Tolerability, safety, and side effects of levetiracetam versus phenytoin in intravenous and total prophylactic regimen among craniotomy patients: a prospective randomized study.

PURPOSE: Practical choice in parenteral antiepileptic drugs (AEDs) remains limited despite formulation of newer intravenous agents and requirements of special patient groups. This study aims to compare the tolerability, safety, and side effect profiles of levetiracetam (LEV) against the standard agent phenytoin (PHT) when given intravenously and in total regimen for seizure prophylaxis in a neurosurgical setting.

METHODS: This prospective, randomized, single-center study with appropriate blinding comprised evaluation pertaining to intravenous use 3 days following craniotomy and at discharge, and to total intravenous-plus-oral AED regimen at 90 days. Primary tolerability end points were discontinuation because of side effect and first side effect. Safety combined end point was major side effect or seizure. Seizure occurrence and side effect profiles were compared as secondary outcomes.

KEY FINDINGS: Of 81 patients randomized, 74 (36 LEV, 38 PHT) received parenteral AEDs. No significant difference attributable to intravenous use was found between LEV and PHT in discontinuation because of side effect (LEV 1/36, PHT 2/38, p = 1.00) or number of patients with side effect (LEV 1/36, PHT 4/38, p = 0.36). No significant difference was found between LEV and PHT total intravenous-plus-oral regimen in discontinuation because of side effect (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.21-2.92, p = 0.72) or number of patients with side effect (HR 1.51, 95% CI 0.77-2.98, p = 0.22). More patients assigned PHT reached the undesirable clinical end point for safety of major side effect or seizure (HR 0.09, 95% CI 0.01-0.70, p = 0.002). Seizures occurred only in patients assigned PHT (n = 6, p = 0.01). Although not significant, trends were observed for major side effect in more patients assigned PHT (p = 0.08) and mild side effect in more assigned LEV (p = 0.09).

SIGNIFICANCE: Both LEV and PHT are well-tolerated perioperatively in parenteral preparation, and in total intravenous-plus-oral prophylactic regimen. Comparative safety and differing side effect profile of intravenous LEV supports use as an alternative to intravenous PHT.