From the 1st October 2018, lumacaftor and ivacaftor (Orkambi®) became available on the Pharmaceutical Benefits Scheme (PBS). This combination tablet is approved for use in patients over six years of age who are homozygous for the most common cystic fibrosis transmembrane conductance regulator (CFTR) mutation, F508del. This is a significant listing as lumacaftor-ivacaftor is the first medication to treat the underlying cause of cystic fibrosis in this population.

The CFTR protein is an ion channel located on the surface of epithelial cells in many organs. It functions to move chloride ions out of cells with water following via osmosis. Defects in this protein can reduce chloride transport, leading to dehydration and thickening of mucus including respiratory secretions. This significantly impairs the ability of cilia to clear the airways and results in symptoms such as a persistent cough and breathlessness as well as frequent lung infections.

Lumacaftor is a CFTR corrector that increases the quantity of functional CFTR on the cell surface. Ivacaftor, also available as a single ingredient medication (Kalydeco®), is a CFTR potentiator. It is thought to enhance chloride transport by increasing the open probability of the CFTR channel. Clinical trials demonstrate that ivacaftor alone is not effective for the treatment of patients who are homozygous for the F508del mutation.

Two trials studying the efficacy of lumacaftor-ivacaftor demonstrate a 4.3-6.7% increase in mean relative forced expiratory volume in one second (FEV1) compared to placebo. The rate of pulmonary exacerbations was up to 39% lower in the lumacaftor-ivacaftor group. The PROGRESS extension study demonstrates that improvements in exacerbation rates continue with longer-term therapy.

Lumacaftor is a strong inducer of the hepatic CYP3A enzymes while ivacaftor is a substrate of CYP3A4 and CYP3A5. Therefore, caution must be exercised if co-administered with other substrates or strong inducers of CYP3A.


  1. Orkambi® (lumacaftor and ivacaftor) Australian approved product information. St Leonards: Vertex Pharmaceuticals. Approved August 2018.
  2. Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, et al. Lumacaftor–ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med. 2015; 373: 220-31.

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