{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T11:27:57Z","timestamp":1774351677621,"version":"3.50.1"},"reference-count":11,"publisher":"The Pediatric Pharmacy Association","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.5863\/1551-6776-25.1.4","type":"journal-article","created":{"date-parts":[[2019,12,30]],"date-time":"2019-12-30T20:44:18Z","timestamp":1577738658000},"page":"4-6","source":"Crossref","is-referenced-by-count":4,"title":["Status Epilepticus: The Slow and Agonizing Death of Phenytoin"],"prefix":"10.5863","volume":"25","author":[{"given":"Elizabeth A.","family":"Hall","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Wheless","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie J.","family":"Phelps","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3883","reference":[{"issue":"8","key":"i1551-6776-25-1-4-b1","series-title":"JAMA","first-page":"1062","article-title":"Landmark article Sept 17, 1938: Sodium diphenyl hydantoinate in the treatment of convulsive disorders. By H. Houston Merritt and Tracy J. Putnam","volume":"251","year":"1984","unstructured":"Merritt\n              HH\n            , PutnamTJ.\n          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\u20131067."},{"issue":"suppl 1","key":"i1551-6776-25-1-4-b2","series-title":"J Child Neurol","first-page":"S11","article-title":"Pediatric use of intravenous and intramuscular phenytoin: lessons learned","volume":"13","year":"1998","unstructured":"Wheless\n              JW.\n            \n          \n          Pediatric use of intravenous and intramuscular phenytoin: lessons learned. J Child Neurol. 1998;13(suppl 1):S11\u2013S14."},{"issue":"1","key":"i1551-6776-25-1-4-b3","series-title":"Epilepsy Curr","first-page":"48","article-title":"Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society","volume":"16","year":"2016","unstructured":"Glauser\n              T\n            , ShinnarS, GlossD, \n          et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48\u201361."},{"issue":"3","key":"i1551-6776-25-1-4-b4","series-title":"Seizure","first-page":"167","article-title":"The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published studies","volume":"23","year":"2014","unstructured":"Yasiry\n              Z\n            , ShorvonSD.\n          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\u2013174."},{"issue":"2","key":"i1551-6776-25-1-4-b5","series-title":"Neurology","first-page":"202","article-title":"Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin","volume":"38","year":"1988","unstructured":"Shaner\n              DM\n            , McCurdySA, HerringMO, \n          et al. Treatment of status epilepticus: a prospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Neurology. 1988;38(2):202\u2013207."},{"issue":"12","key":"i1551-6776-25-1-4-b6","series-title":"N Engl J Med","first-page":"792","article-title":"A comparison of four treatments for generalized convulsive status epilepticus Veterans Affairs Status Epilepticus Cooperative Study Group","volume":"339","year":"1998","unstructured":"Treiman\n              DM\n            , MeyersPD, WaltonNY, \n          et al. A comparison of four treatments for generalized convulsive status epilepticus Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998;339(12):792\u2013798."},{"issue":"6","key":"i1551-6776-25-1-4-b7","series-title":"J Clin Neurosci","first-page":"959","article-title":"Levetiracetam versus phenytoin in management of status epilepticus","volume":"22","year":"2015","unstructured":"Chakravarthi\n              S\n            , GoyalMK, ModiM, \n          et al. Levetiracetam versus phenytoin in management of status epilepticus. J Clin Neurosci. 2015;22(6):959\u2013963."},{"issue":"6","key":"i1551-6776-25-1-4-b8","series-title":"Seizure","first-page":"527","article-title":"Randomized study of intravenous valproate and phenytoin in status epilepticus","volume":"16","year":"2007","unstructured":"Agarwal\n              P\n            , KumarN, ChandraR, \n          et al. Randomized study of intravenous valproate and phenytoin in status epilepticus. Seizure. 2007;16(6):527\u2013532."},{"issue":"10186","key":"i1551-6776-25-1-4-b9","series-title":"Lancet","first-page":"2135","article-title":"Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial","volume":"393","year":"2019","unstructured":"Dalziel\n              SR\n            , BorlandML, FurykJ, \n          et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019;393(10186):2135\u20132145."},{"issue":"10186","key":"i1551-6776-25-1-4-b10","series-title":"Lancet","first-page":"2125","article-title":"Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial","volume":"393","year":"2019","unstructured":"Lyttle\n              MD\n            , RainfordNEA, GambleC, \n          et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019;393(10186):2125\u20132134."},{"issue":"20","key":"i1551-6776-25-1-4-b11","series-title":"Neurology","first-page":"e2339","article-title":"Meta-analysis and cost-effectiveness of second-line antiepileptic drugs for status epilepticus","volume":"92","year":"2019","unstructured":"Sanchez Fernandez\n              I\n            , Gainza-LeinM, LambN, \n          et al. Meta-analysis and cost-effectiveness of second-line antiepileptic drugs for status epilepticus. Neurology. 2019;92(20):e2339\u2013e2348."}],"container-title":["The Journal of Pediatric Pharmacology and Therapeutics"],"original-title":[],"link":[{"URL":"https:\/\/jppt.kglmeridian.com\/view\/journals\/jppt\/25\/1\/article-p4.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/meridian.allenpress.com\/jppt\/article-pdf\/25\/1\/4\/2466823\/1551-6776-25_1_4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jppt.kglmeridian.com\/downloadpdf\/journals\/jppt\/25\/1\/article-p4.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jppt.kglmeridian.com\/downloadpdf\/journals\/jppt\/25\/1\/article-p4.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:38:07Z","timestamp":1747355887000},"score":1,"resource":{"primary":{"URL":"https:\/\/jppt.kglmeridian.com\/view\/journals\/jppt\/25\/1\/article-p4.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":11,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.5863\/1551-6776-25.1.4","relation":{},"ISSN":["1551-6776"],"issn-type":[{"value":"1551-6776","type":"print"}],"subject":[],"published":{"date-parts":[[2020]]}}}