Elsevier

Pediatric Neurology

Volume 39, Issue 2, August 2008, Pages 77-79
Pediatric Neurology

Original article
Off-Label Use of Antiepileptic Drugs for the Treatment of Neonatal Seizures

https://doi.org/10.1016/j.pediatrneurol.2008.04.008Get rights and content

Medically refractory neonatal seizures represent a major therapeutic challenge in neonatal intensive care units. Conventional antiepileptic drugs demonstrate limited efficacy. Previous studies documented a high frequency of off-label drug therapy in neonates. We sought to determine if pediatric neurologists are recommending treatment of neonatal seizures with newer agents, despite a lack of information about their safety or efficacy in this population. Surveys were distributed at the 2007 Annual Meeting of the Child Neurology Society. Responses from 55 pediatric neurologists were analyzed. Seventy-three percent (40/55) recommended treatment of neonatal seizures with one or both of levetiracetam and topiramate; 47% (26/55) recommended levetiracetam; and 55% (30/55) recommended topiramate. Despite an absence of data on neonatal pharmacokinetics of either drug, neurologists made different dosing recommendations for these two drugs (P = 0.003, chi-square test). Respondents considered both agents to be efficacious in the majority of cases; adverse effects were recognized more frequently with topiramate. These results highlight the urgent need for rigorous clinical trials to understand the risks and benefits of new drug therapies for neonatal seizures.

Introduction

The treatment of neonatal seizures is often unsatisfactory. Despite evidence from a rigorously conducted clinical trial that the administration of phenobarbital or phenytoin was effective in less than 50% of cases [1], almost a decade later, these drugs remain the most common treatment for neonatal seizures [2]. A recent survey of 5 American neonatal intensive care units showed that anticonvulsant therapy is initiated in over 94% of neonates with seizures, and that phenobarbital is the drug of first choice for 82% [3].

There is a paucity of data regarding the pharmacokinetics of many drugs and interactions among medications in neonates, and “off-label” drug use is very common in this age group [4], [5]. Although neonatologists frequently initiate treatment for neonatal seizures, they often consult pediatric neurologists if seizures recur after the administration of a loading dose of phenobarbital. Over the past decade, several newer antiepileptic drugs have gained wide acceptance in pediatric neurology practice. Anecdotal reports suggest that some of these antiepileptic drugs are being used to treat neonatal seizures. To gain an understanding of this rapidly evolving practice, we surveyed pediatric neurologists about their recommendations for the treatment of neonatal seizures with newer antiepileptic drugs. We hypothesized that 2 drugs, levetiracetam and topiramate, would be recommended more frequently than other newer antiepileptic drugs, and we focused on these agents.

Section snippets

Methods and Results

At the 2007 Annual Meeting of the Child Neurology Society, surveys were distributed at a poster presentation that discussed the treatment of neonatal seizures [6], and at a meeting of the Neonatal Neurology Interest Group. Fifty-five completed surveys were collected. All respondents were pediatric neurologists, and all but one indicated that they consulted in neonatal intensive care units. Forty respondents were in academic practice, 12 were in hospital-based or private practice, and 3 were in

Discussion

Published guidelines for levetiracetam and topiramate in one of the most commonly used pharmacy references, the Micromedex Healthcare Series-Drugdex, reveal that no information is available for levetiracetam regarding its use as an intravenous formulation for children less than 16 years old, and for the oral formulation, no information is available about safety or efficacy for children below age 4 years. For topiramate, the entry states, “Efficacy in seizures not established in children under 2

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