Rufinamide

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Rufinamide
Rufinamide.svg
Clinical data
Trade names Banzel, Inovelon
AHFS/Drugs.com Monograph
MedlinePlus a609001
License data
Pregnancy
category
  • AU:B3
Routes of
administration
By mouth
ATC code
Legal status
Legal status
  • BR: Class C1 (Other controlled substances) [1]
  • UK: POM (Prescription only)
  • US: ℞-only [2]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability 85% (under fed conditions); tmax = 4–6 hours
Protein binding 34%
Metabolism Carboxylesterase-mediated hydrolysis (CYP not involved)
Metabolites Inactive
Elimination half-life 6–10 hours
Excretion Urine (85%) [2]
Identifiers
  • 1-(2,6-Difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C10H8F2N4O
Molar mass 238.198 g·mol−1
3D model (JSmol)
  • O=C(c1nnn(c1)Cc2c(F)cccc2F)N
  • InChI=1S/C10H8F2N4O/c11-7-2-1-3-8(12)6(7)4-16-5-9(10(13)17)14-15-16/h1-3,5H,4H2,(H2,13,17) Yes check.svgY
  • Key:POGQSBRIGCQNEG-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Rufinamide is an anticonvulsant medication. It is used in combination with other medication and therapy to treat Lennox–Gastaut syndrome [3] and various other seizure disorders. Rufinamide, a triazole derivative, was developed in 2004 by Novartis Pharma, AG, and is manufactured by Eisai.

Rufinamide was approved by the US Food and Drug Administration (FDA) in November 2008, as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children four years and older and adults. Its official FDA-approved labeling does not mention use in the treatment of partial seizures inasmuch as clinical trials submitted to the FDA were marginal. However, several recent clinical trials suggest that the drug has efficacy for partial seizures [4] It is marketed under the brand name Banzel. [5] It is also marketed in the European Union under the brand name Inovelon. [6] It is available as a generic medication. [7]

The mechanism of action of rufinamide is not fully understood. There is some evidence that rufinamide can modulate the gating of voltage-gated sodium channels, [8] [9] a common target for antiepileptic drugs. [10] A recent study indicates subtle effects on the voltage-dependence of gating and the time course of inactivation in some sodium channel isoforms that could reduce neuronal excitability. [11] However, this action cannot explain the unique spectrum of activity of rufinamide.

Related Research Articles

Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.

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Vigabatrin, sold under the brand names Sabril and Vigpoder, is a medication used to treat epilepsy. It became available as a generic medication in 2019.

<span class="mw-page-title-main">Lennox–Gastaut syndrome</span> Rare form of childhood-onset epilepsy

Lennox–Gastaut syndrome (LGS) is a complex, rare, and severe childhood-onset epilepsy syndrome. It is characterized by multiple and concurrent seizure types including tonic seizure, cognitive dysfunction, and slow spike waves on electroencephalogram (EEG), which are very abnormal. Typically, it presents in children aged 3–5 years and most of the time persists into adulthood with slight changes in the electroclinical phenotype. It has been associated with perinatal injuries, congenital infections, brain malformations, brain tumors, genetic disorders such as tuberous sclerosis and numerous gene mutations. Sometimes LGS is observed after infantile epileptic spasm syndrome. The prognosis for LGS is marked by a 5% mortality in childhood and persistent seizures into adulthood.

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Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxioselective anxiolytic since 1970, and an anticonvulsant since 1984. The primary drug-development goal was to provide greater anxiolytic, anti-obsessive efficacy with fewer benzodiazepine-related side effects.

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<span class="mw-page-title-main">Generalized epilepsy</span> Epilepsy syndrome that is characterised by generalised seizures with no apparent cause

Generalized epilepsy is a form of epilepsy characterised by generalised seizures with no apparent cause. Generalized seizures, as opposed to focal seizures, are a type of seizure that impairs consciousness and distorts the electrical activity of the whole or a larger portion of the brain.

<span class="mw-page-title-main">Brivaracetam</span> Medication used to treat seizures

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<span class="mw-page-title-main">Ganaxolone</span> Chemical compound

Ganaxolone, sold under the brand name Ztalmy, is a medication used to treat seizures in people with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder. Ganaxolone is a neuroactive steroid gamma-aminobutyric acid (GABA) A receptor positive modulator.

<span class="mw-page-title-main">Retigabine</span> Anticonvulsant, which works as a potassium-channel opener

Retigabine (INN) or ezogabine (USAN) is an anticonvulsant used as an adjunctive treatment for partial epilepsies in treatment-experienced adult patients. The drug was developed by Valeant Pharmaceuticals and GlaxoSmithKline. It was approved by the European Medicines Agency under the trade name Trobalt on March 28, 2011, and by the United States Food and Drug Administration (FDA), under the trade name Potiga, on June 10, 2011. Production was discontinued in June 2017.

<span class="mw-page-title-main">Perampanel</span> Anti-epileptic medication

Perampanel, sold under the brand name Fycompa, is an anti-epileptic medication developed by Eisai Co. that is used in addition to other drugs to treat partial seizures and generalized tonic-clonic seizures for people older than twelve years. It was first approved in 2012, and as of 2016, its optimal role in the treatment of epilepsy relative to other drugs was not clear. It was the first antiepileptic drug in the class of selective non-competitive antagonist of AMPA receptors.

<span class="mw-page-title-main">Eslicarbazepine acetate</span> Anticonvulsant medication

Eslicarbazepine acetate (ESL), sold under the brand names Aptiom and Zebinix among others, is an anticonvulsant medication approved for use in Europe and the United States as monotherapy or as additional therapy for partial-onset seizures epilepsy.

<span class="mw-page-title-main">Cenobamate</span> Anticonvulsant drug

Cenobamate, sold under the brand names Xcopri (US) and Ontozry (EU), is a medication used for the treatment of partial-onset seizures, a kind of epilepsy, in adults. It is taken by mouth.

References

  1. Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  2. 1 2 "Banzel- rufinamide tablet, film coated Banzel- rufinamide suspension". DailyMed. 15 April 2020. Retrieved 21 October 2020.
  3. Hakimian S, Cheng-Hakimian A, Anderson GD, Miller JW (August 2007). "Rufinamide: a new anti-epileptic medication". Expert Opinion on Pharmacotherapy. 8 (12): 1931–1940. doi:10.1517/14656566.8.12.1931. PMID   17696794. S2CID   19522242.
  4. Brodie MJ, Rosenfeld WE, Vazquez B, Sachdeo R, Perdomo C, Mann A, Arroyo S (August 2009). "Rufinamide for the adjunctive treatment of partial seizures in adults and adolescents: a randomized placebo-controlled trial". Epilepsia. 50 (8): 1899–1909. doi: 10.1111/j.1528-1167.2009.02160.x . PMID   19490053. S2CID   38485532.
  5. FDA press release - FDA Approves New Drug to Treat Severe Form of Epilepsy
  6. "European Public Assessment Report for rufinamide (INOVELON)". Archived from the original on 14 March 2009. Retrieved 25 November 2008.
  7. "2022 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 3 March 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
  8. Rogawski MA (June 2006). "Diverse mechanisms of antiepileptic drugs in the development pipeline". Epilepsy Research. 69 (3): 273–294. doi:10.1016/j.eplepsyres.2006.02.004. PMC   1562526 . PMID   16621450.
  9. Striano P, McMurray R, Santamarina E, Falip M (February 2018). "Rufinamide for the treatment of Lennox-Gastaut syndrome: evidence from clinical trials and clinical practice". Epileptic Disorders. 20 (1): 13–29. doi: 10.1684/epd.2017.0950 . PMID   29313492.
  10. Rogawski MA, Löscher W (July 2004). "The neurobiology of antiepileptic drugs". Nature Reviews. Neuroscience. 5 (7): 553–564. doi:10.1038/nrn1430. PMID   15208697. S2CID   2201038.
  11. Gilchrist J, Dutton S, Diaz-Bustamante M, McPherson A, Olivares N, Kalia J, et al. (May 2014). "Nav1.1 modulation by a novel triazole compound attenuates epileptic seizures in rodents". ACS Chemical Biology. 9 (5): 1204–1212. doi:10.1021/cb500108p. PMC   4027953 . PMID   24635129.