Fosphenytoin vs Keppra for Status Epilepticus


  1. Status epilepticus is a neurological emergency that required urgent assessment and treatment with pharmacologic agents
  2. Lorazepam and diazepam are short-acting drugs that can produce immediate effects.
  3. Treatment with another long-acting anticonvulsant drug is necessary to prevent recurrent convulsions.
  4. Use of IV phenytoin (PHT) in the treatment of status epilepticus dates back to the 50s with fosphenytoin (FPHT) being the primary agent in some institutions.
  5. However, both PHT and FPHT can induce adverse reactions such as a reduction in blood pressure, arrhythmia, and allergic symptoms.


Properties  Phenytoin/ Fosphenytoin  Levetiracetam  (Keppra)  
Dose   20 mg/kg/PE   (max 1500 mg)  1-4.5 g IV   (40-60 mg/kg)*  
Administration  Max IV fusion   
PHT 50 mg/min   
FPHT 150 mg/min  
1g IV Push ~2 min**  
1.5-2g IV over 7 min**  
(2-5 mg/kg/min)  
Formulation  IV/PO  IV/PO  
PK/PD  Onset: ~30 min***  
Half Life: 12-28 hr
Excreted:  >90%   in urine  
Onset: 30-45 min  
Half-life: 6-8 hr  
Excreted: 66% renal  
Adverse Effect  Phlebitis, hypotension, bradycardia & dysrhythmias  Abnormal behavior   
Drug   Interactions and warnings  Major CYP3A4 Inducer (↓ drug levels)  —–  
Compatibility  PHT – only D5W  
FPHT- D5W or NS  
D5W or NS  
*GHS has utilized this administration based on clinical experience 
**PE= Phenytoin equivalents  
** Fosphenytoin takes 15 mins to be metabolized to active metabolite in addition to the infusion time

Overview of Evidence

   Author,  Year  Design/ sample   size  Dosing regimen   Outcome  
ESETT  RCT   N= >  VPA 30 mg/kg (max 3000 mg)          vs   LEV 60 mg/kg (max 4500mg)         vs   PHT 20 mg/kg (max 1500 mg)  Result expected 2020  
Nakamura, 2017  *Respective analysis/ n=63  LEV 1000 mg            vs   FPHT 22.5 mg/kg   No difference in control of seizure(81 vs 85.1%, p=0.69), adverse effects, or transition to PO antiepileptic drug   
Gujjar et al, 2017  *Prospective,   open-label   trial/   n=52  LEV 30 mg/kg            vs   PHT 20 mg/kg  LEV displayed no statistically significant difference than PHT in SE       Sequential use of these 92–97% of case controlled without anesthetic agents.  
Chakravarthi, 2017  *RCT n=44  LEV 20 mg/kg               vs   PHT 20 mg/kg  Both LEV and PHT were equally effective at termination of seizure activity within 30min and recurrence of seizures within 24 hours  
Mundlamuri,  2015  RCT/ n=150  VPA  30 mg/kg            vs   LEV 25 mg/kg           vs   PHT 20 mg/kg  No statistically significant difference in control of SE between VPA (68%), PHT (68 %,) and LEV (78%).   
Alvarez et al, 2011  Retrospective  analysis/ n=466  VPA  20 mg/kg   LEV 20 mg/kg   PHT 20 mg/kg  VPA controlled SE in 74.6%, PHT in 58.6% and LEV in 51.7% of episodes       LEV failed more often than VPA [odds ratio (OR) 2.69  
* Did not reach power according to sample size analysis or did not mention in methods


  1. Phenytoin. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved November 12, 2018, from http://www.micromedexsolutions.com/  
  2. Levetiracetam. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved November 12, 2018, from http://www.micromedexsolutions.com/  
  3. Alvarez V. Second-line status epilepticus treatment: comparison of phenytoin, valproate, and levetiracetam. Epilepsia. 2011 Jul;52(7):1292-6.
  4. Chakravarthi S. Levetiracetam versus phenytoin in management of status epilepticus. J Clin Neurosci. 2015 Jun;22(6):959-63.  
  5. Mundlamuri RC. Management of generalised convulsive status epilepticus (SE): A prospective randomised controlled study of combined treatment with intravenous lorazepam with either phenytoin, sodium valproate or levetiracetam–Pilot study. Epilepsy Res. 2015 Aug;114:52-8.  
  6. Gujjar AR. Intravenous levetiracetam vs phenytoin for status epilepticus and cluster seizures: A prospective, randomized study. Seizure. 2017 Jul;49:8-12.  
  7. Nakamura K. Efficacy of levetiracetam versus fosphenytoin for the recurrence of seizures after status epilepticus. Medicine (Baltimore). 2017 Jun;96(25):e7206  
  8. Bleck T. The established status epilepticus trial 2013. Epilepsia. 2013 Sep;54 Suppl 6:89-92.  

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