TRIKAFTA

What it is

TRIKAFTA is a combination medicine containing elexacaftor 100 mg, tezacaftor 50 mg and ivacaftor 75 mg in a morning dose film-coated tablet, with an evening dose film-coated tablet containing ivacaftor 150 mg. A lower-strength formulation contains elexacaftor 50 mg, tezacaftor 25 mg and ivacaftor 37.5 mg in the morning tablet, with an evening tablet containing ivacaftor 75 mg. Granule formulations are also available in two strengths for patients unable to take tablets. Elexacaftor and tezacaftor are CFTR correctors that facilitate the processing and trafficking of mutant CFTR protein to the cell surface, while ivacaftor potentiates the channel opening of CFTR protein, resulting in increased quantity and function of CFTR at the cell surface.

Approved indications

— Treatment of cystic fibrosis in patients aged 2 years and older who have at least one mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that is responsive based on clinical or in vitro evidence.

Dosing overview

Dosing is based on age and weight, ranging from elexacaftor 80 mg/tezacaftor 40 mg/ivacaftor 60 mg granules in the morning for children aged 2 to less than 6 years weighing less than 14 kg, to elexacaftor 100 mg/tezacaftor 50 mg/ivacaftor 75 mg tablets in the morning for patients aged 12 years and older. Morning and evening doses should be taken with fat-containing food, approximately 12 hours apart. A fat-containing meal or snack should be consumed just before or just after dosing, with meals recommended in cystic fibrosis guidelines containing adequate amounts of fat.

Key safety warnings

Cases of liver failure leading to transplantation have been reported within the first 6 months of treatment in patients with and without pre-existing advanced liver disease, and elevated transaminases are common in patients with cystic fibrosis treated with TRIKAFTA, sometimes associated with concomitant elevations in total bilirubin. Assessments of transaminases (ALT and AST) and total bilirubin are recommended for all patients prior to initiating TRIKAFTA, every month during the first 6 months of treatment, every 3 months during the next 6 months and annually thereafter, with more frequent monitoring considered for patients with a history of liver disease or transaminase elevations. TRIKAFTA dosing should be interrupted in the event of ALT or AST greater than 5 times the upper limit of normal, or ALT or AST greater than 3 times the upper limit of normal with total bilirubin greater than 2 times the upper limit of normal. Hypersensitivity reactions, including cases of angioedema and anaphylaxis, have been reported in the post-marketing setting, and TRIKAFTA should be discontinued if signs or symptoms of serious hypersensitivity reactions develop during treatment. Cases of non-congenital lens opacities without impact on vision have been reported in paediatric patients treated with ivacaftor-containing regimens, and although other risk factors were present in some cases, a possible risk attributable to treatment cannot be excluded; baseline and follow-up ophthalmological examinations are recommended in paediatric patients initiating treatment with TRIKAFTA.

Contraindications

TRIKAFTA should not be used in cases of hypersensitivity to the active substances or to any component of this medication.

PBS listing

As of March 2025, TRIKAFTA is recommended for listing on the PBS for cystic fibrosis in patients aged 2 years or older who have at least one mutation in the CFTR gene responsive to TRIKAFTA.

Regulatory history

TRIKAFTA 100/50/75 film-coated tablets were first registered on the ARTG on 24 March 2021. The 50/25/37.5 film-coated tablet formulation was added to the ARTG on 1 November 2022, followed by both granule formulations (100/50/75 and 80/40/60) on 7 February 2024. The PBAC initially deferred a recommendation in March 2021, then again deferred in May 2021. In July 2021, the PBAC recommended TRIKAFTA for the F/MF (F508del/minimal function) population while deferring for a broader population; in December 2021, the PBAC recommended it for patients aged 12 years and older with at least one F508del mutation. The recommendation was extended to patients aged 6 to 11 years with at least one F508del mutation in November 2022 (revised in March 2023), then to patients aged 2 to 5 years with at least one F508del mutation in March 2024. In March 2025, the PBAC recommended TRIKAFTA for patients aged 2 years or older with any CFTR gene mutation responsive to the medicine.