For patients unable to receive oral brivaracetam (BRV), an intravenous formulation administered as a bolus or infusion appears to be well tolerated, results of a phase 3 study indicate.
The findings of the multicenter, randomized, 4-arm, parallel-group study were published in Epilepsia.
Oral BRV has previously been proven effective as an adjunctive treatment for partial-onset seizures in adults with epilepsy. While antiepileptic drugs (AEDs) are typically administered orally, this may pose a problem in patients who are postoperative, in a coma, or for those who may have trouble swallowing. This study assessed the safety, tolerability, and pharmacokinetics of adjunctive intravenous BRV as either a 2-minute bolus or 15-minute infusion.
The study included 105 patients aged 16 to 70 years (mean age= 41.6 years; 53.3% women) of which 103 completed the study. Patients had focal or generalized epilepsy that was uncontrolled by 1 to 2 AEDs. Patients were randomized into 4 treatment arms: placebo/BRV bolus; placebo/BRV infusion; BRV tablets/BRV bolus; BRV tablets/BRV infusion. The primary outcome was the number of patients with at least one treatment-emergent adverse event. BRV plasma concentrations were measured both before and after last IV doses.
The incidence of treatment-emergent adverse events were similar whether IV BRV was initiated first (70.6%) or following oral BRV (66%), and whether it was administered as a bolus (71.2%) or infusion (65.4%). Overall, injection-related treatment-emergent adverse events were reported by 9.6% and 11.5% of patients following bolus or infusion, respectively. Notably, BRV plasma concentrations were higher after the first dose in the conversion groups vs the initiation groups, and marginally higher in the bolus vs infusion arms. Following the last dose, similar BRV concentrations were observed in all patients.
The most common treatment-emergent adverse events were somnolence (29.5%) and dizziness (14.3%) and were mild to moderate in intensity. One patient experienced severe vertigo and nausea, however no other severe adverse effects were reported.
“The similarity in treatment-emergent adverse events (TEAE) incidence between the initiation and conversion groups could indicate that IV administration of BRV in BRV-naive patients may be generally well tolerated with no requirement for uptitration,” the authors noted. “This is the case for oral BRV, which was administered with no uptitration in several previous studies.”
Overall, results indicate that IV BRV may be a safe, effective treatment option for patients unable to receive oral BRV.
Klein P, Biton V, Dilley D, Barnes M, Schiemann J, Lu S. Safety and tolerability of adjunctive brivaracetam as intravenous infusion or bolus in patients with epilepsy. Epilepsia. 2016; doi:10.1111/epi.13409.