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Intravenous Brivaracetam in the Treatment of Status Epilepticus: A Systematic Review

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Abstract

Background

Brivaracetam is a high-affinity synaptic vesicle glycoprotein 2A ligand with high brain permeability and rapid onset of action. These properties make brivaracetam potentially an ideal compound in the emergency setting.

Objective

The objective of our study was to review the evidence about the clinical efficacy and tolerability of intravenous brivaracetam in the treatment of status epilepticus.

Methods

We systematically searched MEDLINE, EMBASE, Google Scholar, ClinicalTrials.gov, and conference proceedings to identify studies evaluating intravenous brivaracetam as treatment for status epilepticus of any type in patients of any age. Searches were conducted on 3 December, 2018.

Results

Seven studies were included (37 patients; aged 22–85 years; 21 were female). The type and etiology of status epilepticus varied across studies. The number of drugs used prior to brivaracetam to treat status epilepticus ranged from 1 to 8. The time from status epilepticus onset to brivaracetam administration ranged from 0.5 h to 105 days. The initial brivaracetam dose ranged from 50 to 400 mg. In case series, the proportion of patients achieving clinical status epilepticus cessation when brivaracetam was administered as the last drug varied from 27 to 50%; in case reports, all patients had status epilepticus cessation. The time from brivaracetam administration to status epilepticus cessation ranged from 15 min to 94 h. No serious adverse effects were reported.

Conclusions

The available data suggested that brivaracetam can be a safe treatment option in patients with status epilepticus. The current evidence is however hampered by several confounding factors, and controlled studies are warranted to define the actual benefit of brivaracetam for the treatment of status epilepticus.

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References

  1. Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus: report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56:1515–23.

    Article  PubMed  Google Scholar 

  2. Logroscino G, Hesdorffer DC, Cascino G, et al. Mortality after a first episode of status epilepticus in the United States and Europe. Epilepsia. 2005;46(Suppl. 11):46–8.

    Article  PubMed  Google Scholar 

  3. Leitinger M, Trinka E, Giovannini G, et al. Epidemiology of status epilepticus in adults: a population-based study on incidence, causes, and outcomes. Epilepsia. 2019;60:53–62.

    Article  PubMed  Google Scholar 

  4. Trinka E, Höfler J, Leitinger M, Brigo F. Pharmacotherapy for status epilepticus. Drugs. 2015;75:1499–521.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Trinka E, Höfler J, Leitinger M, et al. Pharmacologic treatment of status epilepticus. Expert Opin Pharmacother. 2016;17:513–34.

    Article  CAS  PubMed  Google Scholar 

  6. Brigo F, Bragazzi NL, Bacigaluppi S, et al. Is intravenous lorazepam really more effective and safe than intravenous diazepam as first-line treatment for convulsive status epilepticus? A systematic review with meta-analysis of randomized controlled trials. Epilepsy Behav. 2016;64:29–36.

    Article  PubMed  Google Scholar 

  7. Brigo F, Bragazzi NL, Lattanzi S, et al. A critical appraisal of randomized controlled trials on intravenous phenytoin in convulsive status epilepticus. Eur J Neurol. 2018;25:451–63.

    Article  CAS  PubMed  Google Scholar 

  8. US Food and Drug Administration. Brivaracetam, highlights of prescribing information, 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/205836s005,205837s004,205838s003lbl.pdf. Accessed 15 May 2019.

  9. Rolan P, Sargentini-Maier ML, Pigeolet E, et al. The pharmacokinetics, CNS pharmacodynamics and adverse event profile of brivaracetam after multiple increasing oral doses in healthy men. Br J Clin Pharmacol. 2008;66:71–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sargentini-Maier ML, Espie P, Coquette A, et al. Pharmacokinetics and metabolism of 14C-brivaracetam, a novel SV2A ligand, in healthy subjects. Drug Metab Dispos. 2008;36:36–45.

    Article  CAS  PubMed  Google Scholar 

  11. Strzelczyk A, Klein KM, Willems LM, et al. Brivaracetam in the treatment of focal and idiopathic generalized epilepsies and of status epilepticus. Expert Rev Clin Pharmacol. 2016;9:637–45.

    Article  CAS  PubMed  Google Scholar 

  12. Nicolas JM, Hannestad J, Holden D, et al. Brivaracetam, a selective high-affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia. 2016;57:201–9.

    Article  CAS  PubMed  Google Scholar 

  13. Finnema SJ, Rossano S, Naganawa M, et al. A single-center, open-label positron emission tomography study to evaluate brivaracetam and levetiracetam synaptic vesicle glycoprotein 2A binding in healthy volunteers. Epilepsia. 2019;60:958–67.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Wasterlain CG, Suchomelova L, Matagne A, et al. Brivaracetam is a potent anticonvulsant in experimental status epilepticus. Epilepsia. 2005;46(Suppl. 8):219.

    Google Scholar 

  15. Hutton B, Salanti G, Caldwell DM, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162:777–84.

    Article  PubMed  Google Scholar 

  16. Beier CP, Blaabjerg M. Successful treatment of status epilepticus with brivaracetam. In: American Epilepsy Society Annual Meeting; 2–6 Dec, 2016; Houston (TX): abstract no. 1.193.

  17. Fleming D, Clayton SM, Ray B. Posterior reversible encephalopathy syndrome and refractory status epilepticus treated with ketamine and brivaracetam. Neurocrit Care. 2017;27(Suppl. 1):S448.

    Google Scholar 

  18. Strzelczyk A, Steinig I, Willems LM, et al. Treatment of refractory and super-refractory status epilepticus with brivaracetam: a cohort study from two German university hospitals. Epilepsy Behav. 2017;70:177–81.

    Article  PubMed  Google Scholar 

  19. Strzelczyk A, Kay L, Bauer S, et al. Use of brivaracetam in genetic generalized epilepsies and for acute, intravenous treatment of absence status epilepticus. Epilepsia. 2018;59:1549–56.

    Article  CAS  PubMed  Google Scholar 

  20. Manacheril R, Khan FA, Steven A, et al. Focal status epilepticus in a patient with stroke like migraine attacks after radiation therapy (SMART) syndrome. Clin Neurophysiol. 2018;129(Suppl. 1):e74.

    Article  Google Scholar 

  21. Kalss G, Rohracher A, Leitinger M, et al. Intravenous brivaracetam in status epilepticus: a retrospective single-center study. Epilepsia. 2018;59(Suppl. 2):228–33.

    Article  CAS  PubMed  Google Scholar 

  22. Aicua-Rapun I, André P, Rossetti AO, et al. Intravenous brivaracetam in status epilepticus: correlation between loading dose, plasma levels and clinical response. Epilepsy Res. 2019;149:88–91.

    Article  CAS  PubMed  Google Scholar 

  23. McGauran N, Wieseler B, Kreis J, et al. Reporting bias in medical research: a narrative review. Trials. 2010;11:37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rossetti AO, Alvarez V, Januel JM, Burnand B. Treatment deviating from guidelines does not influence status epilepticus prognosis. J Neurol. 2013;260:421–8.

    Article  PubMed  Google Scholar 

  25. Perrenoud M, André P, Alvarez V, et al. Intravenous lacosamide in status epilepticus: correlation between loading dose, serum levels, and clinical response. Epilepsy Res. 2017;135:38–42.

    Article  CAS  PubMed  Google Scholar 

  26. Paulson OB, Gyory A, Hertz MM. Blood–brain barrier transfer and cerebral uptake of antiepileptic drugs. Clin Pharmacol Ther. 1982;32:466–77.

    Article  CAS  PubMed  Google Scholar 

  27. Niquet J, Suchomelova L, Thompson K, et al. Acute and long-term effects of brivaracetam and brivaracetam-diazepam combinations in an experimental model of status epilepticus. Epilepsia. 2017;58:1199–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Brigo F, Bragazzi N, Nardone R, Trinka E. Direct and indirect comparison meta-analysis of levetiracetam versus phenytoin or valproate for convulsive status epilepticus. Epilepsy Behav. 2016;64:110–5.

    Article  PubMed  Google Scholar 

  29. Navarro V, Dagron C, Elie C, SAMUKeppra Investigators, et al. Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial. Lancet Neurol. 2016;15:47–55.

    Article  CAS  PubMed  Google Scholar 

  30. Schomer AC, Kapur J. The SAMUKeppra study in prehospital status epilepticus: lessons for future study. Ann Transl Med. 2016;4:468.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kellinghaus C, Rossetti AO, Trinka E, et al. SENSE registry for status epilepticus. Epilepsia. 2018;59:150–4.

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. Francesco Brigo and Simona Lattanzi contributed equally.

Authors and Affiliations

  1. Division of Neurology, “Franz Tappeiner” Hospital, Merano, Bolzano, Italy

    Francesco Brigo & Raffaele Nardone

  2. Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy

    Francesco Brigo

  3. Department of Experimental and Clinical Medicine, Neurological Clinic, Marche Polytechnic University, Ancona, Italy

    Simona Lattanzi

  4. Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria

    Raffaele Nardone & Eugen Trinka

  5. Institute of Public Health, Medical Decision Making and Health Technology Assessment, University for Health Sciences, Medical Informatics and Technology, UMIT, Hall in Tyrol, Austria

    Eugen Trinka

Authors
  1. Francesco Brigo
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  2. Simona Lattanzi
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  4. Eugen Trinka
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Corresponding author

Correspondence to Francesco Brigo.

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Funding

No funding was received for the conduct of this study or the preparation of this article.

Conflict of interest

Francesco Brigo has acted as a paid consultant to Eisai and LivaNova, and received travel support from Eisai. Eugen Trinka has acted as a paid consultant to Eisai, EVER Neuro Pharma, Biogen Idec, Medtronics, Bial, and UCB and has received speakers’ honoraria from Bial, Eisai, Boehringer Ingelheim, Biogen, Newbridge, Novartis, and UCB Pharma in the past 3 years. Eugen Trinka has received research funding from UCB Pharma, Biogen, Novartis, Bayer, Eisai, Red Bull, Merck, the European Union, FWF Österreichischer Fond zur Wissenschaftsförderung, and Bundesministerium für Wissenschaft und Forschung. Eugen Trinka is also part of the investigators planning the ESET Trial and a member of the Task Force on Classification of Status Epilepticus of the International League Against Epilepsy. Simona Lattanzi and Raffaele Nardone have no conflicts of interest that are directly relevant to the content of this article.

Ethical Approval

This is a systematic review of the literature, and not an original research study involving human participants and/or animals.

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Brigo, F., Lattanzi, S., Nardone, R. et al. Intravenous Brivaracetam in the Treatment of Status Epilepticus: A Systematic Review. CNS Drugs 33, 771–781 (2019). https://doi.org/10.1007/s40263-019-00652-0

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  • DOI: https://doi.org/10.1007/s40263-019-00652-0

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