The safety of lumacaftor and ivacaftor for the treatment of cystic fibrosis

Expert Opinion on Drug Safety

Volumn 16, Issue 11, 2017, Pages 1305-1311

  Talamo Guevara, Maria ^a   McColley, Susanna A ^a,b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b ANN ROBERT H LURIE CHILDREN S HOSPITAL OF CHICAGO   (United States)

Author keywords

cataract; Cystic fibrosis; ivacaftor; lumacaftor; transaminitis

Indexed keywords

CREATINE KINASE; CYTOCHROME P450 3A; IVACAFTOR; LUMACAFTOR; 1,3 BENZODIOXOLE DERIVATIVE; AMINOPHENOL DERIVATIVE; AMINOPYRIDINE DERIVATIVE; CHLORIDE CHANNEL STIMULATING AGENT; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DRUG COMBINATION; LUMACAFTOR, IVACAFTOR DRUG COMBINATION; QUINOLONE DERIVATIVE;

BRONCHOSPASM; CATARACT; CHEST TIGHTNESS; CLINICAL TRIAL; COUGHING; CYSTIC FIBROSIS; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DYSPNEA; HEMOPTYSIS; HUMAN; HYPERTRANSAMINASEMIA; PHARMACODYNAMICS; PHARMACOKINETIC PARAMETERS; POSTMARKETING SURVEILLANCE; RASH; REVIEW; SIDE EFFECT; THERAPY EFFECT; THORAX PAIN; ANIMAL; CHILD; DRUG COMBINATION; DRUG EFFECTS; DRUG INTERACTION; GENETICS; METABOLISM; MUTATION; PATHOPHYSIOLOGY;

AMINOPHENOLS; AMINOPYRIDINES; ANIMALS; BENZODIOXOLES; CHILD; CHLORIDE CHANNEL AGONISTS; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; CYTOCHROME P-450 CYP3A; DRUG COMBINATIONS; DRUG INTERACTIONS; HUMANS; MUTATION; QUINOLONES;

EID: 85029696229     PISSN: 14740338     EISSN: 1744764X     Source Type: Journal    
DOI: 10.1080/14740338.2017.1372419     Document Type: Review

References (30)

1. Ikuma M, Weslh M., Regulation of CFTR Cl- channel gating by ATP binding and hydrolysis. Proc Natl Acad. 2000;97:8675–8680.​​
2. Rowe SM, Miller S, Sorscher EJ., Cystic fibrosis. N Engl J Med. 2005;352:1992–2001.
3. A clinician’s guide to cystic fibrosis. CFTR Sci. [cited 2017 Aug 6]. Available from: https://www.cftrscience.com/?q=epidemiology​​
4. Cystic Fibrosis Foundation Patient Data Registry Report. [cited 2017 Aug 6]. Avaialble from: https://www.cff.org/Our-Research/CF-Patient-Registry/2015-Patient-Registry-Annual-Data-Report.pdf​​
5. Farrell PM, White TB, Ren CL, et al. Diagnosis of cystic fibrosis: consensus guidelines from the cystic fibrosis foundation. J Pediatr. 2017;181S:S4–S15.e1.
6. Konstan MW, Butler SM, Wohl ME, et al. Growth and nutritional indexes in early life predict pulmonary function in cystic fibrosis. J Pediatr. 2003 Jun;142(6):624–630.
7. Yen EH, Quinton H, Borowitz D. Better nutritional status in early childhood is associated with improved clinical outcomes and survival in patients with cystic fibrosis. J Pediatr. 2013;162:530–535 e531.
8. McColley SA, Schechter MS, Morgan WJ, et al. Risk factors for mortality before age 18 years in cystic fibrosis. Pediatr Pulmonol. 2017;52:909–915.
9. van Goor F, Hadida S, Grootenhuis PD, et al. Correction of the Phe-508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A. 2011;108:18843–18848.
10. Ren HY, Grove DE, de la Rosa O, et al. VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1. Mol Biol Cell. 2013;24:3016–3024.
11. Flume PA, Liou TG, Borowitz DS, et al. Ivacaftor in subjects with cystic fibrosis who are homozygous for the Phe-508del-CFTR mutation. Chest. 2012;142:718–724.
12. Clancy JP, Rowe SM, Accurso FJ, et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax. 2012;67:12–18.
13. Boyle MP, Bell SC, Konstan MW, et al. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014;2:527–538.
14. Vertex Drug Information. [cited 2017 Aug 6]. Available from: http://pi.vrtx.com/files/uspi_lumacaftor_ivacaftor.pdf​​
15. ClinicalTrials.gov. A service of the National ClinicalTrials.gov. A service of the National Institutes of Health. [cited 2017 May 24]. Available from: http://www.clinicaltrials.gov/ct2/results?term=CFTR&Search=Search. Institutes of Health. http://www.clinicaltrials.gov/ct2/results?term=CFTR&Search=Search [Accessed 6 August 2017]​​
16. Rowe SM, McColley SA, Rietschel E, et al. Lumacaftor/ivacaftor treatment of patients with cystic fibrosis heterozygous for Phe-508del-CFTR. Ann Am Thorac Soc. 2017;14:213–219.
17. Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor-ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med. 2015;373:220–231.
18. Konstan MW, McKone EF, Moss RB, et al. Assessment of safety and efficacy of long-term treatment with combination lumacaftor and ivacaftor therapy in patients with cystic fibrosis homozygous for the Phe-508del-CFTR mutation (PROGRESS): a phase 3, extension study. Lancet Respir Med. 2017;5:107–118.
19. Milla CE, Ratjen F, Marigowda G, et al. Lumacaftor/ivacaftor in patients aged 6–11 years with cystic fibrosis and homozygous for Phe-508del-CFTR. Ajrccm. 2017;195:912–920.
20. Ratjen F, Hug C, Marigowda G, et al. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2017;5:557–567.
21. Deeks ED. Lumacaftor/ivacaftor: a review in cystic fibrosis. Drugs. 2016;76:1191–1201.
22. McColley SA. Combination lumacaftor and ivacaftor therapy for cystic fibrosis. Expert Opin Orphan Drugs. 2016. DOI:10.1517/21678707.2016.1133282​​
23. Kuk K, Taylor-Cousar JL. Lumacaftor and ivacaftor in the management of patients with cystic fibrosis: current evidence and future prospects. Ther Adv Respir Dis. 2015;9:313–326.
24. McColley SA. A safety evaluation of ivacaftor for the treatment of cystic fibrosis. Expert Opin Drug Saf. 2016. DOI:10.1517/14740338.2016.116566
25. Heltshe SL, Mayer-Hamblett N. Rowe S. Pseudomonas aeruginosa in cystic fibrosis patients with G551D-CFTR treated with ivacaftor et al. Clin Infect Dis. 2015;60:703–712.
26. [cited 2017 Aug 5]. Available from: https://www.accessdata.fda.gov/scripts/cder/safetylabelingchanges/index.cfm?event=searchdetail.page&DrugNameID=234​​
27. Cholon DM, Quinney NL, Fulcher ML, et al. Potentitor ivacaftor abrogates pharmachological correction of ∆F508 CFTR in cystic fibrosis. Sci Transl Med. 2014;6:246ra96.
28. Veit G, Avramescu RG, Perdomo D, et al. Some gating potentiators, including VX-770, diminish ∆F508 CFTR functional expression. Sci Transl Med. 2014;6:246ra97.
29. Vertex press release. [cited 2017 Aug 7]. Available from: http://investors.vrtx.com/releasedetail.cfm?ReleaseID=1019156​​
30. Vertex press release. [cited 2017 Aug 7]. Availble from: http://investors.vrtx.com/releasedetail.cfm?ReleaseID=995364​​