Ivacaftor (Efficacy)
The FDA (U.S. Food and Drug Administration) approved drug ivacaftor is used in the treatment of cystic fibrosis in patients 1 month of age and older who have at least one mutation in the CFTR gene that responds to ivacaftor potentiation based on clinical and/or in vitro assay data.
MECHANISM OF ACTION
Ivacaftor is an enhancer of the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) protein. The drug increases the opening of the CFTR channel by promoting chloride transport in the CFTR protein. Thus, the reduction in CFTR channel opening produced by the above-mentioned mutations is compensated by the increase in channel opening generated by ivacaftor.
PRECAUTIONS
Precautions should be taken in patients with severe renal impairment or end-stage renal disease. Evaluate risk/benefit in severe hepatic insufficiency.
Precautions in concomitant use with moderate and potent CYP3A inhibitors or inducers.
For patients with increased aminotransferases (perform liver function tests before starting treatment, every 3 months for the first year and then annually), discontinue treatment.
In addition, use caution in prescribing in patients with ALAT or ASAT greater than 5 times the upper limit of normal.
Ivacaftor treatment is not recommended in transplant patients.
The safety and efficacy of ivacaftor in pediatric CF patients less than 1 month of age have not been established.
BRAND NAME
- Kalydeco®
Genes analyzed
Bibliography
Guerra L, D'Oria S, Favia M, et al.CFTR-dependent chloride efflux in cystic fibrosis mononuclear cells is increased by ivacaftor therapy. Pediatr Pulmonol. 2017 Jul;52(7):900-908.
Graeber SY, Vitzthum C, Pallenberg ST, et al. Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on CFTR Function in Patients with Cystic Fibrosis and One or Two F508del Alleles. Am J Respir Crit Care Med. 2022 Mar 1;205(5):540-549.
Ivacaftor (Kalydeco) 150 mg Tablet: For Treatment of Cystic Fibrosis with G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or G970R Mutation [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2015 Jul.
Regard L, Martin C, Da Silva J, Burgel PR. CFTR Modulators: Current Status and Evolving Knowledge. Semin Respir Crit Care Med. 2023 Apr;44(2):186-195.
Sawicki GS, Dasenbrook E, Fink AK, Schechter MS.Rate of Uptake of Ivacaftor Use after U.S. Food and Drug Administration Approval among Patients Enrolled in the U.S. Cystic Fibrosis Foundation Patient Registry. Ann Am Thorac Soc. 2015 Aug;12(8):1146-52.
Van Goor F, Yu H, Burton B, Hoffman BJ.Effect of ivacaftor on CFTR forms with missense mutations associated with defects in protein processing or function. J Cyst Fibros. 2014 Jan;13(1):29-36.
