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→‎Special groups: added text to section about studies fetal exposure to levetiracetam and exposure to the drug via breastmilk
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{{shortShort description|Medication}}
{{Use dmy dates|date=NovemberFebruary 20192024}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 419931567
| drug_name =
| imageL = Levetiracetam.svg
| widthL = 125
| altL =
| imageR = Levetiracetam ball-and-stick model.png
| widthR = 120
| altR =
 
<!--Clinical data-->
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| Drugs.com = {{drugs.com|monograph|levetiracetam}}
| MedlinePlus = a699059
| licence_EU = yes
| DailyMedID = Levetiracetam
| licence_US = Levetiracetam
| pregnancy_AU = B3
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web |title=Levetiracetam Use During Pregnancy |url=https://www.drugs.com/pregnancy/levetiracetam.html |website=Drugs.com |access-date=5 March 2019 |archive-date=6 March 2019 |archive-url=https://web.archive.org/web/20190306044746/https://www.drugs.com/pregnancy/levetiracetam.html |url-status=live }}</ref>
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| legal_AU = S4
| legal_BR = C1
| legal_BR_comment = <ref>{{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023-08-03 |access-date=2023-08-16 August 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=4 April 2023-04-04}}</ref>
| legal_CA = Rx-only
| legal_UK = POM
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| metabolism = Enzymatic hydrolysis of acetamide group
| elimination_half-life = 6–8 hrs
| excretion = Urinary[[Kidney]]
 
<!--Identifiers-->
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<!-- Side effects and mechanism -->
Common side effects of levetiracetam include sleepiness, dizziness, feeling tired, and aggression.<ref name=AHFS2019>{{cite web |title=Levetiracetam Monograph for Professionals |url=https://www.drugs.com/monograph/levetiracetam.html |website=Drugs.com |publisher=AHFS |access-date=14 January 2019 |language=en |archive-date=24 March 2019 |archive-url=https://web.archive.org/web/20190324134138/https://www.drugs.com/monograph/levetiracetam.html |url-status=live }}</ref> Severe side effects may include [[psychosis]], [[suicide]], and [[allergic reaction]]s such as [[Stevens–Johnson syndrome]] or [[anaphylaxis]].<ref name=AHFS2019/> Levetiracetam is the S-[[enantiomer]] of [[etiracetam]].<ref>{{cite book | vauthors = Cavanna AE |title=Behavioural Neurology of Anti-Epileptic Drugs: A Practical Guide |date=2018 |publisher=Oxford University Press |isbn=9780198791577 |page=17 |url=https://books.google.com/books?id=QVZYDwAAQBAJ&pg=PA17 }}</ref> Its mechanism of action is not yet clear.<ref name=AHFS2019/>
 
Levetiracetam was approved for medical use in the United States in 1999<ref name=AHFS2019/> and is available as a [[generic medication]].<ref name=BNF76>{{cite book|title=British national formulary: BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=9780857113382|pages=319|edition=76}}</ref> In 20202021, it was the 92nd101st most commonly prescribed medication in the United States, with more than 76{{nbsp}}million prescriptions.<ref>{{cite web | title = The Top 300 of 20202021 | url = https://clincalc.com/DrugStats/Top300Drugs.aspx | website = ClinCalc | access-date =14 7January October 20222024 | archive-date =15 12January February 20212024 | archive-url = https://web.archive.org/web/2021021214253420240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status = live }}</ref><ref>{{cite web | title = Levetiracetam - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Levetiracetam | accessurl-date status= 7 October 2022live | archive-date = 28 February 2020 | archive-url = https://web.archive.org/web/2020022805503920240104225509/https://clincalc.com/DrugStats/Drugs/Levetiracetam | urlarchive-statusdate=4 January 2024 |access-date=14 liveJanuary 2024 |website=ClinCalc}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref>
 
==Medical uses==
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===Other===
Levetiracetam has not been found to be useful for treatment of [[neuropathic pain]],<ref>{{cite journal | vauthors = Crawford-Faucher A, Huijon RM | title = The Role of Levetiracetam in Treating Chronic Neuropathic Pain Symptoms | journal = American Family Physician | volume = 92 | issue = 1 | pages = 23–24 | date = July 2015 | pmid = 26132123 | url = http://www.aafp.org/link_out?pmid=26132123 | access-date = 1 September 2017 | archive-date = 29 August 2021 | archive-url = https://web.archive.org/web/20210829200854/https://www.aafp.org/afp/2015/0701/p23.html | url-status = live }}</ref> nor for treatment of [[essential tremor]]s.<ref>{{cite journal | vauthors = Zesiewicz TA, Elble RJ, Louis ED, Gronseth GS, Ondo WG, Dewey RB, Okun MS, Sullivan KL, Weiner WJ | display-authors = 6 | title = Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology | journal = Neurology | volume = 77 | issue = 19 | pages = 1752–1755 | date = November 2011 | pmid = 22013182 | pmc = 3208950 | doi = 10.1212/WNL.0b013e318236f0fd }}</ref> Levetiracetam has not been found to be useful for treating all developmental disorders within the [[autism spectrum]],;<ref>{{cite journal | vauthors = Volkmar F, Siegel M, Woodbury-Smith M, King B, McCracken J, State M | title = Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder | journal = Journal of the American Academy of Child and Adolescent Psychiatry | volume = 53 | issue = 2 | pages = 237–257 | date = February 2014 | pmid = 24472258 | doi = 10.1016/j.jaac.2013.10.013 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hirota T, Veenstra-Vanderweele J, Hollander E, Kishi T | title = Antiepileptic medications in autism spectrum disorder: a systematic review and meta-analysis | journal = Journal of Autism and Developmental Disorders | volume = 44 | issue = 4 | pages = 948–957 | date = April 2014 | pmid = 24077782 | doi = 10.1007/s10803-013-1952-2 | s2cid = 36509998 }}</ref> studies have only proven to be an effective treatment for partial, myoclonic, or tonic-clonic seizures associated with autism spectrum disorder.<ref>{{cite journal | vauthors = Frye RE, Rossignol D, Casanova MF, Brown GL, Martin V, Edelson S, Coben R, Lewine J, Slattery JC, Lau C, Hardy P, Fatemi SH, Folsom TD, Macfabe D, Adams JB | display-authors = 6 | title = A review of traditional and novel treatments for seizures in autism spectrum disorder: findings from a systematic review and expert panel | journal = Frontiers in Public Health | volume = 1 | pages = 31 | date = September 2013 | pmid = 24350200 | pmc = 3859980 | doi = 10.3389/fpubh.2013.00031 | doi-access = free }}</ref>
 
=== Special groups ===
Data from several [https://pubmed.ncbi.nlm.nih.gov/30664067/ pregnancy studies] showed that children exposed to levetiracetam during pregnancy had the lowest risk of developing major congenital malformations compared to those exposed to other anti-seizure medications. Risk of major congenital malformations for children exposed to levetiracetam were within the range for children who were not exposed to any anti-seizure medications (ASMs) during pregnancy. [https://www.sciencedirect.com/science/article/abs/pii/S0890623814000380?via%3Dihub] [https://onlinelibrary.wiley.com/doi/10.1002/bdr2.1526] [https://n.neurology.org/content/82/3/213]
 
[https://pubmed.ncbi.nlm.nih.gov/35157004/ The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD)] study showed that most blood concentrations in breastfed infants of mothers taking levetiracetam were quite low, especially in relationship to the mother’s level and what the fetal level would have been during pregnancy. Median levetiracetam levels in breastfed infants were 5.3% of maternal levels. [https://jamanetwork.com/journals/jamaneurology/fullarticle/2758017] [https://pubmed.ncbi.nlm.nih.gov/32424708/%5D The Norwegian Mother and Child Cohort Study (MoBa)] showed that infant exposure to levetiracetam via breastmilk was not associated with negative neurodevelopment (such as lower IQ and autism spectrum disorder) at 36 months. [https://www.fhi.no/en/ch/studies/moba/]
 
Levetiracetam is known to undergo changes in clearance during pregnancy, so it’s important for healthcare providers to frequently check and, when necessary, adjust the levetiracetam dose of pregnant people with epilepsy.
 
Studies in female pregnant rats have shown minor fetal skeletal abnormalities when given maximum recommended human doses of levetiracetam orally throughout pregnancy and lactation.{{medical citation needed|date=September 2020}}
 
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=== Excretion ===
In persons with normal kidney function, levetiracetam is eliminated from the body primarily by the kidneys with about 66 percent of the original drug passed unchanged into urine. The plasma half-life of levetiracetam in adults is about 6 to 8 hours ,<ref name="Keppra tablet FDA label" /> although the mean CSF half life of approx. 24 hours better reflects levels at site of action.<ref>{{cite journal | vauthors = Steinhoff BJ, Staack AM | title = Levetiracetam and brivaracetam: a review of evidence from clinical trials and clinical experience | journal = Therapeutic Advances in Neurological Disorders | volume = 12 | pages = 1756286419873518 | date = January 2019 | pmid = 31523280 | pmc = 6734620 | doi = 10.1177/1756286419873518 }}</ref>
 
=== Analogues ===
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Levetiracetam is available as regular and extended release oral formulations and as intravenous formulations.<ref>{{Cite web|url=http://www.sagentpharma.com/wp-content/uploads/2015/05/Levetiracetam-Injection_PI.pdf|title=Levetiracetam Injection Prescribing Information|access-date=4 November 2015|archive-date=1 November 2018|archive-url=https://web.archive.org/web/20181101112508/http://www.sagentpharma.com/wp-content/uploads/2015/05/Levetiracetam-Injection_PI.pdf|url-status=live}}</ref>
 
The immediate release tablet has been available as a [[Generic drug|generic]] in the United States since 2008, and in the UK since 2011.<ref>{{cite web |title=Patent Terms Extended Under 35 USC §156 |url=http://www.uspto.gov/patent/laws-and-regulations/patent-term-extension/patent-terms-extended-under-35-usc-156 |website=www.uspto.gov |access-date=5 November 2015-11-05 |author=Branch Website Management |archive-date=15 November 2015 |archive-url=https://web.archive.org/web/20151115194741/http://www.uspto.gov/patent/laws-and-regulations/patent-term-extension/patent-terms-extended-under-35-usc-156 |url-status=live }}</ref><ref name="Mbizvo">{{cite journal | vauthors = Mbizvo GK, Dixon P, Hutton JL, Marson AG | title = Levetiracetam add-on for drug-resistant focal epilepsy: an updated Cochrane Review | journal = The Cochrane Database of Systematic Reviews | issue = 9 | pages = CD001901 | date = September 2012 | volume = 2012 | pmid = 22972056 | pmc = 7061650 | doi = 10.1002/14651858.cd001901.pub2 | author3-link = Jane Hutton }}</ref> The patent for the extended release tablet will expire in 2028.<ref>{{Cite web |url=http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/091291s000ltr.pdf |title=FDA Access Data |date=12 September 2011 |access-date=4 November 2015 |website=ANDA 091291 |publisher=Department of Health and Human Services |vauthors=Webber K |archive-date=4 March 2016 |archive-url=https://web.archive.org/web/20160304063413/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2011/091291s000ltr.pdf |url-status=live }}</ref>
 
The branded version Keppra is manufactured by [[UCB (company)|UCB Pharmaceuticals IncS.A.]]<ref name="Keppra SmPC" /><ref name="Keppra tablet FDA label" /><ref name="Keppra XR FDA label" /><ref name="Keppra IV FDA label" />
 
In 2015, Aprecia's [[3D printing|3D-printed]] [[orally disintegrating tablet]] form of the drug manufactured using [[3D printed medication|pharmaceutical 3D printing techniques]] was approved by the [[FDA]], under the trade name Spritam.<ref>{{cite web |title=FDA approves the first 3D-printed drug product |url=http://www.kurzweilai.net/fda-approves-the-first-3d-printed-drug-product |website=KurzweilAI |access-date=2015-10-14 October 2015 |date=13 October 2015 |archive-date=16 October 2015 |archive-url=https://web.archive.org/web/20151016233809/http://www.kurzweilai.net/fda-approves-the-first-3d-printed-drug-product |url-status=live }}</ref> Some have said that the drug has been improved by 3D printing, as the formula used now has improved disintegration properties.<ref>{{Cite journal | vauthors = Mohammed AA, Algahtani MS, Ahmad MZ, Ahmad J, Kotta S |date=1 December 2021-12-01 |title=3D Printing in medicine: Technology overview and drug delivery applications |journal=Annals of 3D Printed Medicine |series=3D-Printed Medicine: From today's accomplishments to tomorrow's promises |language=en |volume=4 |pages=100037 |doi=10.1016/j.stlm.2021.100037 |s2cid=244421616 |issn=2666-9641|doi-access=free }}</ref>
 
=== Legal status ===
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Additionally, Levetiracetam has been experimentally shown to reduce [[Levodopa-induced dyskinesia]],<ref>{{cite journal | vauthors = Du H, Nie S, Chen G, Ma K, Xu Y, Zhang Z, Papa SM, Cao X | display-authors = 6 | title = Levetiracetam Ameliorates L-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats Inducing Critical Molecular Changes in the Striatum | journal = Parkinson's Disease | volume = 2015 | issue = 1 | pages = 253878 | date = 27 January 2015 | pmid = 25692070 | pmc = 4322303 | doi = 10.1155/2015/253878 | publisher = [[Hindawi Publishing Corporation]] | publication-place = London, England, United Kingdom | veditors = Reichmann H, Alves da Costa C | lccn = 2010247839 | doi-access = free }}</ref> a type of movement disorder, or [[dyskinesia]] associated with the use of [[Levodopa]], a medication used to treat [[Parkinson's disease]].
 
Of the 10ten medications evaluated in a 2023 systematic review of the literature, levetiracetam was found to be the only medication with sufficient evidence showing that it may cause seizure freedom in some infants.<ref name=":0">{{Cite report | vauthors = Treadwell JR, Wu M, Tsou AY | location = Rockville (MD) | publisher = Agency for Healthcare Research and Quality (AHRQ) (US) | date = October 2022 | id = 22(23)-EHC004 Report No.: 2021-SR-01 | pmid = 36383706 | url = https://effectivehealthcare.ahrq.gov/products/management-infantile-epilepsy/research | title = Management of Infantile Epilepsies | doi = 10.23970/ahrqepccer252 | access-date = 12 July 2023 | archive-date = 5 July 2023 | archive-url = https://web.archive.org/web/20230705073433/https://effectivehealthcare.ahrq.gov/products/management-infantile-epilepsy/research | url-status = live }}</ref> Further, adverse effects from levetiracetam were rarely severe enough for the medication to be discontinued in this age group. Because available research included only 2 published studies reporting seizure freedom rates, however, the strength of the evidence was judged to be low.<ref name=":0" />
 
== References ==