International Journal of Medical and Pharmaceutical Case Reports

Aims: This case report aims to describe the cardiac and metabolic complications arising from concurrent use of phenytoin and dual beta-blocker therapy in a patient with hypertension and a history of seizures, and to highlight the importance of medication reconciliation, electrolyte monitoring, and follow-up adherence in complex polypharmacy scenarios.

Presentation of Case: A 64-year-old man with hypertension and long-standing tremors developed ventricular premature complexes (VPCs) and severe hyponatraemia (serum sodium 103 mEq/L) while on phenytoin, levetiracetam, and dual beta-blockers (propranolol and metoprolol). He presented with first-degree atrioventricular (AV) block on ECG and required hospitalisation for hypertonic saline and tolvaptan therapy. Missed nephrology follow-up led to propranolol reinitiation, and first-degree AV block recurred during a subsequent admission for bilateral wrist arthritis, with a subtherapeutic serum phenytoin concentration (<3 µg/mL), suggesting free phenytoin toxicity from hypoalbuminaemia.

Discussion: Concurrent use of phenytoin and dual beta-blockers created a synergistic negative dromotropic environment. Phenytoin-associated SIADH likely mediated hyponatraemia, further destabilising cardiac depolarisation. Protein-binding displacement and CYP450 induction contributed to pharmacokinetic complexity despite apparently low total phenytoin levels. Missed follow-up perpetuated polypharmacy risk.

Conclusion: Concurrent phenytoin and dual beta-blocker therapy can precipitate AV block and hyponatraemia even at subtherapeutic serum levels. Strict medication reconciliation, regular ECG and electrolyte monitoring, and follow-up adherence are essential when managing patients on multiple agents with overlapping cardiac and metabolic effects.