Intravenous Brivaracetam in the Management of Acute Seizures in the Hospital Setting: A Scoping Review

Abstract

Background Clinical considerations for drug treatment of acute seizures involve variables such as safety, tolerability, drug-drug interactions, dosage, route of administration, and alterations in pharmacokinetics because of critical illness. Therapy options that are easily and quickly administered without dilution, well tolerated, and effective are needed for the treatment of acute seizures. The objective of this review is to focus on the clinical considerations relating to the use of intravenous brivaracetam (IV BRV) for the treatment of acute seizures in the hospital, focusing on critically ill patients. Methods This was a scoping literature review of PubMed from inception to April 13, 2021, and search of the American Academy of Neurology (AAN) 2021 Annual Meeting website for English language publications/conference abstracts reporting the results of IV BRV use in hospitalized patients, particularly in the critical care setting. Outcomes of interest relating to the clinical pharmacology, safety, tolerability, efficacy, and effectiveness of IV BRV were reviewed and are discussed. Results Twelve studies were included for analysis. One study showed that plasma concentrations of IV BRV 15 min after the first dose were similar between patients receiving IV BRV as bolus or infusion. IV BRV was generally well tolerated in patients with acute seizures in the hospital setting, with a low incidence of individual TEAEs classified as behavioral disorders. IV BRV demonstrated efficacy and effectiveness and had a rapid onset, with clinical and electrophysiological improvement in seizures observed within minutes. Although outside of the approved label, findings from several studies suggest that IV BRV reduces seizures and is generally well tolerated in patients with status epilepticus. Conclusions IV BRV shows effectiveness, and is generally well tolerated in the management of acute seizures in hospitalized patients where rapid administration is needed, representing a clinically relevant antiseizure medication for potential use in the critical care setting.

Diagnosing nonconvulsive status epilepticus: Defining electroencephalographic and clinical response to diagnostic intravenous antiseizure medication trials

“…16,17 However, in other studies, levetiracetam, lacosamide, and valproate were well tolerated at higher rates of administration and in higher doses. [18][19][20][21][22][23][24][25][26] The relatively high doses underscore the need of an "adequately high" first dose, which is approximately two thirds to three quarters of the full loading dose (exact mg/kg doses are presented in Table 2) used for treatment of convulsive SE to minimize the number of false negatives. Furthermore, the medication is also administered within a relatively short period of time to cause a high peak concentration in cerebrospinal fluid.…”

“…The doses recommended for levetiracetam and valproate are the same as those in prospective studies on SE 16,17 . However, in other studies, levetiracetam, lacosamide, and valproate were well tolerated at higher rates of administration and in higher doses 18–26 . The relatively high doses underscore the need of an “adequately high” first dose, which is approximately two thirds to three quarters of the full loading dose (exact mg/kg doses are presented in Table 2) used for treatment of convulsive SE to minimize the number of false negatives.…”

New Pharmacological Therapies in the Treatment of Epilepsy in the Pediatric Population

“…BRV is one of the substances that rapidly penetrates the blood–brain barrier, and its bioavailability is almost 100% [ 66 , 68 ]. The drug is metabolized in the liver with the involvement of CYP450, particularly CYP2C9 and CYP2C19 [ 69 , 70 ].…”

Recent advances in pharmacotherapy for epilepsy

“…Animal data suggests that brivaracetam may be effective in the treatment of refractory status epilepticus [32]. Several real-world experience studies of brivaracetam in refractory and super-refractory SE have shown SE cessation in approximately one-third of patients [37]. SE cessation is more likely with higher doses given early (e.g., 2 mg/kg initial dose) [37].…”

“…Several real-world experience studies of brivaracetam in refractory and super-refractory SE have shown SE cessation in approximately one-third of patients [37]. SE cessation is more likely with higher doses given early (e.g., 2 mg/kg initial dose) [37]. Animal data also suggest efficacy in IGE.…”