Introduction

Status epilepticus is a neurological emergency that required urgent assessment and treatment with pharmacologic agents
Lorazepam and diazepam are short-acting drugs that can produce immediate effects.
Treatment with another long-acting anticonvulsant drug is necessary to prevent recurrent convulsions.
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.
However, both PHT and FPHT can induce adverse reactions such as a reduction in blood pressure, arrhythmia, and allergic symptoms.

Pharmacology

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 Dizziness Irritability
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

References

Phenytoin. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved November 12, 2018, from http://www.micromedexsolutions.com/
Levetiracetam. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved November 12, 2018, from http://www.micromedexsolutions.com/
Alvarez V. Second-line status epilepticus treatment: comparison of phenytoin, valproate, and levetiracetam. Epilepsia. 2011 Jul;52(7):1292-6.
Chakravarthi S. Levetiracetam versus phenytoin in management of status epilepticus. J Clin Neurosci. 2015 Jun;22(6):959-63.
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.
Gujjar AR. Intravenous levetiracetam vs phenytoin for status epilepticus and cluster seizures: A prospective, randomized study. Seizure. 2017 Jul;49:8-12.
Nakamura K. Efficacy of levetiracetam versus fosphenytoin for the recurrence of seizures after status epilepticus. Medicine (Baltimore). 2017 Jun;96(25):e7206
Bleck T. The established status epilepticus trial 2013. Epilepsia. 2013 Sep;54 Suppl 6:89-92.