Fosphenytoin vs Keppra for Status Epilepticus

All Pharmacy Pearls

Introduction

Status epilepticus is a neurological emeregnecy

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.

Clinical Detail

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.

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

IV Push ~3-15 min

5-2g IV over 7 min**

(2-5 mg/kg/min)

Formulation

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,

Evidence

Evidence details are preserved from the source document in the clinical sections and references.

Conclusions

Jun;96(25):e7206

Bleck T. The established status epilepticus trial 2013. Epilepsia. 2013 Sep;54 Suppl 6:89-92.

Kapur J, et al. “Randomized trial of three anticonvulsant medications for status epilepticus”. The New England Journal of Medicine. 2019.

381(22):2103-2113.

Dalziel SR, Borland ML, Furyk J, et al. (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019 May

25;393(10186):2135-2145.

Appleton RE, Rainford NE, Gamble Cet al. Levetiracetam as an alternative to phenytoin for second-line emergency treatment of children

with convulsive status epilepticus: the EcLiPSE RCT. Health Technol Assess. 2020 Nov;24(58):1-96.

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-

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-

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