Cardiovascular adverse effects of phenytoin

J Neurol. 2016 May;263(5):861-870. doi: 10.1007/s00415-015-7967-1. Epub 2015 Dec 8.


Phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus. One of its main advantages over benzodiazepines is the less sedative effect. However, the possibility of cardiovascular adverse effects with the intravenous use of phenytoin cause a reluctance to its usage, and this has lead to a search for safer anticonvulsant drugs. In this study, we aimed to review the studies which evaluated the safety of phenytoin with respect to cardiovascular adverse effects. The original clinical trials and case reports listed in PUBMED in English language between the years of 1946-2014 were evaluated. As the key words, "phenytoin, diphenylhydantoin, epilepsy, seizure, cardiac toxicity, asystole, arrhythmia, respiratory arrest, hypotension, death" were used. Thirty-two clinical trials and ten case reports were identified. In the case reports, a rapid infusion rate (>50 mg/min) of phenytoin appeared as the major cause of increased mortality. In contrast, no serious cardiovascular adverse effects leading to death were met in the clinical trials which applied the recommended infusion rate and dosages. An infusion rate of 50 mg/min was reported to be safe for young patients. For old patients and patients with a cardiovascular co-morbidity, a slower infusion rate was recommended with a careful follow-up of heart rhythm and blood pressure. No cardiovascular adverse effect was reported in oral phenytoin overdoses except one case with a very high serum phenytoin level and hypoalbuminemia. Phenytoin is an effective and well tolerated drug in the treatment of epilepsy. Intravenous phenytoin is safe when given at recommended infusion rates and doses.

Keywords: Arrhythmia; Cardiovascular adverse effects; Death; Epilepsy; Phenytoin.

Publication types

  • Review

MeSH terms

  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects*
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular System / drug effects*
  • Humans
  • Phenytoin / administration & dosage
  • Phenytoin / adverse effects*


  • Anticonvulsants
  • Phenytoin