Eslicarbazepine acetate

Last updated
Eslicarbazepine acetate
Eslicarbazepine acetate structure.svg
Clinical data
Trade names Aptiom, Zebinix, Exalief
AHFS/Drugs.com Monograph
License data
Pregnancy
category
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding ~30% [5]
Metabolism UGT (?)
Metabolites Eslicarbazepine (active), glucuronides (inactive), etc.
Elimination half-life 10–20 hours
Excretion ~90% renal
Identifiers
  • (S)-10-Acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.164.398 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H16N2O3
Molar mass 296.326 g·mol−1
3D model (JSmol)
  • CC(=O)O[C@H]1Cc2ccccc2N(C(N)=O)c2ccccc21
  • InChI=1S/C17H16N2O3/c1-11(20)22-16-10-12-6-2-4-8-14(12)19(17(18)21)15-9-5-3-7-13(15)16/h2-9,16H,10H2,1H3,(H2,18,21)/t16-/m0/s1
  • Key:QIALRBLEEWJACW-INIZCTEOSA-N

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. [6] [4] [3]

Contents

Similarly to oxcarbazepine, ESL behaves as a prodrug to (S)-(+)-licarbazepine. [7] As such, their mechanisms of action are identical. [8]

Contraindications

Eslicarbazepine acetate is contraindicated in people with second- or third-degree atrioventricular block, a type of heart block, and in people who are hypersensitive to eslicarbazepine, oxcarbazepine or carbamazepine. [9]

Adverse effects

Adverse effects are similar to oxcarbazepine. The most common ones (more than 10% of patients) are tiredness and dizziness. Other fairly common side effects (1 to 10%) include impaired coordination, gastrointestinal disorders such as diarrhoea, nausea and vomiting, rash (1.1%), and hyponatremia (low sodium blood levels, 1.2%). [3] [9] There may also be an increased risk of suicidal thoughts. [10]

Overdose

Symptoms of overdosing are similar to adverse effects of standard doses: severe hyponatraemia, somnolence, uncoordinated/unsteady gait, hemiparesis (weakness of one side of the body), along with visual and gastrointestinal disturbances. No specific antidote is available. Eslicarbazepine and metabolites can be dialyzed. [3] [9]

Interactions

Like oxcarbazepine, eslicarbazepine can reduce plasma levels of drugs that are metabolized by the liver enzymes CYP3A4 (verified in studies for simvastatin and the oral contraceptive levonorgestrel/ethinylestradiol) and UDP-glucuronosyltransferase, and increase plasma levels of drugs metabolized by CYP2C19. [3] [9]

Interaction studies have been conducted with a number of common anticonvulsants. Carbamazepine reduces blood plasma concentrations of eslicarbazepine, probably because it induces glucuronidation. This drug combination also increased the risk for diplopia, impaired coordination and dizziness in a clinical study. Phenytoin also reduces eslicarbazepine plasma concentrations, which may be due to increased glucuronidation of eslicarbazepine; and concomitant administration results in an increase in phenytoin serum concentrations, which is probably due to inhibition of CYP2C19. [10] Combinations with lamotrigine, topiramate, valproic acid or levetiracetam showed no significant interactions in studies, although eslicarbazepine has been shown to cause a minor reduction in lamotrigine levels. [9] [10]

Pharmacology

Mechanism of action

The active component, eslicarbazepine, has the same mechanism of action as oxcarbazepine (which is a prodrug for licarbazepine, the racemate of eslicarbazepine) and most likely the closely related carbamazepine. It stabilises the inactive state of voltage-gated sodium channels, allowing for less sodium to enter neural cells, which leaves them less excitable. [11] According to some sources, it has not been shown conclusively that this is the actual mechanism. [3] [9]

Pharmacokinetics

Eslicarbazepine acetate is absorbed to at least 90% from the gut, independently of food intake. It is quickly metabolised to eslicarbazepine, so that the original substance cannot be detected in the bloodstream. Peak plasma levels of eslicarbazepine are reached after 2–3 (1–4) hours, and plasma protein binding is somewhat less than 40%. Biological half-life is 10 to 20 hours, and steady-state concentrations are reached after four to five days after start of the treatment. [3] [9] Oxcarbazepine, for comparison, is also nearly completely absorbed from the gut, and peak plasma concentrations of licarbazepine are reached after 4.5 hours on average after oxcarbazepine intake. Plasma protein binding and half-life are of course the same. [12]

Other metabolites of ESL are the less active (R)-(−)-licarbazepine (5%; the stereoisomer of eslicarbazepine), the pharmacologically active oxcarbazepine (1%), and inactive glucuronides of all of these substances. The drug is excreted mainly via the urine, of which two thirds are in the form of eslicarbazepine and one third in the form of eslicarbazepine glucuronide. The other metabolites only account for a few percent of the excreted drug. [3] [9]

Pharmacogenomics

Persons with certain genetic variations in human leukocyte antigens (HLAs) are under increased risk of developing skin reactions such as acute generalized exanthematous pustulosis (AGEP), but also severe ones such as Stevens–Johnson and DRESS syndrome, under treatment with carbamazepine and drugs with related chemical structures. This is true for the HLA-A*3101 allele, which occurs in 2 to 5% of Europeans and 10% of Japanese people, and the HLA-B*1502 allele, which is mainly found in people of Asian descent. Theoretically, this may also apply to ESL. [9]

Chemistry

As the name suggests, eslicarbazepine acetate is the acetate ester prodrug of eslicarbazepine. Eslicarbazepine itself is the pharmacologically more active of the two stereoisomers of licarbazepine. [3] More specifically, it is (S)-(+)-licarbazepine.

Related drugs and active metabolites for comparison

History

Eslicarbazepine acetate was developed by the Portuguese pharmaceutical company Bial. In early 2009, Bial sold the marketing rights in Europe to the Japanese company Eisai. [13] The drug was approved in the European Union in April 2009 under the trade names Zebinix and Exalief, but was marketed only under the first name. [14] [15] In the US it is marketed by Sunovion (formerly Sepracor) and was approved in November 2013. [6]

Research

Studies for the use of ESL as an anticonvulsant for children are under way as of 2016. [16]

Like oxcarbazepine, ESL has potential uses for the treatment of trigeminal neuralgia [ citation needed ] and bipolar disorder. A 2015 assessment showed no statistical difference to placebo for the latter disorder. [17]

Related Research Articles

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

Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as a second-line agent in bipolar disorder. Carbamazepine appears to work as well as phenytoin and valproate for focal and generalized seizures. It is not effective for absence or myoclonic seizures.

<span class="mw-page-title-main">Valproate</span> Medication used for epilepsy, bipolar disorder and migraine

Valproate are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures. They can be given intravenously or by mouth, and the tablet forms exist in both long- and short-acting formulations.

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.

<span class="mw-page-title-main">Topiramate</span> Medication used to treat epilepsy and migraine

Topiramate, sold under the brand name Topamax among others, is a medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence and essential tremor. For epilepsy this includes treatment for generalized or focal seizures. It is taken orally.

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

Oxcarbazepine, sold under the brand name Trileptal among others, is a medication used to treat epilepsy. For epilepsy it is used for both focal seizures and generalized seizures. It has been used both alone and as add-on therapy in people with bipolar disorder who have had no success with other treatments. It is taken by mouth.

<span class="mw-page-title-main">Clopidogrel</span> Antiplatelet medication

Clopidogrel, sold under the brand name Plavix among others, is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following the placement of a coronary artery stent. It is taken by mouth. Its effect starts about two hours after intake and lasts for five days.

<span class="mw-page-title-main">Primidone</span> Barbiturate medication used to treat seizures and tremors

Primidone, sold under various brand names, is a barbiturate medication that is used to treat partial and generalized seizures and essential tremors. It is taken by mouth.

Bial is a pharmaceutical company headquartered in São Mamede do Coronado, in Trofa, Porto district, Portugal. It was founded in 1924, being among the largest companies of its kind in Portugal. Its products are sold in pharmacies in more than 58 countries in 4 continents: Europe, America, Africa and Asia.

<span class="mw-page-title-main">Clorazepate</span> Benzodiazepine medication

Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiazepine and serves as a prodrug for the equally long-lasting desmethyldiazepam, which is rapidly produced as an active metabolite. Desmethyldiazepam is responsible for most of the therapeutic effects of clorazepate.

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

Felbamate is an anticonvulsant used in the treatment of epilepsy. It is used to treat partial seizures in adults and partial and generalized seizures associated with Lennox–Gastaut syndrome in children. However, an increased risk of potentially fatal aplastic anemia and/or liver failure limit the drug's usage to severe refractory epilepsy.

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

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

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

Seletracetam is a pyrrolidone-derived drug of the racetam family that is structurally related to levetiracetam. It was under development by UCB Pharmaceuticals as a more potent and effective anticonvulsant drug to replace levetiracetam but its development has been halted.

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

Brivaracetam, sold under the brand name Briviact among others, is a chemical analog of levetiracetam, a racetam derivative with anticonvulsant (antiepileptic) properties. It is marketed by the pharmaceutical company UCB.

<span class="mw-page-title-main">Lacosamide</span> Anticonvulsant and analgesic medication

Lacosamide, sold under the brand name Vimpat among others, is a medication used for the treatment of partial-onset seizures and primary generalized tonic-clonic seizures. It is used by mouth or intravenously.

Drug rash with eosinophilia and systemic symptoms or drug reaction with eosinophilia and systemic symptoms (DRESS), also termed drug-induced hypersensitivity syndrome (DIHS), is a rare reaction to certain medications. It involves primarily a widespread skin rash, fever, swollen lymph nodes, and characteristic blood abnormalities such as an abnormally high level of eosinophils, low number of platelets, and increased number of atypical white blood cells (lymphocytes). However, DRESS is often complicated by potentially life-threatening inflammation of internal organs and the syndrome has about a 10% mortality rate. Treatment consists of stopping the offending medication and providing supportive care. Systemic corticosteroids are commonly used as well but no controlled clinical trials have assessed the efficacy of this treatment.

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

Elvitegravir (EVG) is an integrase inhibitor used to treat HIV infection. It was developed by the pharmaceutical company Gilead Sciences, which licensed EVG from Japan Tobacco in March 2008. The drug gained approval by the U.S. Food and Drug Administration on August 27, 2012, for use in adult patients starting HIV treatment for the first time as part of the fixed dose combination known as Stribild. On September 24, 2014, the FDA approved Elvitegravir as a single pill formulation under the trade name Vitekta. On November 5, 2015, the FDA approved the drug for use in patients affected with HIV-1 as a part of a second fixed dose combination pill known as Genvoya.

<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">Licarbazepine</span> Active metabolite of oxcarbazepine

Licarbazepine is a voltage-gated sodium channel blocker with anticonvulsant and mood-stabilizing effects that is related to oxcarbazepine. It is an active metabolite of oxcarbazepine. In addition, an enantiomer of licarbazepine, eslicarbazepine ((S)-(+)-licarbazepine), is an active metabolite of eslicarbazepine acetate. Oxcarbazepine and eslicarbazepine acetate are inactive on their own, and behave instead as prodrugs to licarbazepine and eslicarbazepine, respectively, to produce their therapeutic effects.

<span class="mw-page-title-main">Cabotegravir</span> Medication for HIV/AIDS

Cabotegravir, sold under the brand name Vocabria among others, is a antiretroviral medication used for the treatment of HIV/AIDS. It is available in the form of tablets and as an intramuscular injection, as well as in an injectable combination with rilpivirine under the brand name Cabenuva.

Antimanic drugs are psychotropic drugs that are used to treat symptoms of mania. Though there are different causes of mania, the majority is caused by bipolar disorder, therefore antimanic drugs are mostly similar to drugs treating bipolar disorder. Since 1970s, antimanic drugs have been used specifically to control the abnormal elevation of mood or mood swings during manic episodes. One purpose of antimanic drugs is to alleviate or shorten the duration of an acute mania. Another objective is to prevent further cycles of mania and maintain the improvement achieved during the acute episode. The mechanism of antimanic drugs has not yet been fully known, it is proposed that they mostly affect chemical neurotransmitters in the brain. However, the usage of antimanic drugs should be consulted with a doctor or pharmacist due to their side effects and interactions with other drugs and food.

References

  1. 1 2 "Zebinix". Therapeutic Goods Administration (TGA). 9 June 2021. Retrieved 6 September 2021.
  2. ↑ "Summary Basis of Decision (SBD) for Aptiom". Health Canada . 23 October 2014. Retrieved 29 May 2022.
  3. 1 2 3 4 5 6 7 8 9 "Aptiom- eslicarbazepine acetate tablet Aptiom- eslicarbazepine acetate kit". DailyMed. Retrieved 21 January 2021.
  4. 1 2 "Zebinix EPAR". European Medicines Agency (EMA). Retrieved 21 January 2021.
  5. ↑ Dinnendahl V, Fricke U, eds. (2011). Arzneistoff-Profile (in German). Vol. 4 (25 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN   978-3-7741-9846-3.
  6. 1 2 "FDA approves Aptiom to treat seizures in adults". US FDA. 8 November 2013. Archived from the original on 11 January 2017. Retrieved 16 December 2019.
  7. ↑ Rogawski MA (June 2006). "Diverse mechanisms of antiepileptic drugs in the development pipeline". Epilepsy Research. 69 (3): 273–94. doi:10.1016/j.eplepsyres.2006.02.004. PMC   1562526 . PMID   16621450.
  8. ↑ Rogawski MA, Löscher W (July 2004). "The neurobiology of antiepileptic drugs". Nature Reviews. Neuroscience. 5 (7): 553–64. doi:10.1038/nrn1430. PMID   15208697. S2CID   2201038.
  9. 1 2 3 4 5 6 7 8 9 Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. 2015. Zebinix.
  10. 1 2 3 "Zebinix 800mg tablets". Electronic Medicines Compendium (eMC). Retrieved 12 April 2017.
  11. ↑ Almeida L, Soares-da-Silva P (January 2007). "Eslicarbazepine acetate (BIA 2-093)". Neurotherapeutics. 4 (1): 88–96. doi: 10.1016/j.nurt.2006.10.005 . PMC   7479690 . PMID   17199020.
  12. ↑ Jasek W, ed. (2007). Austria-Codex (in German) (62nd ed.). Vienna: Österreichischer Apothekerverlag. p. 8384. ISBN   978-3-85200-181-4.
  13. ↑ "Eisai and Bial Announce Partnership Agreement for the European Commercialisation of the Novel Once Daily Anti-Epileptic Zebinix". PR Newswire. 19 February 2009.
  14. ↑ "Summary of Product Characteristics for Zebinix" (PDF). European Medicines Agency. p. 14. Archived from the original (PDF) on 2018-09-20. Retrieved 2016-05-22.
  15. ↑ "Exalief (eslicarbazepine acetate): Expiry of the marketing authorisation in the European Union" (PDF). European Medicines Agency. 30 July 2012. Archived from the original (PDF) on 20 September 2018. Retrieved 22 May 2016.
  16. ↑ Clinical trial number NCT00988156 for "Eslicarbazepine Acetate (BIA 2 093) as Therapy for Refractory Partial Seizures in Children" at ClinicalTrials.gov
  17. ↑ Grunze H, Kotlik E, Costa R, Nunes T, Falcão A, Almeida L, Soares-da-Silva P (March 2015). "Assessment of the efficacy and safety of eslicarbazepine acetate in acute mania and prevention of recurrence: experience from multicentre, double-blind, randomised phase II clinical studies in patients with bipolar disorder I". Journal of Affective Disorders. 174: 70–82. doi:10.1016/j.jad.2014.11.013. PMID   25484179.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.