Pharmacokinetics and Pharmacodynamics of Levetiracetam in Neonatal Seizures: What We Still Need to Know.

Abstract

Neonatal seizures affect 1 to 4 neonates per 1000 live births and are associated with increased mortality and neurological impairment. Currently, phenobarbital is recommended as the first-line treatment; however, its limited efficacy and serious safety concerns are significant drawbacks. Levetiracetam, a newer generation anti-seizure medication with minimal reported adverse effects, is commonly used off label for the treatment of neonatal seizures. Earlier studies showed limited efficacy of levetiracetam in neonatal seizures; however, these studies were limited by the lack of pharmacokinetic-pharmacodynamic data for larger doses (>60 mg/kg). The pharmacokinetics of levetiracetam differ in neonates compared to children and adults. In neonates, the volume of distribution of levetiracetam can exceed that in children and adults. By 7 days of postnatal age, the clearance approaches that of children, which also exceeds the clearance reported in adults. There are limited pharmacodynamic studies of levetiracetam in neonatal seizures. Because the pathophysiology of seizures and the treatment goals in neonates differ from those in children and adults, critical information on the pharmacodynamics of levetiracetam at larger doses is still needed to confirm its efficacy or lack thereof.