Treatment of refractory and super-refractory status epilepticus with brivaracetam: A cohort study from two German university hospitals

Strzelczyk, Adam; Steinig, Isabel; Willems, Laurent M.; Reif, Philipp S.; Senft, Christian; Voss, Martin; Gaida, Bernadette; Podewils, Felix von; Rosenow, Felix

doi:10.1016/j.yebeh.2017.03.028

Cited by 72 publications

(74 citation statements)

References 20 publications

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“…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 .…”

Section: Discussionsupporting

confidence: 56%

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

et al. 2019

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Summary Objective Brivaracetam (BRV) and levetiracetam (LEV) are antiepileptic drugs that bind synaptic vesicle glycoprotein 2A (SV2A). In vitro and in vivo animal studies suggest faster brain penetration and SV2A occupancy (SO) after dosing with BRV than LEV. We evaluated human brain penetration and SO time course of BRV and LEV at therapeutically relevant doses using the SV2A positron emission tomography (PET) tracer 11C‐UCB‐J (; ). Methods Healthy volunteers were recruited into three cohorts. Cohort 1 (n = 4) was examined with PET at baseline and during displacement after intravenous BRV (100 mg) or LEV (1500 mg). Cohort 2 (n = 5) was studied during displacement and 4 hours postdose (BRV 50‐200 mg or LEV 1500 mg). Cohort 3 (n = 4) was examined at baseline and steady state after 4 days of twice‐daily oral dosing of BRV (50‐100 mg) and 4 hours postdose of LEV (250‐600 mg). Half‐time of 11C‐UCB‐J signal change was computed from displacement measurements. Half‐saturation concentrations (IC50) were determined from calculated SO. Results Observed tracer displacement half‐times were 18 ± 6 minutes for BRV (100 mg, n = 4), 9.7 and 10.1 minutes for BRV (200 mg, n = 2), and 28 ± 6 minutes for LEV (1500 mg, n = 6). Estimated corrected half‐times were 8 minutes shorter. The SO was 66%‐70% for 100 mg intravenous BRV, 84%‐85% for 200 mg intravenous BRV, and 78%‐84% for intravenous 1500 mg LEV. The IC50 of BRV (0.46 μg/mL) was 8.7‐fold lower than of LEV (4.02 μg/mL). BRV data fitted a single SO versus plasma concentration relationship. Steady state SO for 100 mg BRV was 86%‐87% (peak) and 76%‐82% (trough). Significance BRV achieves high SO more rapidly than LEV when intravenously administered at therapeutic doses. Thus, BRV may have utility in treating acute seizures; further clinical studies are needed for confirmation.

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Section: Discussionsupporting

confidence: 56%

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

et al. 2019

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“…13,14 On the other hand, postmarketing studies suggest a simple usage and favorable retention rates of the drug. A multicenter case series on the use of BRV in SE included 11 patients from two German hospitals and documented a treatment response in 27%.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…The median duration of SE before BRV administration was 5 days (range 1–16 days), and the median number of AEDs before initiation of BRV was 4 (range 1–6). Six patients had received levetiracetam before BRV . Three of 11 patients (27%) showed resolution of SE within 24 hours of initiation of BRV.…”

Section: Discussionmentioning

confidence: 99%

Use of Newer Anticonvulsants for the Treatment of Status Epilepticus

et al. 2019

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Status epilepticus (SE) has a high mortality rate and is one of the most common neurologic emergencies. Fast progression of this neurologic emergency and lack of response to traditional antiepileptic drugs (AEDs) in most cases has challenged clinicians to use new agents. This article evaluates the efficacy and safety of AEDs released to the market after 2000 for SE, refractory status epilepticus (RSE), and super‐refractory status epilepticus (SRSE). The PubMed database was searched for clinical trials published between January 2000 and July 2018 using the search terms status epilepticus, refractory status epilepticus, super refractory status epilepticus, brivaracetam, clobazam, cannabidiol, eslicarbazepine, lacosamide, perampanel, rufinamide, stiripentol, and zonisamide. Trials that evaluated these agents in adults with SE, RSE, and SRSE were included. Brivaracetam use was identified in two retrospective reviews with success rates of 27% and 57%. One unsuccessful case report of cannabidiol use in SE was found. Four clobazam studies were identified in SE and RSE with success rates ranging from 25–100%. No evidence for the use of eslicarbazepine and zonisamide was found. Using the search terms for lacosamide identified 38 articles: 1 systematic review, 5 prospective studies, 15 retrospective reviews, and 17 case reports. Success rates and dosing varied, but studies that included focal or partial types of SE showed higher success rates. Five articles were identified regarding perampanel use in this setting. Three were retrospective reviews with success rates ranging from 17–60%, and two were case reports. Only one case report regarding the use of rufinamide was found; rufinamide titrated up to 4.4 mg/day allowed discontinuation of barbiturate and clobazam. One case report and two case series of stiripentol were found with reported efficacy between 60% and 100% in SRSE. Evidence is currently insufficient to support the use of these agents in this setting.

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Treatment of refractory and super-refractory status epilepticus with brivaracetam: A cohort study from two German university hospitals

Cited by 72 publications

References 20 publications

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

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

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

Use of Newer Anticonvulsants for the Treatment of Status Epilepticus

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