KALYDECO

What it is

Kalydeco is available as film-coated tablets containing 150 mg of ivacaftor, and as granules in sachets containing 13.4 mg, 25 mg, 50 mg or 75 mg of ivacaftor. Ivacaftor is a selective potentiator of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. In vitro, ivacaftor increases the open probability of the CFTR channel gate to enhance chloride transport, which has been demonstrated in normal CFTR and in mutant forms of CFTR that have reduced channel-open probability, such as G551D-CFTR and R117H-CFTR.

Approved indications —

Cystic fibrosis in patients aged 1 month and older who have at least one mutation in the CFTR gene that is responsive to ivacaftor potentiation.

Dosing overview

Dosing for patients aged 1 month and older is based on age and weight. Infants aged 1 month to less than 2 months weighing greater than 3 kg receive one sachet of 13.4 mg granules every 24 hours. Infants aged 2 months to less than 4 months weighing greater than 3 kg receive one sachet of 13.4 mg granules every 12 hours. Infants aged 4 months to less than 6 months weighing 5 kg or greater receive one sachet of 25 mg granules every 12 hours. Children aged 6 months and older weighing 5 kg to less than 7 kg receive one sachet of 25 mg granules every 12 hours; those weighing 7 kg to less than 14 kg receive one sachet of 50 mg granules every 12 hours; those weighing 14 kg to less than 25 kg receive one sachet of 75 mg granules every 12 hours; and those weighing 25 kg or greater receive one 150 mg tablet every 12 hours. A fat-containing meal or snack should be consumed just before or just after dosing of Kalydeco, with meals and snacks recommended in CF guidelines or standard nutritional guidelines containing adequate amounts of fat. Food containing grapefruit should be avoided during treatment with Kalydeco.

Key safety warnings

Hypersensitivity reactions, including cases of anaphylaxis, have been reported in the post-marketing setting. If signs or symptoms of serious hypersensitivity reactions develop during treatment, Kalydeco should be discontinued and appropriate therapy instituted. Cases of non-congenital lens opacities without impact on vision have been reported in paediatric patients treated with ivacaftor. Although other risk factors were present in some cases, a possible risk attributable to ivacaftor cannot be excluded. Baseline and follow-up ophthalmological examinations are recommended in paediatric patients initiating Kalydeco treatment. Liver function tests are recommended for all patients prior to initiating Kalydeco, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of transaminase elevations, more frequent monitoring of liver function tests should be considered. Dosing should be interrupted in patients with ALT or AST of greater than 5 times the upper limit of normal. Following resolution of transaminase elevations, consideration should be given to the continuation of treatment after assessment of the individual benefits and risks.

Contraindications

Kalydeco should not be used in patients with hypersensitivity to the active substance or to any component of the medicine.

PBS listing

Kalydeco tablets (150 mg) and granules sachets (13.4 mg, 25 mg, 50 mg and 75 mg) are listed on the PBS with authority required restriction. The ex-manufacturer price is A$20,306.25 per listing period.

Regulatory history

The TGA approved Kalydeco on 1 July 2013 for the treatment of cystic fibrosis in patients aged 6 years and older who have a G551D mutation in the CFTR gene, with initial registration on the Australian Register of Therapeutic Goods on 9 July 2013. In November 2014, the PBAC recommended Kalydeco for the treatment of cystic fibrosis in patients aged 6 years and older who have a G551D mutation in the CFTR gene. In November 2015, the PBAC recommended a change to continue access for ivacaftor for specified CF patients aged 6 years and older with G551D or other gating mutations who have severe CF disease (FEV1 <40% predicted). In November 2016, the PBAC recommended a new presentation for patients aged 2 to 5 years with G551D mutation or other class III gating mutations under the Highly Specialised Drugs Program. In November 2017, the PBAC recommended an amendment to expand eligibility criteria to include patients with cystic fibrosis aged 12 months and older who have a G551D mutation or other specified gating mutations. In November 2023, the PBAC recommended extension of the listing to include treatment of CF in patients aged 4 months and older with at least one CFTR gene mutation responsive to ivacaftor. In March 2025, the PBAC recommended a new listing for cystic fibrosis in patients aged 1 to 4 months who have a gating mutation or at least one mutation in the CFTR gene.