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EcLiPSE – Should Levetiracetam Replace Phenytoin for Pediatric Status Epilepticus?

July 5, 2019

Written by Clay Smith

Spoon Feed
There was no difference in levetiracetam vs phenytoin as second-line agents after benzodiazepines for pediatric status epilepticus (SE) in median time to seizure cessation. Levetiracetam may have other advantages, as it is able to be given over 5 minutes (vs 20 minutes for phenytoin) and may cause fewer adverse effects.

Why does this matter?
Benzodiazepines are first-line therapy for SE in children. We often add a longer acting anticonvulsant second-line. In the UK, phenytoin is recommended but may cause issues, such as hypotension or allergic reactions, plus it takes longer to infuse. Is levetiracetam a good second-line option?

What’s the status on this seizure drug?
This was an open-label multicenter RCT with 296 children 6 months to 18 years who had SE and had gotten first-line benzodiazepines and needed a second line anticonvulsant, either levetiracetam 40mg/kg over 5 minutes or phenytoin 20mg/kg over 20 minutes. The primary outcome was time to cessation of seizure. In the levetiracetam patients, cessation of seizure activity occurred at a median time of 35 minutes; in the phenytoin group, 45 minutes. This difference was not statistically significant. One patient in the phenytoin group had life-threatening hypotension related to the infusion. Given that the two drugs are at least equally efficacious and that levetiracetam may be given faster and perhaps with less risk of side effects, it may be the better option as a second line drug behind benzos.

Another Spoonful
Another RCT, ConSEPT, studying the same thing also came out in the Lancet. It found no difference in the two drugs for the primary outcome of seizure cessation at 5 minutes after drug infusion (though phenytoin takes 20 minutes and levetiracetam takes 5 minutes).

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019 May 25;393(10186):2125-2134. doi: 10.1016/S0140-6736(19)30724-X. Epub 2019 Apr 17.

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What are your thoughts?