Efficacy and Safety of Fosphenytoin versus Phenobarbital for Convulsive Status Epilepticus and Cluster Seizures in Childhood: A Retrospective Single-Center Study

Abstract

Fosphenytoin (FOS) is a phosphate ester prodrug developed as an alternative to intravenous phenytoin for acute treatment of seizures. Although both FOS and phenobarbital (PB) are used for status epilepticus as second-line drugs, there is no data on their comparative efficacy and safety. We retrospectively analyzed data from children treated with FOS or PB for convulsive status epilepticus and acute exacerbation of seizures. Our aim was to compare the efficacy and safety of intravenous FOS with those of intravenous PB for convulsive status epilepticus and acute exacerbation of seizures. Seventy-seven children were included in the study: 54 received FOS, and 23 received PB. The primary end point was recurrence of seizures and drug-related adverse events. The response rate, defined as no recurrence of seizures within 24 hours after termination of seizure, was 92％ (50/54) and 95％ (22/23) in FOS group and in PB group, respectively. Adverse events occurred in 27％ (15/54) of patients in FOS group and in 95％ (22/23) of patients in PB group (P < 0.01). Although no serious adverse events occurred in patients in both FOS group and PB group, the incidence of both sedation and disturbance of consciousness were significantly higher in PB group than FOS group. From these results, FOS is recommended as second-line drugs for status epilepticus and acute exacerbation of seizures. However, the optimal serum concentration achievement rate was significantly lower in FOS group than PB group. To maintain optimal serum phenytoin levels (10 -20 µg/mL), higher doses of FOS might be required.