A safety evaluation of ivacaftor for the treatment of cystic fibrosis

Expert Opin Drug Saf. 2016 May;15(5):709-15. doi: 10.1517/14740338.2016.1165666. Epub 2016 Apr 7.


Introduction: Ivacaftor is indicated for treatment of cystic fibrosis (CF) mediated by 10 mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene that causes gating or partial function abnormalities. In placebo-controlled and open-label studies, ivacaftor-treated subjects showed improved pulmonary function, nutrition and quality of life measures. This article reviews ivacaftor safety.

Areas covered: Safety findings in ivacaftor clinical trials, and reported subsequently, were accessed by a PubMed search using key words "VX-770" or "ivacaftor". Additional information was accessed via Google Search. Transaminitis was noted in ivacaftor and combination lumacaftor-ivacaftor trials. Ivacaftor was associated with cataracts in juvenile rat pups in pre-clinical studies; non-congenital cataracts have been found in children taking ivacaftor. Ivacaftor is a CYP3A substrate; CYP3A inhibitors and inducers should be avoided during its administration. Ivacaftor and its M1 metabolite may inhibit CYP3A and P-gp; therefore, ivacaftor may increase systemic exposure to drugs which are substrates of CYP3A and/or P-gp, increasing the potential for adverse events.

Expert opinion: Ivacaftor therapy may be associated with ocular and hepatic side effects; specific recommendations for monitoring are available. Potential drug interactions should be evaluated in patients taking ivacaftor. High clinical efficacy suggests that the risk benefit ratio of ivacaftor favors therapy.

Keywords: Cystic fibrosis; cataract; ivacaftor; transaminitis.

Publication types

  • Review

MeSH terms

  • Aminophenols / adverse effects
  • Aminophenols / therapeutic use*
  • Animals
  • Child
  • Chloride Channel Agonists / adverse effects
  • Chloride Channel Agonists / therapeutic use
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Drug Interactions
  • Humans
  • Mutation
  • Quality of Life
  • Quinolones / adverse effects
  • Quinolones / therapeutic use*
  • Rats


  • Aminophenols
  • Chloride Channel Agonists
  • Quinolones
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor