ivacaftor + lumacaftor: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
ivacaftor + lumacaftor: clinical details
Prescribing considerations
- Confirm F508del homozygosity using an accurate validated genotype method.
- Initiation should be supervised by a clinician experienced in cystic fibrosis.
- Respiratory reactions and transient FEV1 decline may occur at initiation; consider additional monitoring when baseline lung function is markedly reduced.
- Initiating treatment during a pulmonary exacerbation is not advised.
- Review the full medication list for CYP3A, CYP2B6, CYP2C and transporter-mediated interactions.
- Hormonal contraception may be ineffective during treatment.
- Use caution in advanced liver disease and severe renal impairment; treatment after organ transplantation is not recommended.
Contraindications and cautions
- Hypersensitivity to lumacaftor, ivacaftor or a formulation excipient.
- Not suitable for CF with only one F508del allele and not recommended for CFTR gating mutations.
Monitoring
- Check ALT, AST and bilirubin before treatment, every three months during the first year and annually thereafter; monitor more often with previous abnormalities or liver disease.
- Interrupt treatment and investigate clinically significant transaminase elevation, bilirubin elevation or jaundice.
- Monitor blood pressure periodically.
- Arrange baseline and follow-up ophthalmological examinations for paediatric patients.
- Monitor respiratory status closely during initiation in patients with severely impaired lung function.
Clinical pharmacology
Lumacaftor corrects F508del-CFTR processing and trafficking, while ivacaftor potentiates channel opening. Lumacaftor strongly induces CYP3A; ivacaftor is primarily metabolised by CYP3A. Both are eliminated mainly through the faecal route.
Formulation and product differences
- Film-coated tablets are licensed from age 6 years and must be swallowed whole.
- Granules are licensed from age 1 year, with preparation selected according to age and weight.
- Granules are supplied in single-use sachets for mixing with a small amount of soft food or liquid.
ivacaftor + lumacaftor preparations and strengths
Sachet
Route: Oral
Strengths: 75 mg + 94 mg, 100 mg + 125 mg, 150 mg + 188 mg
Tablet
Route: Oral
Strengths: 100 mg + 125 mg, 200 mg + 125 mg
ivacaftor + lumacaftor interactions
Lumacaftor strongly induces CYP3A and can substantially alter other treatments. Check prescriptions, over-the-counter products and herbal remedies with the CF team or pharmacist.
Hormonal contraceptives
Pills, injections, patches and implants may become less reliable and should not be relied upon as effective contraception during treatment.
Rifampicin, rifabutin or rifapentine
These can lower ivacaftor exposure and reduce treatment effectiveness; combined use is generally not recommended.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.