CFTR Potentiator (Cystic Fibrosis — Gating Mutations)
Pregnancy: Use with caution — animal studies show no reproductive toxicity. CF patients reaching reproductive age have improved fertility with effective CFTR therapy; contraception counselling required. Discuss with specialist if pregnancy occurs.
Ivacaftor
Brand names: Kalydeco
Adult dose
Dose: 150 mg every 12 hours (with fat-containing food)
Route: Oral
Frequency: Every 12 hours with fat-containing food
Max: 300 mg/day
CF patients with one or more gating mutations (G551D most common; also G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D, and R117H). Adult and paediatric dosing identical above 6 years. Grapefruit juice significantly increases ivacaftor — avoid. Source: BNF 90; NICE TA170.
Paediatric dose
Dose: 1 month–5 years: 25 mg (under 5 kg) or 50 mg (5–7 kg) or 75 mg (≥7 kg) every 12h. 6–11 years: 150 mg every 12h (same as adult). ≥12 years: 150 mg every 12h mg (age/weight-banded)/kg
Route: Oral (granules for infants, film-coated tablets from 6 years)
Frequency: Every 12 hours with fat-containing food
Max: 150 mg per dose
Licensed from 1 month for gating mutations (G551D and others). Granule formulation for infants mixed with soft food. Critical: must be taken with fat-containing food (avocado, eggs, nuts, full-fat dairy) — fat increases ivacaftor AUC 2–4 fold. Source: BNF for Children 2024; MHRA SPC Kalydeco.
Dose adjustments
Renal
No dose adjustment required.
Hepatic
Moderate hepatic impairment (Child-Pugh B): reduce dose to 150 mg once daily. Severe (Child-Pugh C): use 150 mg once daily or less frequent dosing — specialist decision.
Paediatric weight-based calculator
Licensed from 1 month for gating mutations (G551D and others). Granule formulation for infants mixed with soft food. Critical: must be taken with fat-containing food (avocado, eggs, nuts, full-fat dairy) — fat increases ivacaftor AUC 2–4 fold. Source: BNF for Children 2024; MHRA SPC Kalydeco.
Clinical pearls
- STRIVE trial (NEJM 2011): ivacaftor in G551D mutation carriers aged ≥12 years improved FEV1 by 10.6 percentage points, reduced sweat chloride by 47.9 mmol/L (near-normalisation), and reduced pulmonary exacerbations by 55% — transformative efficacy. The first drug to treat the underlying CFTR dysfunction rather than its symptoms.
- Genotype testing mandatory: ivacaftor ONLY works in patients with CFTR gating mutations (mutations where the CFTR channel is present but does not open). It will not work in F508del/F508del patients (deletion mutation — channel is misfolded/absent) — those patients need triple therapy (KAFTRIO). Always confirm CFTR genotype before prescribing.
- Cataract monitoring in children: cataracts (non-congenital lens opacities) reported in paediatric patients on ivacaftor. Annual ophthalmological examination required — document at every annual review. Mechanism unclear but MHRA requires this monitoring in all patients under 18.
- Fat-containing food is mandatory: fat increases ivacaftor absorption 2–4-fold. 'Half-sandwich' or similar snack acceptable — avocado, eggs, nuts, full-fat dairy, cheese. If patient takes ivacaftor fasted — therapeutic levels not achieved. Counselling at every visit — especially in anorexic CF patients.
- Transformative in eligible mutation carriers: sweat chloride normalisation means CF children with gating mutations treated from infancy may not develop the progressive lung disease that characterises CF. Early treatment, possibly from neonatal diagnosis, is being studied. Source: BNF for Children 2024; Ramsey et al. NEJM 2011 (STRIVE); NICE TA170; MHRA SPC Kalydeco.
Contraindications
- Patients without an applicable CFTR gating or residual function mutation — ivacaftor will not work without a responsive CFTR mutation
- Concurrent strong CYP3A4 inducers (rifampicin — reduces ivacaftor by 89%) — contraindicated
- Severe hepatic impairment (Child-Pugh C) — avoid
Side effects
- Elevated liver transaminases (LFTs) — most important; monthly monitoring initially; can be severe; MHRA warning
- Abdominal pain, diarrhoea, nausea (common)
- Rash, headache, nasopharyngitis
- Cataract — elevated lens opacities reported in paediatric patients; annual ophthalmological exam required
- Elevated creatine kinase (CK) — muscular symptoms; monitor
Interactions
- Strong CYP3A4 inducers (rifampicin, St John's Wort): reduce ivacaftor AUC by 89% — contraindicated
- Strong CYP3A4 inhibitors (clarithromycin, itraconazole, ketoconazole): increase ivacaftor AUC 8–15-fold — reduce ivacaftor dose to 150 mg twice weekly
- Grapefruit juice: increases ivacaftor exposure — avoid throughout treatment
- Moderate CYP3A4 inhibitors (fluconazole, erythromycin): increase ivacaftor — reduce to 150 mg once daily
Monitoring
- Liver function tests (ALT, AST) — monthly for 3 months, then every 3 months for first year, then annually
- Ophthalmological exam (annual — cataract monitoring; mandatory in paediatric patients)
- Lung function (FEV1, FVC) every 3–6 months
- Sweat chloride testing (response marker — expected significant reduction towards normal)
- Body weight and nutritional status (CF nutrition monitoring)
- Pulmonary exacerbation frequency (reduced frequency indicates treatment response)
Reference: BNF for Children 2024; BNF 90; Ramsey et al. NEJM 2011 (STRIVE); NICE TA170; MHRA SPC Kalydeco. Verify against your local formulary and the latest BNF before prescribing.
Related
Curated clinical cross-links plus same-class fallbacks.
Calculators