Safety and Effectiveness of Levetiracetam and Phenytoin as Second-line Drugs in Neonatal Seizures

Introduction Neonatal seizures are often refractory to first-line treatment, such as phenobarbital. Levetiracetam and phenytoin are commonly used second-line drugs to treat neonatal seizures, but they have not been directly compared. The objective of this study was to compare the safety and effectiveness of levetiracetam and phenytoin as second-line drugs for neonatal seizures. Methods A retrospective cohort study was conducted of neonates given levetiracetam or phenytoin following phenobarbital for neonatal seizures. The association with levetiracetam or phenytoin and adverse drug events (ADEs) was assessed using the Naranjo scale. Effectiveness was defined as the need for a third-line antiepileptic drug. Results One hundred and fifty-two patients were included in this study: 75 patients in the levetiracetam group and 77 patients in the phenytoin group. A higher proportion of patients in the phenytoin group (21%) experienced one or more ADEs compared to the levetiracetam group (8%) ( P = .025). The most common ADE in the phenytoin group was hypotension (13%), and it was more frequent compared to levetiracetam (1.3%) ( P = .006). The most common ADE in the levetiracetam group was irritability (4%). The use of a third-line antiepileptic drug was similar between levetiracetam (60%) and phenytoin (62%) ( P = .78). Conclusion ADEs were more frequent in the phenytoin group compared to the levetiracetam group. Levetiracetam and phenytoin were similarly effective in treating neonatal seizures. However, both second-line drugs still have less than optimal effectiveness. Randomized controlled trials are needed to confirm these results.