Lumacaftor–Ivacaftor in Pediatric Patients With Cystic Fibrosis and Advanced Liver Disease: A Pilot Study

Abstract

Purpose: Lumacaftor–ivacaftor (LI) is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator for patients with cystic fibrosis homozygous for the F508del-CFTR variant. All CFTR modulators, including LI, are metabolized in the liver, and their use in advanced cystic fibrosis–related liver disease (ACFRLD) is not recommended due to concerns of worsening liver impairment, despite potential benefits for nutrition and lung function. Methods: A pilot study was conducted at the Queensland Children's Hospital, Australia, to describe the pharmacokinetics of LI and its metabolites (ivacaftor-M1 and ivacaftor-M6) in pediatric patients with ACFRLD. Three patients aged 4, 10, and 18 years..