The development of toxic drug-induced hepatitis in a slow metabolizer with cystic fibrosis

The increased risk of adverse drug reactions in patients with genetically determined features of drug metabolism is actively studied. The aim was to demonstrate the importance of taking into account pharmacogenetic features and drug interactions for the treatment of cystic fibrosis. Results. The article describes a case of toxic hepatitis in an 11-year-old child with cystic fibrosis (genotype F508del/F508del in the CFTR gene) and Gilbert’s syndrome (genotype 7TA/7TA in the UGT1A1 gene), who received targeted therapy with the drug elexacaftor/tezacaftor/ivacaftor + ivacaftor. The adverse reaction was provoked by interactions with other drugs, moderate CYP3A inhibitors (fluconazole and pyrantel) that were self-prescribed without consulting the doctor. Conclusion. When prescribing other drugs against the CFTR modulator treatment, it is necessary to take into account the interactions between the drugs according to the drug labels and it is advisable to determine the presence of Gilbert’s syndrome because of the lifelong use of targeted therapy.