Recurrent fexuprazan-induced liver injury following unintentional re-exposure

Fexuprazan, a potassium-competitive acid blocker, is increasingly used for the treatment of gastroesophageal reflux disease in South Korea. While generally well tolerated, data regarding its hepatotoxic potential are scarce. We report a case of idiosyncratic drug-induced liver injury in a 61-year-old woman following 2 months of fexuprazan therapy. She presented with fatigue and elevated liver enzymes, and liver biopsy demonstrated single-cell necrosis, interface hepatitis and eosinophilic infiltration-features consistent with drug-induced liver injury. Her liver function normalized after drug discontinuation. However, approximately 20 months later, the patient experienced a recurrence of liver injury after unintentionally being prescribed fexuprazan again. The second episode showed similar biochemical and histological features, fulfilling Hy's law criteria and increasing the RUCAM score from probable to highly probable. Pharmacokinetic analysis during the first episode revealed a prolonged elimination half-life, suggestive of impaired metabolism during active hepatic injury. Pharmacogenetic testing revealed a cytochrome P450 enzyme 2C19 poor metabolizer genotype, although its clinical relevance was limited in this case. This report highlights a rare but reproducible adverse drug reaction to fexuprazan and emphasizes the importance of thorough drug history and postmarketing surveillance. To our knowledge, this is the first report of recurrent fexuprazan-induced liver injury confirmed by unintentional re-exposure.