From 1 April 2022, a new treatment for cystic fibrosis was listed on the Pharmaceutical Benefits Scheme (PBS). Trikafta® (elexacaftor, tezacaftor + ivacaftor) is an authority required item supplied under the Section 100 Highly Specialised Drugs program.

Trikafta® is indicated for the treatment of cystic fibrosis in patients 12 years of age and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This is the most common cystic fibrosis mutation and involves the removal of a single amino acid from the CFTR protein.

Mutations of the CFTR gene can affect the production, structure, or stability of the CFTR protein. This protein acts as an ion channel across the membranes of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. It helps regulate the flow of chloride ions, which contributes to the maintenance of water in tissues. While there are many types of mutations that can affect disease severity, the common feature of cystic fibrosis is the production of mucous that is abnormally thick and sticky. This has effects throughout the body, including the respiratory, digestive, and reproductive systems. In the lungs, accumulation of this dehydrated mucous leads to chronic infection, inflammation, and fibrosis.

CFTR modulators

The three medications contained in Trikafta® are known as CFTR modulators. There are two main types of CFTR modulators: correctors and potentiators. Correctors help stabilise the defective CFTR protein, allowing it to form the correct three-dimensional shape. This increases CFTR availability by reducing the premature degradation of defective CFTR. On the other hand, potentiators restore channel activity. There is also a third type of modulator currently undergoing clinical trials. These are known as CFTR amplifiers and act to increase the amount of CFTR protein produced.


Elexacaftor and tezacaftor are CFTR correctors. These two agents bind to different sites on the CFTR protein and have demonstrated additive effects. Ivacaftor is a CFTR potentiator that increases the open probability of the CFTR channel gate. This enhances the transport of chloride ions across cell membranes.

The VX17-445-102 Study investigated the safety and efficacy of Trikafta® over 24 weeks. This double-blind, placebo-controlled trial had a primary endpoint of absolute change from baseline in the percentage of predicted forced expiratory volume in 1 second (FEV1) at week four. Treatment with elexacaftor, tezacaftor, and ivacaftor resulted in a significant improvement in this endpoint, with a mean treatment difference of 13.8 points compared to placebo. This improvement was sustained throughout the trial, with a mean treatment difference of 14.3 points seen at week 24. The annualised rate of pulmonary exacerbations was 63% lower in the treatment group compared to placebo. The majority of patients reported at least one adverse effect (93% of the treatment group and 96% of the placebo group). Adverse effects were typically mild or moderate and led to discontinuation in only 1% of patients in the treatment group (one case of rash and one case of portal hypertension in a patient with pre-existing cirrhosis).


Trikafta® is supplied as a composite pack. The tablets marked as the morning dose contain 100mg of elexacaftor, 50mg of tezacaftor and 75mg of ivacaftor; the evening dose tablets contain only 150mg of ivacaftor.

The usual recommended dose is two tablets in the morning and one tablet in the evening. The tablets should be swallowed whole with a fat-containing meal or snack. Dose adjustments may be required in the event of moderate hepatic impairment or co-administration with strong or moderate CYP3A inhibitors.


Trikafta® has several significant interactions, and patients should be encouraged to check with their healthcare professional before starting any new medication.

Elexacaftor, tezacaftor and ivacaftor are metabolised by CYP3A. Co-administration with strong inducers of CYP3A (e.g. rifampicin, carbamazepine, St John’s wort) is not recommended as efficacy may be significantly reduced. Conversely, exposure is increased when co-administered with inhibitors of CYP3A. The product information provides recommendations for reduced doses when Trikafta® is co-administered with strong or moderate inhibitors of CYP3A (e.g. clarithromycin, erythromycin, verapamil, fluconazole).

Food and drinks containing grapefruit should be avoided during treatment as they may increase the exposure to elexacaftor, tezacaftor and ivacaftor.

Adverse effects:

Common adverse effects associated with Trikafta® include increased creatinine kinase, increased blood pressure, and rash. Non-congenital cataracts have been reported in children and adolescents taking ivacaftor-containing regimens. Although causality has not been confirmed, the product information recommends baseline and follow-up ophthalmological examinations in paediatric patients initiated with Trikafta®.

Being a new medication, Trikafta® is included in the Black Triangle Scheme; practitioners and patients are encouraged to report suspected adverse events to the Therapeutic Goods Administration (TGA).

Other CFTR modulators:

Other CFTR modulator therapies available for the management of cystic fibrosis include:

  • Ivacaftor (Kalydeco®);
  • Lumacaftor + ivacaftor (Orkambi®); and
  • Tezacaftor + ivacaftor (Symdeko®).

The choice of agent is dependent upon the CFTR mutation present.


  1. Middleton PG, Mall MA, Dřevínek P, Lands LC, McKone EF, Polineni D, et al. Elexacaftor–tezacaftor–ivacaftor for cystic fibrosis with a single phe508del allele. N Engl J Med. 2019; 381: 1809-19.
  2. Respiratory Expert Group. Therapeutic Guidelines: Respiratory. Melbourne: Therapeutic Guidelines; 2020.
  3. Ridley K, Condren M. Elexacaftor-tezacaftor-ivacaftor: the first triple-combination cystic fibrosis transmembrane conductance regulator modulating therapy. J Pediatr Pharmacol Ther. 2020; 25(3): 192-7.
  4. Shaughnessy CA, Zeitlin PL, Bratcher PE. Elexacaftor is a CFTR potentiator and acts synergistically with ivacaftor during acute and chronic treatment. Scientific Reports 2021; 11: 19810.
  5. Trikafta® (elexacaftor/tezacaftor/ivacaftor) Australian approved product information. St Leonards: Vertex Pharmaceuticals. Approved September 2021.

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