Status Epilepticus: The Slow and Agonizing Death of Phenytoin
- PMID: 31897070
- PMCID: PMC6938285
- DOI: 10.5863/1551-6776-25.1.4
Status Epilepticus: The Slow and Agonizing Death of Phenytoin
Abstract
Since its introduction in 1950, phenytoin (PHT) has been the premier parenteral anticonvulsant used in the management of generalized convulsive status epileptics (GCSE) that is refractory to benzodiazepines. Without question, its arrival was vital to the care of patients with acute seizures and was a welcomed alternative to paraldehyde and phenobarbital. However, after more than half a century of use, there continues to be insufficient evidence-based data to support its efficacy over other anticonvulsants as a first-line agent in pediatric or adult patients with GCSE. This coupled with its narrow mechanism of action, complex pharmacokinetics and pharmacogenomics, drug-drug interactions, unique adverse effects, and formulation issues that make administration difficult mandates that PHT be replaced by safer and superiorly effective anticonvulsants for the treatment of GCSE when benzodiazepines are ineffective. We believe that levetiracetam should become the preferred agent for seizures unresponsive to or recurring after treatment with a benzodiazepine as it is at least equally effective to PHT and has several important advantages. PHT has overstayed its welcome and it is simply time for it to exit the realm of acute seizure management as a first-line agent for benzodiazepine-refractory GCSE.
Keywords: epilepsy; fosphenytoin; guidelines; levetiracetam; phenytoin; status epilepticus.
Copyright Published by the Pediatric Pharmacy Association. All rights reserved. For permissions, mhelms@pediatricpharmacy.org 2020.
Conflict of interest statement
Disclosure Drs Hall and Phelps declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. Dr Wheless has been a consultant to and received research funding from UCB, Inc.
Similar articles
-
Refractory generalised convulsive status epilepticus : a guide to treatment.CNS Drugs. 2005;19(9):759-68. doi: 10.2165/00023210-200519090-00003. CNS Drugs. 2005. PMID: 16142991 Review.
-
Generalized convulsive status epilepticus.Mayo Clin Proc. 1996 Aug;71(8):787-92. doi: 10.1016/S0025-6196(11)64844-1. Mayo Clin Proc. 1996. PMID: 8691900
-
Management approaches to prolonged seizures and status epilepticus.Epilepsia. 1999;40 Suppl 1:S59-63; discussion S64-6. doi: 10.1111/j.1528-1157.1999.tb00880.x. Epilepsia. 1999. PMID: 10421562 Review.
-
Clinical Effectiveness of Levetiracetam Compared to Fosphenytoin in the Treatment of Benzodiazepine Refractory Convulsive Status Epilepticus.Indian J Pediatr. 2020 Jul;87(7):512-519. doi: 10.1007/s12098-020-03221-2. Epub 2020 Feb 22. Indian J Pediatr. 2020. PMID: 32088913 Clinical Trial.
-
Levetiracetam versus phenytoin in management of status epilepticus.J Clin Neurosci. 2015 Jun;22(6):959-63. doi: 10.1016/j.jocn.2014.12.013. Epub 2015 Apr 18. J Clin Neurosci. 2015. PMID: 25899652 Clinical Trial.
Cited by
-
Treatments for Convulsive and Nonconvulsive Status Epilepticus in Adults: An Expert Opinion Survey in South Korea.J Clin Neurol. 2021 Jan;17(1):20-25. doi: 10.3988/jcn.2021.17.1.20. J Clin Neurol. 2021. PMID: 33480194 Free PMC article.
-
Pre-hospital and emergency department treatment of convulsive status epilepticus in adults: an evidence synthesis.Health Technol Assess. 2022 Mar;26(20):1-76. doi: 10.3310/RSVK2062. Health Technol Assess. 2022. PMID: 35333156 Free PMC article.
-
Oral Use of Phenytoin to Reduce Calcification in Bovine Pericardium and Porcine Aortic Leaflets Implants in Rats.Braz J Cardiovasc Surg. 2021 Jun 1;36(3):295-300. doi: 10.21470/1678-9741-2020-0252. Braz J Cardiovasc Surg. 2021. PMID: 34387971 Free PMC article.
References
-
- Merritt HH, Putnam TJ. Landmark article Sept 17, 1938: Sodium diphenyl hydantoinate in the treatment of convulsive disorders. By H. Houston Merritt and Tracy J. Putnam. JAMA. 1984;251(8):1062–1067. - PubMed
-
- Wheless JW. Pediatric use of intravenous and intramuscular phenytoin: lessons learned. J Child Neurol. 1998;13(suppl 1):S11–S14. - PubMed
-
- Yasiry Z, Shorvon SD. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published studies. Seizure. 2014;23(3):167–174. - PubMed
-
- Shaner DM, McCurdy SA, Herring MO et al. Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Neurology. 1988;38(2):202–207. - PubMed
Publication types
LinkOut - more resources
Full Text Sources