Serum levels of Elexacaftor/Tezacaftor/Ivacaftor in children and adolescents with cystic fibrosis

Background: CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor (ETI) is a cornerstone of cystic fibrosis (CF) treatment. Whether the manufacturer’s three fixed dosage levels adequately account for changes in body weight and composition in growing children remains unclear. In addition, drug–drug interactions and dose reductions due to adverse effects highlight the need for therapeutic drug monitoring (TDM). Methods: Routinely collected blood samples from paediatric people with CF (pwCF) treated at the Children’s Hospital Heidelberg between November 2023 and March 2025 were analysed using isotope dilution liquid chromatography–tandem mass spectrometry (ID-LC-MS/MS) at LMU University Hospital Munich (Habler et al., 2021, DOI: 10.1515/cclm-2021-0724). Serum concentrations were compared with maximum drug concentrations (C_max) reported in the manufacturer’s summary of product characteristics, stratified by whether the full recommended dose was administered and whether sampling occurred within the median time to reach C_max (t_max). Results: In total, 63 samples from 46 pwCF (43.5% female) were analysed. Among pwCF that received the full dose, in samples obtained within t_max, serum concentrations exceeding C_max± standard deviation (SD) were observed in 30%, 20%, and 11.8% of cases for elexacaftor, tezacaftor, and ivacaftor, respectively. Concurrently, 50%, 53.3%, and 58.8% of samples fell within the C_max± SD range. Conclusions: Serum concentrations above the recommended target ranges are also observed in paediatric patients, although less frequently than reported in adults (Naehrig et al., 2024, DOI: 10.3390/jpm14101065). These findings support the feasibility of low-threshold dose reductions in the presence of drug interactions or adverse effects, preferably guided by therapeutic drug monitoring. Publication History Article published online: 26 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany