Refractory hypokalemia associated with levetiracetam: a case report

Levetiracetam (LEV) is frequently prioritized in epilepsy management due to its minimal drug-drug interactions and perceived metabolic neutrality. However, its potential involvement in severe electrolyte disturbances remains scarcely documented. We describe a 36-year-old male admitted for status epilepticus and initiated on a dose-escalated LEV regimen (2000 mg/day). The clinical course was complicated by the development of severe, recalcitrant hypokalemia (nadir 2.8 mmol/L). This electrolyte depletion proved remarkably refractory to intensive parenteral and enteral potassium chloride supplementation. A systematic diagnostic workup successfully excluded extrarenal losses, primary hyperaldosteronism, and renal tubular acidosis. Given the specific temporal alignment with drug intensification, LEV was substituted with phenobarbital. This intervention led to a rapid and sustained restoration of potassium homeostasis within seven days post-withdrawal. Causality was evaluated as highly probable (I5; C2S3). This case, corroborated by recent large-scale epidemiological findings, highlights LEV as a potential trigger for refractory potassium depletion in the adult population. Unlike other antiepileptics, LEV lacks carbonic anhydrase inhibition, suggesting alternative mechanisms such as iatrogenic transcellular shifts or interference with renal ion conductance. We emphasize the necessity of rigorous metabolic monitoring during LEV dose escalation and advocate for an update to official safety labeling to include this metabolic risk, ensuring earlier clinical detection and improved patient safety.