Cystic Fibrosis with G551D Mutation (in At Least One of Their CFTR Genes) (see Cystic Fibrosis, [[Cystic Fibrosis]])

  • General Information: FDA-Approved for this Indication in 2012
    • G551D Mutation Occurs in Only 4.4% of CF Patients
    • G551D is a “Gating Mutation”: this mutation impairs the regulated opening of the ion channel that is formed by the CFTR protein
    • Ivacaftor is Indicated for CF Patients > 2 y/o
    • Ivacaftor is the First Approved CF Therapy that Attempts to Restore the Function of a Mutant CF Protein
  • Clinical Efficacy
    • VX08-770-102 Study Group (NEJM, 2011) [MEDLINE]
      • Ivacaftor improved lung function (FEV1) at 2 wks, which was sustained through 48 wks
      • Ivacaftor improved pulmonary exacerbations: 55% risk reduction
      • Ivacaftor improved patient-reported respiratory symptoms, weight, and sweat chloride concentrations
      • Ivacaftor decreased serious adverse events

Cystic Fibrosis with Other CFTR “Gating Mutations” (see Cystic Fibrosis, [[Cystic Fibrosis]])

  • General Information: FDA-Approved for These Mutants
  • Other “Gating Mutations”: G1244E, G1349D, G178R, G551S, R117H, S1251N, S1255P, S549N, S549R


  • CFTR Corrector: restores function of the mutant ion channel in CF patients with “gating mutations”


  • Hepatic


  • PO: 150 mg q12hrs (age 6+)
    • Administer with Fat-Containing Foods

Monitor Liver Function Tests (LFT’s)

  • Check LFT’s Prior to Ivacaftor Administration
  • Check LFT’s q3 mo x 1 yr
  • Check LFT’s Annually Thereafter

Dose Adjustment

  • Hepatic: dose reduce for patients with hepatic impairment
  • Renal: none

Drug Interactions

  • P4503A (CYP3A)-Inhibitors (itraconazole, clarithromycin, fluconazole): it is recommended to dose-reduce ivacaftor, since these agents may increase ivacaftor concentration
  • P4503A (CYP3A)-Inducers (rifampin, phenobarbital, carbamazepine, phenytoin, St. John’s wort): use of ivacaftor with these agents is contraindicated, since these agents significantly decrease ivacaftor concentration

Adverse Effects

Gastrointestinal Adverse Effects

  • Elevated Liver Function Tests (LFT’s)

Ophthlamologic Adverse Effects

  • Cataracts (see Cataracts, [[Cataracts]]): reported in pediatric patients up to 12 y/o


  • Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med 2010;363(21):1991-2003 [MEDLINE]
  • A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011;365(18):1663-1672 [MEDLINE]
  • Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med. 2013 Jun;187(11):1219-25 [MEDLINE]
  • Long-term safety and efficacy of ivacaftor in patients with cystic fibrosis who have the Gly551Asp-CFTR mutation: a phase 3, open-label extension study (PERSIST). Lancet Respir Med. 2014 Nov;2(11):902-10. Epub 2014 Oct 9 [MEDLINE]
  • Clinical mechanism of the cystic fibrosis transmembrane conductance regulator potentiator ivacaftor in G551D-mediated cystic fibrosis. Am J Respir Crit Care Med. 2014 Jul 15;190(2):175-84. doi: 10.1164/rccm.201404-0703OC [MEDLINE]