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Indian Pediatr 2019;56: 1065-1066 |
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Treatment of Neonatal Seizures: Levetiracetam vs
Phenobarbitone
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BS Madarkar 1
and P Kaur2
1Department of Neonatology, Prashanthi
Hospital, Warangal, Telangana, and 2Department of Pediatrics,
Lady Hardinge Medical College, New Delhi; India.
Email:
[email protected]
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We read the recent study by Vykuntaraju, et al. [1] with great
interest. Phenobarbitone, the currently used first line antiepileptic
drug in neonatal seizures, has been associated with increased neuronal
apoptosis in animal models and cognitive impairment in humans. This well
conducted randomized controlled trial comparing levetiracetam to
pheonobarbitone addressed a relevant question. A few queries; however,
emerge:
1) Sample size was calculated considering the
proportion of outcomes in levetiracetam group to be 77% [2].
However, the reference study [2] had a higher
proportion of premature babies, and electrographic seizure
resolution was documented, which was not the case in present study
[1]. Hence, a larger sample size might have been required. Also,
same sample size cannot be used to calculate both safety as well as
efficacy, as has been done in this study.
2) Baseline characteristics in both groups
demonstrated hypoxic ischemic encephalopathy (HIE) as the
predominant etiology; HIE stages, however, have not been specified.
HIE stage 2 could show better response than stage 3.
Subclassification could have avoided any unintentional bias.
3) Levetiracetam has been approved for use in
children aged more than 4 and adults by the US Food and Drug
Administration as an adjuvant drug. Hence, neonatal use as an
off-label drug [3] may
pose an ethical dilemma.
4) Neonates have lower plasma clearance and
higher volume of distribution; hence, longer half-life of
levetiracetam as compared to adults [4]. Most studies in small
population groups, have been insufficient to understand the
pharmacokinetics and advocate routine use in neonates.This confusion
is amplified by various studies where doses as low as 10 mg/kg/day
and as high as 80 mg/kg/day have been used. Appropriate neonatal
dose needs to be established through phase II trials.
References
1. Gowda VK, Romana A, Shivanna NH, Benakappa N,
Benakappa A. Levetiracetam versus phenobarbitone in neonatal seizures –
A randomized controlled trial. Indian Pediatr. 2019;58:643-6.
2. Ramantani G, Ikonomidou C, Walter B.
Levetiracetam: Safety and efficacy in neonatal seizures. Eur J
Paediatr Neurol. 2011;15:1-7.
3. Silverstein FS, Ferriero DM. Off-label use of
antiepileptic drugs for the treatment of neonatal seizures. Pediatr
Neurol. 2008;39:77-9.
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