Published: 3 September 2026
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Spotlight on cystic fibrosis transmembrane conductance regulator (CFTR) modulators
Published: 3 September 2026
Prescriber Update 47(3): 38–40
September 2026
This article gives an overview of CFTR modulator medicines, including key safety considerations. Table 1 provides a list of approved CFTR modulators.
Table 1: CFTR modulators approved in New Zealand
| Brand name | Active substance(s) |
|---|---|
| Trikafta | elexacaftor + tezacaftor +ivacaftor |
| Alyftrek | vanzacaftor + tezacaftor + deutivacaftor |
| Kalydeco | ivacaftor |
| Orkambi | lumacaftor + ivacaftor |
| Symdeko | tezacaftor + ivacaftor |
Source: Medsafe Product/Application Search. URL: www.medsafe.govt.nz/DbSearch/ (accessed 29 July 2026).
How do CFTR modulators work?1
Cystic fibrosis is caused by mutations affecting the CFTR protein, a chloride and bicarbonate ion channel located on epithelial cells. Disrupted ion transport at epithelial surfaces leads to thickened mucus in the lungs and other organs. This means that people with cystic fibrosis experience recurrent respiratory tract infections and decline in lung function, among many other complications.
CFTR modulators work by targeting the faulty CFTR protein to improve lung function. There are two types of CFTR medicines: potentiators and correctors.
Potentiators (eg, ivacaftor, deutivacaftor) improve the function of CFTR protein present at the cell membrane by increasing the probability that the ion channel is open. Correctors (eg, tezacaftor, lumacaftor, elexacaftor, vanzacaftor) increase the number of CFTR proteins on the cell surface by facilitating folding and trafficking of the CFTR protein.
Potentiators and correctors are often used in combination to treat cystic fibrosis, depending on the type of CFTR variant the person has.
Safety considerations2–6
This section describes some significant safety considerations associated with CFTR modulators. Refer to the medicine data sheets for full prescribing information.
Use in hepatic impairment
Because CFTR modulators undergo hepatic metabolism, they are not recommended for use in patients with severe hepatic impairment, and dose reductions are recommended for patients with moderate hepatic impairment.
Elevated transaminases and liver injury
Elevated liver transaminases are common in people with cystic fibrosis and have been observed in people taking CFTR modulators. In some cases, total bilirubin can also be elevated.
Cases of liver failure requiring transplantation have been reported in patients taking elexacaftor + tezacaftor + ivacaftor (Trikafta). These events were seen during the first 6 months of treatment in patients with and without pre-existing advanced liver disease.
Monitor transaminases and total bilirubin throughout CFTR modulator treatment. Interrupt treatment if significant elevations occur or there are clinical signs of liver injury. Following resolution, review the benefits and risks of resuming treatment. Refer to the individual medicine data sheets for further details on liver monitoring.
Mood disturbances
Effects on mood and behaviour such as anxiety, low mood, sleep disturbance and forgetfulness have occasionally been reported in people treated with CFTR modulators. In some young children (aged 2-5 years), these effects may present as behaviour changes.
A causal relationship has not been established with CFTR modulator treatment, and some patients have been reported to recover with continued treatment. Advise patients and caregivers to monitor for new or worsening symptoms and seek medical advice if they occur.
Cataracts
There have been cases of non-congenital lens opacities without impact on vision in paediatric patients treated with ivacaftor-containing regimens. Cataracts were seen in juvenile rat studies with ivacaftor.
Baseline and follow-up ophthalmological examinations are recommended in paediatric patients starting CFTR modulator treatment.
Medicine interactions
Several CFTR modulators are CYP3A substrates, including elexacaftor, tezacaftor, ivacaftor, vanzacaftor and deutivacaftor.
- CYP3A inducers (eg, rifampicin, phenobarbital, carbamazepine, phenytoin) may reduce systemic exposure and decrease the efficacy of these CFTR modulators. Avoid concomitant use of these CFTR modulators with strong CYP3A inducers.
- CYP3A inhibitors (eg, clarithromycin, fluconazole, itraconazole, posaconazole, erythromycin, verapamil) may increase exposure to these CFTR modulators. Reduce the dose of the CFTR modulator if used with moderate or strong CYP3A inhibitors.
Lumacaftor is a strong inducer of CYP3A and may decrease systemic exposure of medicines that are substrates of CYP3A, such as hormonal contraceptives.
Refer to the medicine data sheets for further information on medicine interactions.
New Zealand case reports
Between 1 January 2020 and 31 May 2026, the New Zealand Pharmacovigilance Database received 17 case reports associated with CFTR modulators. These included:
- 5 reports for liver-related adverse events with elexacaftor + tezacaftor + ivacaftor (Trikafta)
- 5 reports describing mood or behaviour changes, of which, 4 reports were associated with elexacaftor + tezacaftor + ivacaftor (Trikafta) and 1 was associated with ivacaftor (Kalydeco).
References
- Ong T and Ramsey BW. 2023. Cystic fibrosis: A review. JAMA 329(21): 1859-71. DOI: 10.1001/jama.2023.8120 (accessed 7 July 2026).
- Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. 2026. Symdeko New Zealand Data Sheet 4 May 2026. URL: www.medsafe.govt.nz/profs/Datasheet/s/symdekotab.pdf (accessed 7 July 2026).
- Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. 2026. Orkambi New Zealand Data Sheet 4 May 2026. URL: www.medsafe.govt.nz/profs/Datasheet/o/orkambitabgranules.pdf (accessed 7 July 2026).
- Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. 2026. Kalydeco New Zealand Data Sheet 4 May 2026. URL: www.medsafe.govt.nz/profs/Datasheet/k/Kalydecotab.pdf (accessed 7 July 2026).
- Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. 2026. Trikafta New Zealand Data Sheet 2 June 2026. URL: www.medsafe.govt.nz/profs/Datasheet/t/trikaftatab.pdf (accessed 7 July 2026).
- Pharmacy Retailing (NZ) Ltd t/a Healthcare Logistics. 2026. Alyftrek New Zealand Data Sheet 4 May 2026. URL: www.medsafe.govt.nz/profs/Datasheet/a/Alyftrektab.pdf (accessed 7 July 2026).
