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Brivaracetam
Clinical data
Pronunciation/ˌbrɪvəˈræsətəm/ BRIV-ə-RASS-ə-təm
Trade namesBriviact, Nubriveo, Brivajoy
AHFS/Drugs.comMonograph
MedlinePlusa616027
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityNearly 100%
Protein binding≤20%
MetabolismHydrolysis by amidase, CYP2C19-mediated hydroxylation
Metabolites3 inactive metabolites
Elimination half-life≈9 hours
ExcretionKidneys (>95%)[4]
Identifiers
  • (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl] butanamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.118.642 Edit this at Wikidata
Chemical and physical data
FormulaC11H20N2O2
Molar mass212.293 g·mol−1
3D model (JSmol)
Specific rotation[α]D −60°
Melting point72 to 77 °C (162 to 171 °F)
  • O=C(N)[C@@H](N1C(=O)C[C@@H](CCC)C1)CC
  • InChI=1S/C11H20N2O2/c1-3-5-8-6-10(14)13(7-8)9(4-2)11(12)15/h8-9H,3-7H2,1-2H3,(H2,12,15)/t8-,9+/m1/s1 checkY
  • Key:MSYKRHVOOPPJKU-BDAKNGLRSA-N checkY

Brivaracetam, sold under the brand name Briviact among others, is a chemical analog of levetiracetam, a racetam derivative with anticonvulsant (antiepileptic) properties.[5][6] It has been approved since 2016. It is marketed by the pharmaceutical company UCB.[7][8] It is used to treat partial-onset seizures with or without secondary generalisation, in combination with other antiepileptic drugs.

Medical uses

[edit]

Brivaracetam is used to treat partial-onset seizures with or without secondary generalisation, in combination with other antiepileptic drugs. Efficacy and tolerability is comparable in general and Intellectual Disability populations.[9] No data are available for its effectiveness and safety in people younger than 16 years of age.[10][11][12]

Adverse effects

[edit]

The most common adverse effects include sleepiness, dizziness, nausea and vomiting. More rarely, coordination problems and changes in behaviour (such as severe depression, aggression, hostility, impatience, rage, suicidal ideation, etc.) can occur.[10][11]

No clinically relevant differences in adverse effects incidence for the starting doses were observed, except for a dose–response relationship for somnolence and fatigue.[13]

Interactions

[edit]

Coadministration of brivaracetam with carbamazepine may increase exposure to carbamazepine-epoxide, the active metabolite of carbamazepine, and could theoretically lead to reduced tolerability. Coadministration of brivaracetam with phenytoin may increase phenytoin levels. Coadministration of other antiseizure drugs are unlikely to affect brivaracetam exposure. Brivaracetam provides no added therapeutic benefit when administered in conjunction with levetiracetam that acts on the same protein.[14]

No pharmacokinetic interaction was observed between single-dose 200mg brivaracetam and 0.6g/L ethanol in healthy subjects. However, brivaracetam approximately doubled the effect of alcohol on psychomotor function, attention and memory. Alcohol use while under brivaracetam treatment is not recommended.[11]

Pharmacology

[edit]

Mechanism of action

[edit]

Brivaracetam is believed to act by binding to the ubiquitous synaptic vesicle glycoprotein 2A (SV2A), like levetiracetam, but with 20-fold greater affinity.[15][16] There is some evidence that racetams including levetiracetam and brivaracetam access the luminal side of recycling synaptic vesicles during vesicular endocytosis. They may reduce excitatory neurotransmitter release and enhance synaptic depression during trains of high-frequency activity, such as is believed to occur during epileptic activity.[17]

Pharmacokinetics

[edit]

Brivaracetam exhibits linear pharmacokinetics over a wide dose range, is rapidly and completely absorbed after oral administration, has an elimination half-life of seven to eight hours, and has plasma protein binding of less than 20%. It is extensively metabolized (>90%), primarily via hydrolysis of the acetamide group, and secondarily through hydroxylation mediated by the liver enzyme CYP2C19. The three major metabolites (hydroxy, acid, and hydroxyacid) are pharmacologically inactive. Brivaracetam is eliminated as urinary metabolites, with over 95% of a radioactive test dose recovered in the urine within 72 hours, including only 8.6% as unchanged brivaracetam.[18]

Brivaracetam can be interchanged with levetiracetam as follows: 50 mg Brivaracetam by 1,000 mg levetiracetam, 100 mg of brivaracetam by 2,000 mg levetiracetam, and 200 mg of brivaracetam by 3,000 mg levetiracetam.[19]

Pharmacogenetics

[edit]

As noted above, brivaracetam is primarily metabolized by hydrolysis, via amidase enzymes, to an inactive metabolite. To a lesser extent, it is also metabolized by a minor metabolic pathway via CYP2C19-dependent hydroxylation. Individuals who have no CYP2C19 enzyme activity, "CYP2C19 poor metabolizers", will have a greater exposure to standard doses of brivaracetam. Because they are less able to metabolize the drug to its inactive form for excretion, they may have an increased risk of adverse effects. The most common adverse effects of brivaracetam therapy include sedation, fatigue, dizziness, and nausea.[20] The FDA-approved drug label for brivaracetam states that patients who are CYPC19 poor metabolizers, or are taking medicines that inhibit CYP2C19, may require a dose reduction.[4]

Chemical and physical properties

[edit]
Levetiracetam, for comparison

Brivaracetam is the 4R-propyl analogue of the anticonvulsant levetiracetam.

History

[edit]

Positive preliminary results from stage III trials were recorded in 2008,[21] along with evidence that it is around ten times more potent for the prevention of certain types of seizure in mouse models than its analogue levetiracetam.[22]

On 14 January 2016, the European Commission,[11] and on 18 February 2016, the U.S. Food and Drug Administration (FDA)[23] approved brivaracetam under the trade name Briviact. The Drug Enforcement Administration (DEA) issued an interim final rule[clarification needed] placing brivaracetam into schedule V of the Controlled Substances Act (CSA) effective 9 March 2017.[24] As of May 2016, brivaracetam is not approved in some other countries. It was approved in Australia in August 2016.[25]

In Canada it was approved on 9 March 2016 under the trade name Brivlera.[26]

Society and culture

[edit]

As of 2022, the US Food and Drug Administration approved a generic drug version of brivaracetam, but as of 2023 it was not yet available as a generic medication.[27][28]

In Argentina, brivaracetam has been sold under the brand Brivaxon from Raffo Laboratories and Briviact from Biopas Argentina.[29][30]

In Germany, UCB was unable to demonstrate an additional benefit in 2016,[31] 2018[32] and 2022[33] by adding brivaracetam. In Germany, newly approved drugs with new active ingredients have to be evaluated by the Federal Joint Committee (Germany)(Gemeinsamer Bundesausschuss) if the pharmaceutical manufacturer wishes to achieve a higher selling price than just the fixed amount. Only if there is an additional benefit, the pharmaceutical manufacturer can negotiate a price with the top association of statutory health insurance companies.

References

[edit]

Further reading

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Brivaracetam

View on Grokipedia
from Grokipedia
Brivaracetam, sold under the brand name Briviact among others, is a rationally designed medication approved as adjunctive for partial-onset seizures in patients with aged 1 month and older. It functions primarily by binding with high affinity to synaptic vesicle glycoprotein 2A () in the , a mechanism shared with but more potent than that of , its structural analog in the class. Developed by the pharmaceutical company UCB, brivaracetam is available in oral tablet, oral solution, and intravenous formulations, offering flexibility for clinical use. The drug was approved by the (EMA) on January 14, 2016, and by the U.S. (FDA) on February 18, 2016, for patients aged 16 years and older. In August 2021, the FDA expanded approval to include pediatric patients as young as 1 month, based on pharmacokinetic data, safety profiles from adult trials, and supportive studies in children. Brivaracetam exhibits nearly 100% oral , rapid absorption with peak plasma concentrations within 1 hour, and a plasma half-life of approximately 7-8 hours, primarily metabolized via non-cytochrome P450 and excreted renally. Clinical efficacy has been demonstrated in randomized, placebo-controlled trials, showing significant reductions in frequency as an add-on therapy when conventional antiepileptic drugs are inadequate. Common adverse effects include , , , and , with a risk of psychiatric symptoms, reactions, and observed across age groups. As a Schedule V in the U.S., brivaracetam carries a low potential for abuse and dependence, though abrupt discontinuation may precipitate . Ongoing research continues to explore its role in broader management and potential off-label applications.

Medical Applications

Indications

Brivaracetam is approved by the (FDA) as monotherapy or adjunctive for partial-onset (focal) seizures in patients aged 1 month and older. This approval stems from evidence establishing its antiseizure effects through high-affinity binding to protein 2A (). Pivotal phase III clinical trials (N01194, N01252, and N01255) in adults with partial-onset s demonstrated the of adjunctive brivaracetam at doses of 50–200 mg/day, with 50% responder rates (≥50% reduction in frequency) ranging from 39% to 50%, compared to 17–22% for . These trials involved over 1,500 patients and showed median percent reductions in weekly frequency of 18–29% over , targeting adults with at least eight partial-onset s during an 8-week baseline period despite ongoing antiepileptic . The FDA expanded approval to pediatric patients in August 2021, based on pharmacokinetic bridging studies demonstrating similar drug exposure across age groups and long-term safety data from open-label extension studies involving children aged 1 month to less than 16 years. Efficacy in is extrapolated from adult trials, with observational data indicating comparable 50% responder rates of approximately 40–45% in children with partial-onset seizures. While primarily indicated for focal seizures, recent 2025 studies have suggested potential in primary generalized seizures, with adjunctive brivaracetam showing freedom in up to 20% of pediatric patients and significant frequency reductions in broader cohorts.

Dosage and Administration

Brivaracetam is administered orally or intravenously for the treatment of partial-onset seizures in patients aged 1 month and older. For adults and adolescents weighing 50 kg or more, the recommended starting dose is 50 mg twice daily, with maintenance doses ranging from 25 mg to 100 mg twice daily based on individual tolerability and response; no gradual is required. In pediatric patients aged 1 month to less than 16 years, dosing is weight-based and divided into twice-daily administration, starting at 1 to 2 mg/kg/day (for example, 0.5 to 1 mg/kg twice daily), and may be adjusted up to a maximum of 5 mg/kg/day depending on body weight category (e.g., up to 2.5 mg/kg twice daily for patients 11 to less than 20 kg). Dose adjustments are recommended for hepatic impairment: in adults, start at 25 mg twice daily with a maximum of 75 mg twice daily; in , maximum doses are reduced (e.g., 2 mg/kg twice daily for patients under 20 kg). No dose adjustment is needed for renal impairment, though use is not recommended in end-stage renal disease patients undergoing dialysis. Brivaracetam is available in oral tablet, oral solution, and intravenous injection formulations. Tablets should be swallowed whole with liquid and can be taken with or without food; the oral solution requires a calibrated measuring device and may be given via nasogastric or tube, with the bottle discarded after 5 months once opened. Intravenous administration uses the same milligram dosage as the oral regimen, infused over 2 to 15 minutes, either undiluted or diluted in compatible solutions such as 0.9% or 5% dextrose; no dose conversion is necessary when switching routes, and the injection is for short-term use when is not feasible. Abrupt discontinuation should be avoided to prevent increased frequency; gradual withdrawal is advised. Plasma level monitoring is not routinely required for brivaracetam therapy, but if performed, a therapeutic range of approximately 0.1 to 2.0 mg/L may guide adjustments in select cases.

Safety Profile

Adverse Effects

The most common adverse effects associated with brivaracetam, observed in more than 10% of patients in controlled clinical trials, include or sedation (16%), (12%), and (9%), with occurring in 5-7% of patients receiving doses of 50 mg/day or higher. These effects were reported in pooled data from phase 3 adjunctive therapy trials (N01252, N01253, and N01358), where overall adverse events occurred in 68% of brivaracetam-treated patients compared to 62% on , leading to discontinuation in 7% versus 4%, respectively. and typically emerge early in treatment and may impair coordination, necessitating warnings against driving or operating machinery until effects are known. Serious adverse effects include psychiatric reactions such as , anxiety, , and depression, affecting 5-13% of patients (13% overall versus 8% on ), with 1.7% discontinuing due to these issues. Hematologic abnormalities, including decreases in count, count, and platelets, have been reported; monitoring may be appropriate in patients with baseline abnormalities. Brivaracetam carries a warning for and , with an incidence of 0.43% across antiepileptic drugs like brivaracetam compared to 0.24% for , approximately doubling the risk ( 1.8). In August 2025, the FDA updated the labeling to include warnings for serious dermatologic reactions, including Stevens-Johnson syndrome and , with onset ranging from 3 to 45 days; immediate discontinuation is required upon onset. In pediatric patients (aged 2 months to less than 16 years), adverse effects mirror those in adults, but decreased and irritability are more prominent, occurring in up to 10% and 7% of cases, respectively, in open-label studies. Long-term data from extension trials indicate high retention rates (over 50% at 5 years) and suggest behavioral functioning is generally stable or improved in some cohorts, with treatment-emergent psychiatric events resolving without dose change in most cases. Management of adverse effects involves close monitoring for emergence of symptoms, with dose reduction considered for mild to moderate cases like or psychiatric reactions to improve tolerability, while severe effects such as , , or dermatologic reactions require immediate discontinuation and medical evaluation. Gradual tapering over at least one week is recommended to minimize exacerbation upon withdrawal. Concomitant use with other depressants may exacerbate sedation and .

Contraindications and Precautions

Brivaracetam is contraindicated in patients with a known to the drug or to other pyrrolidone derivatives such as , as well as to any of its excipients, due to the risk of serious allergic reactions including and . In , animal reproduction studies have shown developmental toxicity at exposures greater than clinical exposure, but there are no adequate data in pregnant women on risks to the ; use during only if the potential benefit justifies the potential risk to the . Enrollment in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334 or http://www.aedpregnancyregistry.org/) is recommended to monitor outcomes. During , brivaracetam is excreted into human milk, though the clinical significance is unknown; a decision should be made whether to discontinue or the drug, considering the importance of the medication to the mother. Caution is advised in elderly patients due to potential declines in organ function, greater sensitivity to drug effects, and limited clinical data; dose selection should be cautious, generally starting at the low end of the dosing range. In patients with a history of psychiatric disorders, brivaracetam requires close monitoring for worsening symptoms, including , depression, aggression, anxiety, or , as these have been reported in association with its use. No dose adjustment is required for patients with renal impairment, including those with clearance as low as 30 mL/min, though use is not recommended in end-stage renal disease patients undergoing dialysis due to lack of data. For hepatic impairment, dose reduction is necessary: in mild impairment (Child-Pugh A), the maximum dose is 150 mg/day; in moderate (Child-Pugh B) or severe (Child-Pugh C), the starting dose is 50 mg/day with a maximum of 150 mg/day for adults, with proportional adjustments for pediatric patients based on body weight. Treatment should be discontinued immediately if a rash suggestive of Stevens-Johnson syndrome or develops, as severe cutaneous adverse reactions have been reported. Due to potential central nervous system effects such as , , and —which may contribute to impaired coordination—patients should be advised not to drive or operate hazardous machinery until they have gained sufficient experience with the 's effects under stable conditions.

Drug Interactions

Pharmacokinetic Interactions

Brivaracetam exhibits a low potential for pharmacokinetic interactions due to its primary via non-cytochrome P450 (CYP) and minimal involvement in CYP pathways. It acts as a weak inhibitor of , which can modestly elevate levels of CYP2C19 substrates. For instance, co-administration with results in increased exposure to the carbamazepine-epoxide by 37% at 50 mg/day, 62% at 100 mg/day, and 98% at 200 mg/day of brivaracetam, though no dose adjustments are typically required unless tolerability issues arise. Brivaracetam does not significantly induce or inhibit , as evidenced by no change in exposure following brivaracetam administration at therapeutic doses. Several drugs can alter brivaracetam , primarily through induction of its metabolic pathways. Rifampin, a potent inducer of and , decreases brivaracetam area under the curve (AUC) by approximately 45%, necessitating a dose increase of up to 100 mg/day when co-administered and subsequent adjustment upon discontinuation. In contrast, reduces brivaracetam AUC by 26-29% and maximum concentration (Cmax) by 13% due to mild induction, but no dose adjustment is recommended. has no significant effect on brivaracetam . A case series reported interactions with cannabidiol (CBD), which inhibits and can substantially increase brivaracetam serum levels. In patients on adjunctive CBD therapy, brivaracetam concentrations rose by 95% to 280%, potentially requiring dose reductions to prevent toxicity. Brivaracetam's low (≤20%) minimizes risks of displacement interactions with highly bound drugs. Overall, these interactions are generally manageable with monitoring or minor dose adjustments.

Clinical Interactions

Brivaracetam exhibits additive (CNS) depression when co-administered with other antiepileptic drugs (AEDs) such as or , which can manifest as increased , , and psychomotor impairment. Specifically, brivaracetam can elevate plasma concentrations by approximately 20% at supratherapeutic doses, though clinically relevant increases are less likely at standard doses; monitoring of levels is recommended, with dose adjustments if elevations exceed 10%. In contrast, combining brivaracetam with yields no additional therapeutic benefit in control. Co-administration of brivaracetam with alcohol or medications intensifies CNS effects, including enhanced , impaired coordination, reduced , and deficits, thereby increasing the risk of falls and accidents; patients are advised to avoid or limit alcohol and use caution with sedatives. When brivaracetam is used concurrently with antidepressants, particularly those with CNS-depressant properties like tricyclics, there is potential for additive effects such as drowsiness, , and ; clinical monitoring for psychiatric worsening, including mood changes or behavioral alterations, is essential. Herbal supplements like St. John's wort may reduce brivaracetam efficacy through induction of its metabolism, similar to the effect of rifampin, which necessitates caution, potential dose doubling, and close monitoring of seizure control.

Pharmacology

Mechanism of Action

Brivaracetam exerts its antiseizure effects primarily through high-affinity binding to the synaptic vesicle 2A () protein, a ubiquitous transmembrane located on the membranes of synaptic vesicles in neurons and neuroendocrine cells. This binding is characterized by a (Kd) of approximately 0.5 nM in membranes and 0.08 nM in cortical membranes, demonstrating saturable, reversible, and specific interaction. Compared to , another SV2A ligand, brivaracetam exhibits 15- to 30-fold higher affinity for SV2A, enabling more potent modulation at lower concentrations. The SV2A protein plays a critical role in the regulation of vesicular trafficking and , though the exact downstream pathways linking SV2A occupancy to antiseizure activity remain incompletely elucidated. A 2024 cryo-electron microscopy study has elucidated the atomic of the SV2A-brivaracetam complex, revealing that brivaracetam binds in a central transmembrane cavity, interacting with key residues such as Trp300 and Trp666, providing insights into its high-affinity binding mode. Brivaracetam demonstrates high selectivity for , with negligible affinity for the related isoform SV2B, as it fails to displace radiolabeled ligands from SV2B at concentrations up to 10 μM. Furthermore, brivaracetam shows no significant binding to other major neuronal targets, including voltage-gated sodium channels, GABA or glutamate receptors, or high-voltage-activated calcium channels, distinguishing it from broader-spectrum antiepileptics. This targeted profile minimizes off-target effects and contributes to its favorable in preclinical assessments. At the synaptic level, brivaracetam modulates release by binding to , which inhibits excessive of excitatory neurotransmitters such as glutamate from presynaptic terminals and astroglial cells, thereby reducing hyperexcitability in epileptic circuits. Concurrently, it indirectly enhances inhibitory transmission without direct at GABA receptors, potentially by counteracting zinc-mediated inhibition of GABA and receptors at concentrations 10- to 30-fold lower than . These effects normalize the balance between excitation and inhibition in seizure-prone networks. Preclinical studies in animal models of , including audiogenic -prone mice and kindling paradigms, have established a strong inverse correlation between occupancy by brivaracetam and frequency, with higher binding saturation linked to greater efficacy across various epileptogenic challenges. This relationship underscores as the primary molecular target underpinning brivaracetam's antiseizure potency.

Pharmacokinetics

Brivaracetam exhibits rapid absorption following , with nearly complete of approximately 100%. Peak plasma concentrations are typically reached within 0.5 to 2 hours (median Tmax around 1 hour), and food has minimal impact on overall , though a high-fat may slightly reduce Cmax by about 37% and delay Tmax without significantly affecting AUC. The drug distributes widely in the body, with a of approximately 0.5 L/kg, indicating distribution primarily into total body water. Brivaracetam demonstrates low of less than 20%, which contributes to its favorable distribution profile, including efficient penetration across the blood-brain barrier to reach its target. Metabolism of brivaracetam occurs primarily through non-cytochrome P450 mediated by amidases to an inactive metabolite, accounting for about 50% of the dose. A secondary pathway involves mediated by , representing a minor portion (around 20%), with no pharmacologically active metabolites produced. The elimination is 7 to 9 hours, supporting twice-daily dosing. Excretion is predominantly renal, with over 95% of the dose recovered in within 72 hours and less than 10% excreted as unchanged drug. Less than 1% is eliminated in . While renal clearance is reduced in patients with impaired renal function, dose adjustments are not required for mild to severe impairment, though use is not recommended in end-stage renal disease undergoing dialysis due to limited data.

Pharmacogenetics

Brivaracetam, an antiseizure medication primarily metabolized through , exhibits pharmacogenetic variability mainly influenced by polymorphisms in the gene, which contributes to a minor pathway. Genetic variations in can alter drug exposure and potentially affect tolerability, though routine pharmacogenetic testing is not recommended due to the drug's predominant non-CYP . Individuals with poor metabolizer phenotypes, such as those carrying two nonfunctional like *2/*2, *2/*3, or *3/*3, experience approximately 42% higher plasma exposure to brivaracetam compared to normal metabolizers, along with a 10-fold reduction in the formation of the hydroxy . Intermediate metabolizers, with one nonfunctional (e.g., *1/*2 or *1/*3), show about 22% increased exposure and twofold reduced production. These variants are more prevalent in certain populations, such as 14% of Chinese individuals carrying poor metabolizer . Clinical guidelines suggest considering dose reductions in poor metabolizers to mitigate risks of adverse effects like or , and pharmacogenetic testing for *2, *3, and *17 may be useful in cases of non-response or intolerance. Polymorphisms in the gene, the primary target of brivaracetam, have been investigated for their potential role in efficacy variability, but studies indicate no significant association with treatment response, similar to findings for the related levetiracetam. Emerging data suggest possible subtle influences on antiseizure effects, yet these are not clinically actionable at present. Evidence for major impacts from other genes, such as those encoding UDP-glucuronosyltransferases (UGT) or additional antiseizure medication-related loci, remains limited, with no established associations affecting brivaracetam metabolism or response.

Chemistry and Properties

Chemical Structure

Brivaracetam is a chiral with the IUPAC name (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yl]butanamide and the molecular C₁₁H₂₀N₂O₂, corresponding to a molecular weight of 212.29 g/mol. Its core structure features a pyrrolidinone ring substituted at the 1-position with a butanamide chain bearing an (S)-configuration at the alpha carbon (C2), and at the 4-position with a in the (R)-configuration. This arrangement defines the two stereocenters essential to its identity. As a of , brivaracetam differs primarily by the incorporation of a propyl at the 4-position of the pyrrolidinone ring, which imparts enhanced affinity for protein 2A () compared to its predecessor. The active is specifically the (2S,4R) . The synthesis of brivaracetam involves a multi-step process starting from a pyrrolidone core, typically proceeding through formation of the substituted pyrrolidinone intermediate followed by coupling with the chiral butanamide moiety. is employed to isolate the desired (S)-configuration at C2 and (R)-configuration at C4, often via techniques such as chiral HPLC or enzymatic resolution of racemic precursors. This stereoselective approach ensures the production of the bioactive (2S,4R) in high purity.

Physical Properties

Brivaracetam is a white to off-white crystalline powder. It exhibits high aqueous , with approximately 850 mg/mL in at 7.4 and 37°C, and is very soluble in , , and buffers across a range of values (1.2 to 7.4). The compound is freely soluble in and acetone, soluble in , and very slightly soluble in n-hexane. This profile, influenced by its pyrrolidone-based , facilitates its formulation into oral and injectable . Brivaracetam demonstrates under standard storage conditions, with no special temperature or humidity requirements specified for the bulk substance. Its (LogP) is 1.04, reflecting moderate that supports its handling in pharmaceutical preparations.

History and Development

Discovery and Preclinical Research

Brivaracetam was developed by UCB Pharma in the early as a high-affinity for protein 2A (), building on the novel mechanism of , which was patented in 1997 following its identification in 1992 through screening in audiogenic seizure-susceptible mice. The discovery program at UCB involved systematic optimization of levetiracetam analogs, screening approximately 12,000 compounds to enhance SV2A binding potency and selectivity while aiming for broader efficacy; brivaracetam, a 4-n-propyl , emerged as a lead candidate due to its superior profile. This rational approach addressed levetiracetam's moderate affinity and limitations in certain models, prioritizing compounds with rapid penetration and minimal off-target effects. Preclinical research in 2002 and subsequent years confirmed brivaracetam's enhanced binding affinity to in brain slices, with a Ki value of 0.05 μM—15- to 30-fold higher than levetiracetam's 1.6 μM—while maintaining selectivity over related proteins like SV2B. In audiogenic models using genetically susceptible mice, brivaracetam demonstrated potent activity, achieving complete suppression with an ED50 of 2.4 mg/kg (intraperitoneal), markedly lower than levetiracetam's 30 mg/kg, and extending efficacy to other models such as corneally kindled mice and hippocampal kindled s. These findings highlighted brivaracetam's faster onset and higher potency, correlating directly with occupancy levels in the brain. Toxicology evaluations in and dogs showed no evidence of across bacterial mutagenicity, chromosomal aberration, and assays. Long-term carcinogenicity studies in mice and rats revealed no tumorigenic effects at exposures providing margins exceeding 10 times the anticipated dose of 200 mg/day, with no-observed-adverse-effect levels (NOAELs) at 450 mg/kg/day in rats (approximately 150-fold dose margin). Acute and repeated-dose studies in these confirmed low , with therapeutic indices around 23 based on motor impairment thresholds. A key milestone occurred in 2003, when brivaracetam advanced to Phase II clinical trials following robust data from rodent models, marking the transition from early clinical validation to further .

Clinical Trials and Regulatory Approvals

The development of brivaracetam advanced to studies following promising preclinical in animal models of . The pivotal phase III randomized, double-blind, -controlled trials N01252 and N01253, conducted in 2014, evaluated adjunctive brivaracetam at doses of 50 to 200 mg/day in adults with uncontrolled partial-onset seizures despite one to two concomitant antiepileptic drugs. These trials demonstrated a 50% responder rate (defined as ≥50% reduction in partial-onset seizure frequency) significantly higher than (39-43% versus 22%), establishing with a favorable profile. Pediatric evaluation built on these findings through an open-label extension trial (NCT01364597, also referenced as N01396 in some reports), initiated in with long-term data analyzed up to 2023, which assessed adjunctive use in children and adolescents aged 1 month and older with partial-onset s. The study confirmed safety and tolerability, with no new safety signals emerging beyond those observed in adults, and maintained frequency reductions in most participants over up to four years of treatment. Regulatory approvals followed swiftly after the pivotal trials. The (EMA) granted marketing authorization for brivaracetam (as Briviact) on January 14, 2016, for adjunctive therapy of partial-onset seizures in adults and adolescents aged 16 years and older. In the United States, the (FDA) approved brivaracetam on February 18, 2016, initially for adjunctive treatment of partial-onset seizures in adults. The FDA expanded the indication on August 30, 2021, to include pediatric patients aged 1 month and older as adjunctive therapy, based on pharmacokinetic, safety, and efficacy data from pediatric trials showing comparable exposure and response to adults. In 2025, the FDA updated the prescribing information to include warnings for serious dermatologic reactions, such as Stevens-Johnson syndrome and , advising immediate discontinuation if signs appear and consideration of alternative therapies. Post-approval surveillance has reinforced brivaracetam's profile through long-term open-label studies, such as N01187, which reported retention rates exceeding 50% at 12 months in adults with focal seizures on adjunctive up to 200 mg/day, indicating sustained tolerability and efficacy. Recent 2025 analyses of real-world data highlight pharmacokinetic interactions with , where co-administration increased brivaracetam plasma levels by 107% to 280%, necessitating dose adjustments to avoid potential adverse effects like . Brivaracetam is now approved in over 50 countries worldwide, including the , , , , , and several in and , as adjunctive therapy for focal seizures. Ongoing clinical trials, such as NCT04666610 (initiated in 2020 and recruiting as of November 2025), are investigating brivaracetam as monotherapy in patients aged 2 to 25 years with childhood or juvenile absence epilepsy to potentially expand indications.

Society and Culture

Brand Names and Availability

Brivaracetam is primarily marketed under the brand name Briviact by UCB Pharma. Generic versions of brivaracetam have been available in the since 2022, with additional approvals for products such as Brivaracetam Zydus by Zydus Pharmaceuticals () Ltd in 2025. In the United States, no generic version is currently available, as patent protection for Briviact extends until April 9, 2030. Briviact is formulated as film-coated tablets in strengths of 10 mg, 25 mg, 50 mg, 75 mg, and 100 mg; an oral solution containing 10 mg/mL; and an intravenous solution at 10 mg/mL for injection or infusion. The medication is widely accessible in the United States, Europe, and several countries in Asia, as well as other regions including parts of North and South America and the Middle East, following regulatory approvals in these markets. Shortages have been reported occasionally in specific areas, such as Canada and parts of Europe, but they are generally resolved within weeks. In the US, a one-month supply without insurance costs approximately $1,700 as of 2025. UCB provides patient assistance programs, including the BRIVIACT Patient Assistance Program, to support uninsured or underinsured individuals in obtaining the medication at no cost or reduced rates, subject to eligibility criteria such as income level and residency in the . Brivaracetam is classified as a Schedule V in the United States under the due to its low potential for abuse relative to other controlled substances, stemming from its structural similarity to other racetams with known abuse potential. This scheduling imposes specific handling, storage, and dispensing requirements for prescribers and pharmacies to mitigate risks of misuse. Globally, brivaracetam is available only by prescription, reflecting its status as an antiepileptic drug requiring medical supervision for safe use in treating partial-onset seizures. The original U.S. patent for brivaracetam (US6911461) is set to expire on February 21, 2026. However, additional s, including US10729653, extend protection until April 9, 2030, delaying generic entry and increased competition until that time. Additionally, brivaracetam has received designation from the FDA for the treatment of childhood absence , granted on December 3, 2019, which provides incentives such as market exclusivity and tax credits to encourage development for rare subsets affecting fewer than 200,000 individuals in the U.S. Earlier designations include symptomatic in 2005, further supporting its targeted application in specific epileptic conditions. Economically, the global market for pharmaceutical-grade brivaracetam was valued at approximately $859 million in 2024 and is projected to reach $1,091.9 million in , driven by expanding indications and demand in treatment. In the U.S., brand-name brivaracetam (Briviact) incurs higher costs, often exceeding $1,000 monthly without , compared to generic versions available in markets like and , where production efficiencies and regulatory environments enable prices as low as one-tenth of U.S. levels due to reliance on imported active pharmaceutical ingredients. Access to brivaracetam is influenced by varying coverage, with many U.S. plans including Medicare and providing reimbursement but often requiring or step therapy to confirm necessity after trialing other antiepileptics. In 2025, FDA updates to the prescribing information for brivaracetam, including enhanced warnings on reactions and psychiatric adverse events issued on August 28, have implications for manufacturer liability, potentially increasing post-marketing surveillance requirements and influencing coverage decisions by payers concerned with .

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