By: Aya Alrmah
This article is meant for educational purposes only and should not be taken as direct medical advice. For any questions or concerns, please speak to your healthcare provider.
Traditional anticonvulsant drugs have been used for decades to manage epilepsy, but their low safety margins and poor selectivity have driven the search for safer alternatives. Brivaracetam, also known as Briviact, is a third-generation anticonvulsant with improved tolerability and safety compared to first-generation drugs, such as Phenytoin and Carbamazepine (Moseley et al., 2020). It is approved for treating partial-onset seizures in patients as young as one month old (U.S. Food and Drug Administration, 2016). Brivaracetam is an analogue of Levetiracetam and shares a similar mechanism of action. It binds to synaptic vesicle protein 2A (SV2A), a key regulator of neurotransmitter release, enhancing its anticonvulsant effect. Both brivaracetam and levetiracetam offer significant therapeutic benefits, but brivaracetam is associated with fewer behavioral side effects than levetiracetam.
Brivaracetam is available in three dosage forms: tablets, injections, and an oral solution. The tablet strengths include 10 mg, 25 mg, 50 mg, 75 mg, and 100 mg per tablet. The injectable form is available as a 50 mg/5 mL solution, administered as a single dose. The oral solution is supplied at a concentration of 10 mg/mL. For patients aged 16 and older, the recommended starting dose is 100 mg per day, which can be adjusted between 50 mg and 200 mg daily based on individual tolerability. In patients younger than 16, the dosage is determined based on body weight and administered orally. If oral administration is not feasible, the injectable form may be used as an alternative, (U.S. Food and Drug Administration, 2016).
Brivaracetam has relatively few drug-drug interactions, making it more favorable compared to many other anticonvulsants. This advantage stems from brivaracetam’s minimal interaction with most metabolic enzymes and drug transporters utilized by other medications. However, dose adjustments are necessary when brivaracetam is co-administered with certain metabolic enzyme inducers, such as rifampin and St. John’s wort (Moseley et al., 2020). The U.S. Food and Drug Administration (FDA) recommends doubling the brivaracetam dose when used alongside rifampin.
By binding to synaptic vessel protein 2A (SV2A), brivaracetam is able to reduce the frequency of seizures in patients. This protein plays an important role in regulating neurotransmitter release, and its function is hindered once brivaracetam binds to it. Although brivaracetam shares a mechanism of action with levetiracetam, brivaracetam has a higher affinity and more rapid brain permeability compared to levetiracetam, (Amengual-Gual, 2019).
Once brivaracetam (BRV) enters the body, it undergoes four main pharmacokinetic processes: absorption, distribution, metabolism, and excretion. This anticonvulsant is rapidly absorbed into the bloodstream, reaching peak plasma concentration within an hour. However, due to brivaracetam’s lipid-soluble nature, peak plasma concentrations are delayed to approximately three hours when consumed with high-fat meals. This lipophilicity allows BRV to rapidly diffuse across the blood-brain barrier and reach its target sites, enhancing its effectiveness compared to levetiracetam (LEV). After exerting its therapeutic effect, BRV undergoes extensive metabolism, primarily through hydrolysis, where a water molecule is added to form an inactive metabolite. These metabolites are excreted via the urine, with over 95% eliminated within 72 hours, (Klein etal., 2018) .
As with all medications, adverse reactions may occur. Common side effects include anxiety, decreased appetite, constipation, cough, depression, dizziness, drowsiness, fatigue, increased infection risk, insomnia, irritability, nausea, vertigo, and vomiting. Less commonly, behavioral changes such as suicidal ideation and psychotic disorders may occur. This is not an exhaustive list of side effects, so consulting reputable sources like the British National Formulary (BNF) and the FDA is recommended. If side effects persist or worsen, seek medical advice promptly, (Joint Formulary Committee, n.d.).
Brivaracetam represents a significant advancement in epilepsy treatment, offering improved tolerability and safety compared to earlier anticonvulsants. Its high selectivity for SV2A, minimal drug interactions, and favorable pharmacokinetic profile contribute to its therapeutic advantages over first-generation AEDs. While brivaracetam is generally well-tolerated, potential side effects and the need for dose adjustments in certain cases should be carefully considered. As research continues to explore novel antiepileptic therapies, brivaracetam remains a valuable option for managing partial-onset seizures, providing patients with a more effective and safer alternative to traditional treatments.
References
- Brian D. Moseley, Hugues Chanteux, Jean-Marie Nicolas, Cédric Laloyaux, Barry Gidal, Armel Stockis, A review of the drug−drug interactions of the antiepileptic drug brivaracetam, Epilepsy Research, Volume 163, 2020, 106327, ISSN 0920-1211, https://doi.org/10.1016/j.eplepsyres.2020.106327.
- U.S. Food and Drug Administration, 2016, Briviact (brivaracetam) Label, https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/205836s009,205837s007,205838s006lbl.pdf
- Marta Amengual-Gual, Iván Sánchez Fernández, Mark S. Wainwright, Novel drugs and early polypharmacotherapy in status epilepticus, Seizure, Volume 68, 2019, Pages 79-88, ISSN 1059-1311, https://doi.org/10.1016/j.seizure.2018.08.004.
- Klein P, Diaz A, Gasalla T, Whitesides J. A review of the pharmacology and clinical efficacy of brivaracetam. Clin Pharmacol. 2018 Jan 19;10:1-22. doi: 10.2147/CPAA.S114072. PMID: 29403319; PMCID: PMC5783144.
- Joint Formulary Committee. (n.d.). British National Formulary (BNF), BMJ Group and Pharmaceutical Press, https://bnf.nice.org.uk/drugs/brivaracetam/#side-effects
