZ/ELX tablet in the morning, alternating thereafter, with no evening ivacaftor dose); severe (Child-Pugh C) should not be used. No dose adjustment in the elderly. Interactions listed below are those named within §4.2 — the full §4.5 section was not retrieved in this bundle.

Dose adjustments

Renal

No dose adjustment is recommended for patients with mild or moderate renal impairment; there is no experience in patients with severe renal impairment or end-stage renal disease (§4.2)

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance(s) or to any of the excipients (§4.3)

Side effects

Headache (17.3%) — very common
Diarrhoea (12.9%) and abdominal pain — very common
Upper respiratory tract infection (11.9%) and nasopharyngitis — very common
Transaminase elevations / aminotransferase increased (10.9%) — very common; liver injury and total bilirubin elevations reported post-marketing (frequency not known)
Rash — very common; serious adverse reactions of rash were reported in 3 patients (1.5%) on IVA/TEZ/ELX with IVA versus 1 (0.5%) on placebo
Dizziness — very common

Interactions

Moderate CYP3A inhibitors (e.g. fluconazole, erythromycin, verapamil) — reduce the dose to the alternate-day schedule described in §4.2 (two IVA/TEZ/ELX tablets on day 1, one ivacaftor tablet on day 2, no evening ivacaftor dose)
Strong CYP3A inhibitors (e.g. ketoconazole, itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin) — reduce to two IVA/TEZ/ELX tablets twice a week approximately 3 to 4 days apart, with no evening ivacaftor dose
Ciprofloxacin is not expected to have a clinically relevant effect on ivacaftor/tezacaftor/elexacaftor exposure; no dose adjustment is recommended
Food or drink containing grapefruit should be avoided during treatment

Clinical monograph

How it works

Elexacaftor and tezacaftor are correctors that increase the amount of CFTR protein at the cell surface, while ivacaftor is a potentiator that enhances chloride transport through the channel.

Prescribing in practice

It can cause transaminase elevations and liver injury, so liver function must be checked before and during treatment and the drug interrupted if significant derangement occurs.
It is a sensitive substrate of CYP3A, so strong inducers reduce its effect and dosing must be adjusted with strong inhibitors; care is needed with concomitant interacting drugs.
Cases of cataract have been reported in children, so baseline and follow-up ophthalmological examination is recommended in paediatric patients.

Monitoring

Monitor liver function tests before and periodically during treatment, and arrange eye examinations in children.

Counselling the patient

Take the medicine with fat-containing food to help absorption.
Attend your blood tests and eye checks as arranged, and report yellowing of the skin or eyes or abdominal pain.
Tell your team about any new medicines, including over-the-counter and herbal products such as St John's wort.

Evidence & guidelines

Trials of elexacaftor/tezacaftor/ivacaftor demonstrated marked improvements in lung function in eligible patients with cystic fibrosis.

Reference: Heijerman et al. NEJM 2019; Middleton et al. NEJM 2019; NICE TA795; MHRA SPC Kaftrio; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways