Intravenous brivaracetam in status epilepticus: A retrospective single‐center study

Abstract

Brivaracetam (BRV) is a high-affinity synaptic vesicle glycoprotein 2A ligand that is structurally related to levetiracetam (LEV). Compared to LEV, its affinity to the ligand is >10%-30% higher. Due to its more lipophilic characteristics, it might have a quicker penetration across the blood-brain barrier and potentially also a stronger anticonvulsant effect. Thus, we aimed to explore its usefulness in the treatment of status epilepticus (SE). We retrospectively assessed treatment response and adverse events in adjunctive treatment with intravenous BRV in patients with SE from January 2016 to July 2017 at our institution. Seven patients aged median 68 years (range = 29-79) were treated with intravenous BRV. Three patients had SE with coma and four without. SE arose de novo in two patients; etiology was remote symptomatic in four patients and progressive symptomatic in one patient. The most frequent etiology was remote vascular in two patients. BRV was administered after median four antiepileptic drugs (range = 2-11). Time of treatment initiation ranged from 0.5 hours to 105 days (median = 10.5 hours). Immediate clinical and electrophysiological improvement was observed in two patients (29%). Median loading dose was 100 mg intravenously over 15 minutes (range = 50-200 mg), titrated up to a median dose of 100 mg/d (range = 100-300). Median Glasgow Outcome Scale score was 3 (range = 3-5), with an improvement in 86% of patients compared to admission. We observed no adverse events regarding cardiorespiratory function. BRV might have potential as a novel antiepileptic drug in early stages of SE. Its potential may lie its ability to cross the blood-brain barrier more quickly than LEV and its favorable safety profile. Prospective studies for the use of BRV in SE are required.

A single‐center, open‐label positron emission tomography study to evaluate brivaracetam and levetiracetam synaptic vesicle glycoprotein 2A binding in healthy volunteers

“…The corrected half‐times for 100 mg BRV and 1500 mg LEV in this clinical study are similar to the 3‐minute and 23‐ minute half‐times observed in the nonhuman primate study at doses intended to result in equivalent plasma levels in humans. Despite neither BRV nor LEV being indicated for SE, recent studies have suggested that SE patients can be treated with BRV, with loading doses similar to those in this study . A further recent study has reported that a human dose of at least 2 mg/kg and up to 5 mg/kg is necessary for efficacy in SE, suggesting that doses slightly above 100 mg BRV intravenously could be in the efficacious range .…”

Treatment of refractory and superrefractory status epilepticus with topiramate: A cohort study of 106 patients and a review of the literature

“…(mRS) scores at admission and discharge, and in responders and nonresponders to topiramate (TPM) [41][42][43] Two recent case series reported on the use of oral perampanel in patients with various stages of SE, reporting response rates between 17% 44 and 37%. 45 Use of oral oxcarbazepine in SE was reported in 13 patients with a median treatment latency of 81 hours.…”

Use of Newer Anticonvulsants for the Treatment of Status Epilepticus

“…Despite availability of animal studies showing potential benefits of BRV in treatment of SE, clinical evidence in SE is limited . Two clinical studies were identified (Table ) . A retrospective chart review was conducted of patients who had received BRV for SE.…”

“…No serious adverse effects were reported. Authors noted that BRV responders were treated earlier in the course of their SE compared with BRV nonresponders …”