The Pharmaceutical Benefits Scheme (PBS) listing for lumacaftor plus ivacaftor (Orkambi®) has recently been expanded to include patients from one year of age. This medicine is indicated for the treatment of cystic fibrosis in patients who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

One of the functions of the CFTR protein is regulation of the flow of chloride ions across the membranes of cells that produce mucus, sweat, saliva, tears, and digestive enzymes. The F508del mutation leads to a reduction in the quantity and functionality of CFTR at the cell surface, resulting in the production of abnormally thick and sticky mucous. In the respiratory tract, accumulation of this dehydrated mucous leads to chronic infection, inflammation, and irreversible lung damage.

It is hoped that initiating treatment in younger patients may slow the progression of organ damage. Rayment et al. (2022) conducted a phase 3 study of lumacaftor plus ivacaftor in one-year-old children with cystic fibrosis. The chloride concentration of sweat was measured as this is a clinical indicator of CFTR function and disease severity. Sweat chloride concentration reduced following four weeks of treatment, which was sustained for the 24-week treatment period (mean reduction of 29.1 mmol/L). While this study did have a small sample size, the observed safety profile was consistent with that seen in larger studies conducted in adolescents and adults. In these larger trials, the most commonly reported adverse effects include dyspnoea, diarrhoea, and nausea.

Orkambi® is available as tablets and granules. The tablets should be swallowed whole, while the granules may be mixed with one teaspoon of age-appropriate soft food or liquid. For optimal absorption, doses should be administered just before or just after the ingestion of fat-containing food.


  1. Hanssens LS, Duchateau J, Casimir GJ. CFTR protein: not just a chloride channel? Cells 2022; 10(11).
  2. Orkambi® (Lumacaftor/ivacaftor) Australian approved product information. St Leonards: Vertex Pharmaceuticals. Approved May 2023.
  3. Rayment JH, Asfour F, Rosenfeld M, Higgins M, Liu L, Mascia M, et al. A phase 3, open-label study of lumacaftor/ivacaftor in children 1 to less than 2 years of age with cystic fibrosis homozygous for F508del-CFTR. Am J Respir Crit Care Med. 2022; 206(10), 1239-1247.

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