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Revision as of 12:17, 26 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank').← Previous edit Latest revision as of 04:56, 3 January 2025 edit undoBD2412 (talk | contribs)Autopatrolled, IP block exemptions, Administrators2,453,387 editsm Renamed references using RefRenamer 
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{{Short_description|Anticonvulsant medication}}
{{Drugbox
{{Use mdy dates|date=June 2024}}
| Watchedfields = changed
{{cs1 config |name-list-style=vanc |display-authors=6}}
| verifiedrevid = 417338401
{{Infobox drug
| IUPAC_name = (''S'')-3-(aminomethyl)-5-methylhexanoic acid
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 457473985
| image = Pregabalin.svg | image = Pregabalin.svg
| width = 152px | width = 200
| alt =

| caption =
<!--Clinical data-->
| image2 = Pregabalin ball-and-stick model.png
| tradename = Lyrica
| width2 = 215
| alt2 = <!-- Clinical data -->
| pronounce = {{IPAc-en|p|r|i|ˈ|g|æ|b|əl|ᵻ|n}}
| tradename = Lyrica, others<ref name="www.drugs.com-2016">{{cite web |title=Pregabalin |website=Drugs.com |url=https://www.drugs.com/pregabalin.html |access-date=November 7, 2016 |url-status=live |archive-url=https://web.archive.org/web/20190828172817/https://www.drugs.com/international/pregabalin.html |archive-date=August 28, 2019}}</ref>
| Drugs.com = {{drugs.com|monograph|pregabalin}} | Drugs.com = {{drugs.com|monograph|pregabalin}}
| MedlinePlus = a605045 | MedlinePlus = a605045
| DailyMedID = 5166 | DailyMedID = Pregabalin
| pregnancy_AU = D
| pregnancy_category = B3 <small>(])</small>, C <small>(])</small>
| pregnancy_AU_comment = <ref name="Australian Government Pregnancy-2023">{{cite web |title=Avoid prescribing pregabalin in pregnancy if possible |publisher=Australian Department of Health and Aged Care |url=https://www.tga.gov.au/news/safety-updates/avoid-prescribing-pregabalin-pregnancy-if-possible |access-date=February 13, 2023 |url-status=live |archive-url=https://web.archive.org/web/20230213035842/https://www.tga.gov.au/news/safety-updates/avoid-prescribing-pregabalin-pregnancy-if-possible |archive-date=February 13, 2023}}</ref><ref name="Australian Government Safety-2023">{{cite web |title=Product Information safety updates - January 2023 |publisher=Australian Department of Health and Aged Care |url=https://www.tga.gov.au/news/safety-updates/product-information-safety-updates-january-2023 |access-date=February 13, 2023 |url-status=live |archive-url=https://web.archive.org/web/20230213035847/https://www.tga.gov.au/news/safety-updates/product-information-safety-updates-january-2023 |archive-date=February 13, 2023}}</ref>
| legal_status = S4 <small>(Au)</small>, POM <small>(])</small>, Schedule V <small>(U.S.)</small>
| pregnancy_category =
| routes_of_administration = Oral(main), IV, Insufflation
| dependency_liability = ]: High<ref name="Sch2014"/><br />]: Moderate<ref name="Sch2014"/>
| addiction_liability = Low<ref name="Sch2014"/> (but varying with dosage and route of administration)
| routes_of_administration = ]
| class = {{hlist|]|]|]}}
| ATC_prefix = N02
| ATC_suffix = BF02
| ATC_supplemental = {{ATCvet|N02|BF02}}

<!-- Legal status -->| legal_AU = S4
| legal_AU_comment = <ref name="Therapeutic Goods Administration (TGA)-2022">{{cite web |title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 |website=Therapeutic Goods Administration (TGA) |date=June 21, 2022 |url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 |access-date=March 30, 2024 |url-status=live |archive-url=https://web.archive.org/web/20230706023149/https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 |archive-date=July 6, 2023}}</ref>
| legal_BR = C1
| legal_BR_comment = <ref name="Anvisa-2023">{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=March 31, 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 |publisher=] |language=pt-BR |publication-date=April 4, 2023 |url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |access-date=August 16, 2023 |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=August 3, 2023}}</ref>
| legal_CA = Rx-only
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III, or Unscheduled -->
| legal_DE_comment =
| legal_NZ = Rx-only
| legal_NZ_comment = <ref name="Lyrica Consumer Medicine Information-2023">{{cite web |title=Lyrica Consumer Medicine Information |url=https://www.medsafe.govt.nz/consumers/cmi/l/lyrica.pdf |access-date=December 4, 2023 |url-status=live |archive-url=https://web.archive.org/web/20231204180154/https://www.medsafe.govt.nz/consumers/cmi/l/lyrica.pdf |archive-date=December 4, 2023}}</ref>
| legal_UK = POM
| legal_UK_comment = /&nbsp;Class C<ref name="(emc)-2023">{{cite web |title=Lyrica Summary of Product Characteristics (SmPC) |website=(emc) |date=February 27, 2023 |url=https://www.medicines.org.uk/emc/product/5539/smpc |access-date=December 21, 2023 |url-status=live |archive-url=https://web.archive.org/web/20231221220209/https://www.medicines.org.uk/emc/product/5539/smpc |archive-date=December 21, 2023}}</ref>
| legal_US = Schedule V
| legal_US_comment = <ref name="DailyMed-2020"/>
| legal_EU = Rx-only
| legal_EU_comment = <ref name="Lyrica EPAR">{{cite web |title=Lyrica EPAR |website=] (EMA) |date=July 6, 2004 |url=https://www.ema.europa.eu/en/medicines/human/EPAR/lyrica |access-date=December 21, 2023 |url-status=live |archive-url=https://web.archive.org/web/20231221220208/https://www.ema.europa.eu/en/medicines/human/EPAR/lyrica |archive-date=December 21, 2023}}</ref>
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = Rx-only


<!--Pharmacokinetic data--> <!-- Pharmacokinetic data -->| bioavailability = Oral: ≥90%<ref name="EMA2013"/>
| protein_bound = <1%<ref name="Bock2010"/>
| bioavailability = ≥90%
| protein_bound = Nil | metabolism =
| metabolites = ]<ref name="EMA2013"/>
| metabolism = Negligible
| onset = May occur within a week (pain)<ref name="AHFS2019"/>
| elimination_half-life = 5–6.5 hours
| elimination_half-life = 4.5–7 hours<ref name="Expert Committee on Drug Dependence Forty-first Meeting-2018">{{cite report |author=Expert Committee on Drug Dependence Forty-first Meeting |location=Geneva |date=November 2018 |title=Critical Review Report: Pregabalin |publisher=World Health Organization |url=https://www.who.int/medicines/access/controlled-substances/Pregabalin_FINAL.pdf?ua=1 |archive-url=https://web.archive.org/web/20201026155408/https://www.who.int/medicines/access/controlled-substances/Pregabalin_FINAL.pdf?ua=1 |archive-date=October 26, 2020}}</ref> (mean 6.3 hours)<ref name="Expert Committee on Drug Dependence Forty-first Meeting-2018"/><ref name="pmid29261857">{{cite book |vauthors=Cross AL, Viswanath O, Sherman AI |chapter=Pregabalin |via=NCBI Bookshelf |title=StatPearls |location=Treasure Island (FL) |publisher=StatPearls Publishing |date=July 19, 2022 |pmid=29261857 |url=https://www.ncbi.nlm.nih.gov/books/NBK470341/ |access-date=August 27, 2022 |url-status=live |archive-url=https://web.archive.org/web/20220803171541/http://www.ncbi.nlm.nih.gov/books/NBK470341/ |archive-date=August 3, 2022}}</ref>
| excretion = ]
| duration_of_action = 8–12 hours <ref name="b403">{{cite web | title=BNF Pregabalin | publisher=NICE | date=2018-11-16 | url=https://bnf.nice.org.uk/drugs/pregabalin/#indications-and-dose | access-date=2024-06-19}}</ref>
| excretion = ]


<!--Identifiers--> <!-- Identifiers -->| CAS_number_Ref = {{cascite|correct|CAS}}
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 148553-50-8 | CAS_number = 148553-50-8
| ATC_prefix = N03 | CAS_supplemental =
| ATC_suffix = AX16
| PubChem = 5486971 | PubChem = 5486971
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00230 | DrugBank = DB00230
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| KEGG_Ref = {{keggcite|correct|kegg}} | KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02716 | KEGG = D02716
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 64356
| ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1059 | ChEMBL = 1059
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = 3-Isobutyl-GABA; (''S'')-3-Isobutyl-γ-aminobutyric acid; Isobutylgaba; CI-1008; PD-144723


<!--Chemical data--> <!-- Chemical and physical data -->| IUPAC_name = (3''S'')-3-(aminomethyl)-5-methylhexanoic acid
| C=8 | H=17 | N=1 | O=2 | C = 8
| H = 17
| molecular_weight = 159.23 g.mol<sup>-1</sup>
| N = 1
| smiles = O=C(O)C(CC(C)C)CN
| O = 2
| InChI = 1/C8H17NO2/c1-6(2)3-7(5-9)4-8(10)11/h6-7H,3-5,9H2,1-2H3,(H,10,11)/t7-/m0/s1
| SMILES = CC(C)CC(CC(=O)O)CN
| InChIKey = AYXYPKUFHZROOJ-ZETCQYMHBI
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C8H17NO2/c1-6(2)3-7(5-9)4-8(10)11/h6-7H,3-5,9H2,1-2H3,(H,10,11)/t7-/m0/s1 | StdInChI = 1S/C8H17NO2/c1-6(2)3-7(5-9)4-8(10)11/h6-7H,3-5,9H2,1-2H3,(H,10,11)/t7-/m0/s1
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = AYXYPKUFHZROOJ-ZETCQYMHSA-N | StdInChIKey = AYXYPKUFHZROOJ-ZETCQYMHSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}} }}


<!-- Definition and medical uses -->
'''Pregabalin''' (]) ({{pron-en|prɨˈɡæbəlɨn}}) is an ] drug used for ] and as an adjunct therapy for ]s with or without secondary ] in adults.<ref name="Benkert, Hippius">Benkert, O., Hippius, H. et al.: Kompendium der Psychiatrischen Pharmakotherapie, 6. Auflage, Springer Medizin Verlag, Heidelberg, 2007. (german) ISBN 9783540344018</ref> It has also been found effective for ] and is (as of 2007) approved for this use in the European Union.<ref name="Benkert, Hippius"/> It was designed as a more potent successor to ]. Pregabalin is marketed by ] under the trade name '''Lyrica'''. Pfizer described in a SEC filing that the drug could be used to treat epilepsy, post-herpetic neuralgia and diabetic peripheral neuropathy, fibromyalgia, ''et al''. Sales reached record $3,063 million in 2010.<ref></ref>
'''Pregabalin''', sold under the brand name '''Lyrica''' among others, is an ], ], and ] amino acid medication used to treat ], ], ], ], ], and ] (GAD).<ref name="AHFS2019"/><ref name="pmid25149863">{{cite journal |vauthors=Frampton JE |title=Pregabalin: a review of its use in adults with generalized anxiety disorder |journal=CNS Drugs |volume=28 |issue=9 |pages=835–854 |date=September 2014 |doi=10.1007/s40263-014-0192-0 |pmid=25149863 |s2cid=5349255}}</ref><ref name="pmid28888061">{{cite journal |vauthors=Iftikhar IH, Alghothani L, Trotti LM |title=Gabapentin enacarbil, pregabalin and rotigotine are equally effective in restless legs syndrome: a comparative meta-analysis |journal=European Journal of Neurology |volume=24 |issue=12 |pages=1446–1456 |date=December 2017 |doi=10.1111/ene.13449 |pmid=28888061 |s2cid=22262972}}</ref> Pregabalin also has ] properties.<ref name="Wyllie_2012">{{cite book |vauthors=Wyllie E, Cascino GD, Gidal BE, Goodkin HP |title=Wyllie's Treatment of Epilepsy: Principles and Practice |date=February 17, 2012 |publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-5348-4 |page=423 |url=https://books.google.com/books?id=j9t6Qg0kkuUC&pg=RA1-PA423}}</ref><ref name="Kirsch2013">{{cite book |vauthors=Kirsch D |title=Sleep Medicine in Neurology |date=October 10, 2013 |publisher=John Wiley & Sons |isbn=978-1-118-76417-6 |page=241 |url=https://books.google.com/books?id=Gf9QAQAAQBAJ&pg=PT241}}</ref><ref name="SchatzbergNemeroff2009">{{cite book |vauthors=Frye M, Moore K |title=The American Psychiatric Publishing Textbook of Psychopharmacology |year=2009 |isbn=978-1-58562-309-9 |veditors=Schatzberg AF, Nemeroff CB |pages=767–77 |chapter=Gabapentin and Pregabalin |chapter-url=https://books.google.com/books?id=Xx7iNGdV25IC&pg=PA767 |doi=10.1176/appi.books.9781585623860.as38 |access-date=September 1, 2022 |url-status=live |archive-url=https://web.archive.org/web/20240227031427/https://books.google.com/books?id=Xx7iNGdV25IC&pg=PA767#v=onepage&q&f=false |archive-date=February 27, 2024}}</ref> Its use in epilepsy is as an add-on therapy for ]s.<ref name="AHFS2019"/> When used before surgery, it reduces pain but results in greater sedation and visual disturbances.<ref name="pmid25209095">{{cite journal |vauthors=Mishriky BM, Waldron NH, Habib AS |title=Impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis |journal=British Journal of Anaesthesia |volume=114 |issue=1 |pages=10–31 |date=January 2015 |title-link=doi |doi=10.1093/bja/aeu293 |doi-access=free |pmid=25209095}}</ref> It is taken ].<ref name="AHFS2019"/>


<!-- Side effects and mechanism -->
Recent studies have shown that pregabalin is effective at treating chronic pain in disorders such as ]<ref>{{cite journal |author=Crofford LJ |title=Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial |journal=Arthritis Rheum |volume=52 |issue=4 |pages=1264–1273 |year=2005 |pmid=15818684 |doi=10.1002/art.20983 |author-separator=, |author2=Rowbotham MC |author3=Mease PJ |display-authors=3 |last4=Russell |first4=I. Jon |last5=Dworkin |first5=Robert H. |last6=Corbin |first6=Ann E. |last7=Young |first7=James P. |last8=Lamoreaux |first8=Linda K. |last9=Martin |first9=Susan A.}} </ref> and ].<ref>{{cite journal |author=Siddall PJ, Cousins MJ, Otte A, Griesing T, Chambers R, Murphy TK |title=Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial |journal=] |volume=67 |issue=10 |pages=1792–1800 |year=2006 |pmid=17130411 |doi=10.1212/01.wnl.0000244422.45278.ff}}</ref> In June 2007, pregabalin became the first medication approved by the U.S. ] specifically for the treatment of ].<ref name="FDAFibro">{{cite press release | url = http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108936.htm | title = FDA Approves First Drug for Treating Fibromyalgia | publisher = U.S. ] | date = June 21, 2007 | accessdate = 2010-10-30}}</ref>
Common side effects can include ], ], ], ], trouble with memory, ], ], problems with vision, and ].<ref name="AHFS2019" /><ref name="BNF76" /> Serious side effects may include ], and ].<ref name="AHFS2019" /> As with all other drugs approved by the FDA for treating epilepsy, the pregabalin labeling warns of an increased ] risk when combined with other drugs.<ref>{{cite journal | vauthors = Britton JW, Shih JJ | title = Antiepileptic drugs and suicidality | journal = Drug, Healthcare and Patient Safety | volume = 2 | pages = 181–189 | date = 2010 | pmid = 21701630 | pmc = 3108698 | doi = 10.2147/DHPS.S13225 | doi-access = free }}</ref><ref name="AHFS2019">{{cite web |title=Pregabalin |publisher=The American Society of Health-System Pharmacists |url=https://www.drugs.com/monograph/pregabalin.html |access-date=February 3, 2019 |url-status=live |archive-url=https://web.archive.org/web/20191202155555/https://www.drugs.com/monograph/pregabalin.html |archive-date=December 2, 2019}}</ref> When pregabalin is taken at high doses over a long period of time, addiction may occur, but if taken at ] the risk is low.<ref name="Sch2014">{{cite journal | vauthors = Schifano F | title = Misuse and abuse of pregabalin and gabapentin: cause for concern? | journal = CNS Drugs | volume = 28 | issue = 6 | pages = 491–496 | date = June 2014 | pmid = 24760436 | doi = 10.1007/s40263-014-0164-4 | title-link = doi | doi-access = free }}</ref> Use during pregnancy or breastfeeding is of unclear safety.<ref name="Preg2019">{{cite web |title=Pregabalin Use During Pregnancy |website=Drugs.com |url=https://www.drugs.com/pregnancy/pregabalin.html |access-date=February 4, 2019 |url-status=live |archive-url=https://web.archive.org/web/20190321033634/https://www.drugs.com/pregnancy/pregabalin.html |archive-date=March 21, 2019}}</ref>


It is a ] medication (]) which are drugs that are ]s of ] (GABA), an ].<ref name="pmid27345098">{{cite journal |vauthors=Calandre EP, Rico-Villademoros F, Slim M |year=2016 |title=Alpha2delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use |journal=Expert Rev Neurother |volume=16 |issue=11 |pages=1263–1277 |doi=10.1080/14737175.2016.1202764 |pmid=27345098 |s2cid=33200190}}</ref><ref name="pmid17222465">{{cite journal |vauthors=Dooley DJ, Taylor CP, Donevan S, Feltner D |year=2007 |title=Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission |journal=Trends Pharmacol. Sci. |volume=28 |issue=2 |pages=75–82 |doi=10.1016/j.tips.2006.12.006 |pmid=17222465}}</ref><ref name="WyllieCascino2012">{{cite book |author1=] |url=https://books.google.com/books?id=j9t6Qg0kkuUC&pg=RA1-PA423 |title=Wyllie's Treatment of Epilepsy: Principles and Practice |author2=Gregory D. Cascino |author3=Barry E. Gidal |author4=Howard P. Goodkin |date=February 17, 2012 |publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-5348-4 |page=423}}</ref><ref name="BenzonRathmell2013">{{cite book |author1=Honorio Benzon |url=https://books.google.com/books?id=kfcDAQAAQBAJ&pg=PA1006 |title=Practical Management of Pain |author2=James P. Rathmell |author3=Christopher L. Wu |author4=Dennis C. Turk |author5=Charles E. Argoff |author6=Robert W Hurley |date=September 11, 2013 |publisher=Elsevier Health Sciences |isbn=978-0-323-17080-2 |page=1006}}</ref> Although pregabalin is inactive at ] and GABA ], it acts by binding specifically to the α<sub>2</sub>δ-1 protein that was first described as an auxiliary subunit of ] ]s (See Pharmcodynamics).<ref name="AHFS2019" /><ref name="Cal2016">{{cite journal |vauthors=Calandre EP, Rico-Villademoros F, Slim M |date=November 2016 |title=Alpha<sub>2</sub>delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use |journal=Expert Review of Neurotherapeutics |volume=16 |issue=11 |pages=1263–1277 |doi=10.1080/14737175.2016.1202764 |pmid=27345098 |s2cid=33200190}}</ref><ref name="Uch2010">{{cite journal |vauthors=Uchitel OD, Di Guilmi MN, Urbano FJ, Gonzalez-Inchauspe C |year=2010 |title=Acute modulation of calcium currents and synaptic transmission by gabapentinoids |journal=Channels |volume=4 |issue=6 |pages=490–496 |doi=10.4161/chan.4.6.12864 |pmid=21150315 |doi-access=free |hdl-access=free |title-link=doi |hdl=11336/20897}}</ref>
It is considered to have a low potential for abuse, and a limited dependence liability if misused, and is thus classified as a ] drug in the U.S.<ref name="ScheduleV">{{cite journal | pmid = 16050051 | author-separator =, | author-name-separator= | volume=70 | issue=144 | year=2005 | month=July | pages=43633–5 | author1 = Drug Enforcement Administration, Department of Justice | title = Schedules of controlled substances: placement of pregabalin into schedule V. Final rule | journal = Federal register}}</ref>


<!-- History, society, and culture -->
Lyrica is one of four drugs which a subsidiary of Pfizer in 2009 pleaded guilty to misbranding "with the intent to ] or mislead". Pfizer agreed to pay $2.3 billion (£1.4 billion) in settlement, and entered a corporate integrity agreement. Pfizer illegally promoted the drugs and caused false claims to be submitted to government healthcare programs for uses that were not approved by the U.S. ] (FDA).<ref></ref>
Pregabalin was approved for medical use in the United States in 2004.<ref name="AHFS2019"/> It was developed as a successor to the related ].<ref name="Kaye-2014">{{cite book |vauthors=Kaye AD, Vadivelu N, Urman RD |title=Substance Abuse: Inpatient and Outpatient Management for Every Clinician |date=2014 |publisher=Springer |isbn=9781493919512 |page=324 |url=https://books.google.com/books?id=ms2lBQAAQBAJ&pg=PA324 |access-date=August 24, 2020 |url-status=live |archive-url=https://web.archive.org/web/20220301084046/https://books.google.com/books?id=ms2lBQAAQBAJ&pg=PA324 |archive-date=March 1, 2022}}</ref> It is available as a ].<ref name="BNF76">{{cite book |title=British National Formulary: BNF 76 |date=2018 |publisher=Pharmaceutical Press |isbn=9780857113382 |edition=76 |pages=323}}</ref><ref name="Generic Lyrica Availability">{{cite web |title=Generic Lyrica Availability |website=Drugs.com |url=https://www.drugs.com/availability/generic-lyrica.html |access-date=February 4, 2019 |url-status=live |archive-url=https://web.archive.org/web/20190327101443/https://www.drugs.com/availability/generic-lyrica.html |archive-date=March 27, 2019}}</ref><ref name="FDA approves first generics of Lyrica-2019">{{cite press release |title=FDA approves first generics of Lyrica |date=September 11, 2019 |website=U.S. ] (FDA) |url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-generics-lyrica |access-date=October 27, 2019 |url-status=live |archive-url=https://web.archive.org/web/20200609201441/https://www.fda.gov/news-events/press-announcements/fda-approves-first-generics-lyrica |archive-date=June 9, 2020}}</ref><ref name="USFDA-approval">{{cite web |title=Pregabalin ER: FDA-Approved Drugs |website=U.S. ] (FDA) |url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213226 |access-date=June 19, 2021 |url-status=live |archive-url=https://web.archive.org/web/20210624200922/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=213226 |archive-date=June 24, 2021}}</ref><ref name="USFDA-2023">{{cite web |title=Competitive Generic Therapy Approvals |website=U.S. ] (FDA) |date=June 29, 2023 |url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals |access-date=June 29, 2023 |url-status=live |archive-url=https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals |archive-date=June 29, 2023}}</ref> In 2022, it was the 91st most commonly prescribed medication in the United States, with more than 7{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Pregabalin Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Pregabalin | access-date = 30 August 2024 }}</ref> In the US, pregabalin is a ] controlled substance under the ],<ref name="AHFS2019"/> which means that the drug has low abuse potential compared to substances in Schedules I-IV, however, there is still a potential for misuse.<ref name="Is Lyrica a Controlled Substance-16 April 2024">{{cite web |title=Is Lyrica a Controlled Substance? |url=https://recovered.org/prescription-drugs/pregabalin-lyrica/pregabalin-lyrica-controlled-substance |access-date=May 6, 2024 |url-status=live |archive-url=https://web.archive.org/web/20240506185539/https://recovered.org/prescription-drugs/pregabalin-lyrica/pregabalin-lyrica-controlled-substance |archive-date=May 6, 2024}}</ref> Despite the low abuse potential, there have been reports of ], improved happiness, excitement, calmness, and a "high" similar to ] with the use of pregabalin; there is a potential for developing ] on these substances, and ] symptoms may occur if the medication is abruptly discontinued.<ref>{{cite web |title=Is Lyrica a controlled substance / Narcotic? |url=https://www.drugs.com/medical-answers/lyrica-controlled-substance-narcotic-3571636/ |access-date=May 6, 2024 |url-status=live |archive-url=https://web.archive.org/web/20240204164725/https://www.drugs.com/medical-answers/lyrica-controlled-substance-narcotic-3571636/ |archive-date=February 4, 2024}}</ref><ref name="pmid30726003">{{cite book |date=2024 |title=Prescription of Controlled Substances: Benefits and Risks |vauthors=Preuss CV, Kalava A, King KC |pmid=30726003}}</ref> It is a Class C controlled substance in the UK.<ref name="GOV.UK-2018"/> Therefore, pregabalin requires a prescription.<ref name="Controlled Drug Classes-2013">{{cite web |title=Controlled Drug Classes |date=August 12, 2013 |url=https://www.release.org.uk/law/classes |access-date=May 6, 2024 |url-status=live |archive-url=https://web.archive.org/web/20240328102114/https://www.release.org.uk/law/classes |archive-date=March 28, 2024}}</ref><ref name="What are Class C Drugs-2022">{{cite web |title=What are Class C Drugs? |date=October 31, 2022 |url=https://cpdonline.co.uk/knowledge-base/mental-health/what-are-class-c-drugs/ |access-date=May 6, 2024 |url-status=live |archive-url=https://web.archive.org/web/20240506185542/https://cpdonline.co.uk/knowledge-base/mental-health/what-are-class-c-drugs/ |archive-date=May 6, 2024}}</ref> Furthermore, the prescription must clearly set forth the dose.<ref name="circular-0192018">{{cite web |title=Control of pregabalin and gabapentin under the Misuse of Drugs Act 1971 |url=https://www.gov.uk/government/publications/circular-0192018-control-of-pregabalin-and-gabapentin-under-the-misuse-of-drugs-act-1971/control-of-pregabalin-and-gabapentin-under-the-misuse-of-drugs-act-1971 |access-date=February 21, 2024 |url-status=live |archive-url=https://web.archive.org/web/20240221044657/https://www.gov.uk/government/publications/circular-0192018-control-of-pregabalin-and-gabapentin-under-the-misuse-of-drugs-act-1971/control-of-pregabalin-and-gabapentin-under-the-misuse-of-drugs-act-1971 |archive-date=February 21, 2024}}</ref> Pregabalin has potential for misuse. It can bring about an ] in users. It can also have serious side effects, particularly when used in combination with other drugs.<ref name="circular-0192018"/><ref>{{cite web |title=Pregabalin and gabapentin to be controlled as class C drugs |url=https://www.gov.uk/government/news/pregabalin-and-gabapentin-to-be-controlled-as-class-c-drugs |access-date=April 2, 2020 |url-status=live |archive-url=https://web.archive.org/web/20201112034051/https://www.gov.uk/government/news/pregabalin-and-gabapentin-to-be-controlled-as-class-c-drugs |archive-date=November 12, 2020}}</ref>


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Pregabalin is available in 25, 50, 75, 100, 150, 200, 225, and 300&nbsp;mg capsules, and recently a ] flavoured oral solution has been developed, containing 20&nbsp;mg/mL with an added sweetening agent (]) to mask the chemical's bitter taste.<ref name="rxlist">http://www.rxlist.com/lyrica-drug.htm</ref><ref>http://priorartdatabase.com/IPCOM/000187748</ref> The maximum daily recommended dose for pregabalin is 600 mg. Dosages must be monitored and increases should be based on patient's tolerance. <ref name="rxlist" />


==History== ==Medical uses==
]
Pregabalin was invented by medicinal chemist ] at ] in the ]. The drug was approved in the European Union in 2004. Pregabalin received U.S. ] (FDA) approval for use in treating epilepsy, ] neuropathic pain, and ] in December 2004, and appeared on the U.S. market in ] 2005.<ref>{{cite journal |author=Dworkin RH, Kirkpatrick P |title=Pregabalin |journal=Nature Reviews Drug Discovery |volume=4 |pages=455–456 |year=2005 |month=June |url=http://www.nature.com/nrd/journal/v4/n6/pdf/nrd1756.pdf |format=PDF on free subscription |doi=10.1038/nrd1756 |pmid=15959952 |issue=6}}</ref>


===Seizures===
In June 2007, the FDA approved Lyrica as a treatment for ]. It was the first drug to be approved for this indication and remained the only one until ] (Cymbalta) gained FDA approval for the treatment of fibromyalgia in June 2008.<ref>http://www.fda.gov/ForConsumers/ConsumerUpdates/ucm107802.htm</ref>
For drug-resistant focal epilepsy, pregabalin is useful as an add-on therapy to other treatments.<ref name="pmid35349176">{{cite journal |vauthors=Panebianco M, Bresnahan R, Marson AG |title=Pregabalin add-on for drug-resistant focal epilepsy |journal=The Cochrane Database of Systematic Reviews |volume=3 |issue=3 |pages=CD005612 |date=March 2022 |doi=10.1002/14651858.CD005612.pub5 |pmc=8962962 |pmid=35349176}}</ref> Its use alone is less effective than some other seizure medications.<ref name="pmid23076957">{{cite journal |vauthors=Zhou Q, Zheng J, Yu L, Jia X |title=Pregabalin monotherapy for epilepsy |journal=The Cochrane Database of Systematic Reviews |volume=10 |pages=CD009429 |date=October 2012 |doi=10.1002/14651858.CD009429.pub2 |pmid=23076957}}</ref> It is unclear how it compares to ] for this use.<ref name="pmid23076957"/>


===Neuropathic pain===
The ] for Lyrica currently expires in October 2013. This is the earliest possible date that a ] version of Lyrica could become available. However, there are other circumstances that could come up to extend the exclusivity period of Lyrica beyond 2013. These circumstances could include things such as lawsuits or other patents for specific Lyrica uses. Once Lyrica goes off patent, there may be several companies that manufacture a generic Lyrica drug.
The European Federation of Neurological Societies recommends pregabalin as a first-line agent for the treatment of pain associated with ], ], and ].<ref name="pmid20402746">{{cite journal |vauthors=Attal N, Cruccu G, Baron R, Haanpää M, Hansson P, Jensen TS, Nurmikko T |title=EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision |journal=European Journal of Neurology |volume=17 |issue=9 |pages=1113–1e88 |date=September 2010 |title-link=doi |doi=10.1111/j.1468-1331.2010.02999.x |doi-access=free |pmid=20402746 |s2cid=14236933}}</ref> A minority obtain substantial benefit, and a larger number obtain moderate benefit.<ref name="Derry_2019">{{cite journal |vauthors=Derry S, Bell RF, Straube S, Wiffen PJ, Aldington D, Moore RA |title=Pregabalin for neuropathic pain in adults |journal=The Cochrane Database of Systematic Reviews |volume=1 |pages=CD007076 |date=January 2019 |issue=1 |doi=10.1002/14651858.CD007076.pub3 |pmc=6353204 |pmid=30673120}}</ref> It is given equal weight as ] and ]s as a first-line agent, however, the latter are less expensive as of 2010.<ref name="pmid20705215">{{cite journal |vauthors=Finnerup NB, Sindrup SH, Jensen TS |title=The evidence for pharmacological treatment of neuropathic pain |journal=Pain |volume=150 |issue=3 |pages=573–581 |date=September 2010 |doi=10.1016/j.pain.2010.06.019 |pmid=20705215 |s2cid=29830155}}</ref> Pregabalin is as effective at relieving pain as ] and ]. ] of pregabalin and amitriptyline or duloxetine offers additional pain relief for people whose pain is not adequately controlled with one medication and is safe.<ref name="NIHR Evidence-2023">{{cite journal |date=April 6, 2023 |title=Combination therapy for painful diabetic neuropathy is safe and effective |journal=NIHR Evidence |language=en |doi=10.3310/nihrevidence_57470 |s2cid=258013544 |url=https://evidence.nihr.ac.uk/alert/combination-therapy-for-painful-diabetic-neuropathy-is-safe-and-effective/ |url-access=subscription |access-date=April 28, 2023 |url-status=live |archive-url=https://web.archive.org/web/20230428104720/https://evidence.nihr.ac.uk/alert/combination-therapy-for-painful-diabetic-neuropathy-is-safe-and-effective/ |archive-date=April 28, 2023}}</ref><ref name="pmid36007534">{{cite journal |vauthors=Tesfaye S, Sloan G, Petrie J, White D, Bradburn M, Julious S, Rajbhandari S, Sharma S, Rayman G, Gouni R, Alam U, Cooper C, Loban A, Sutherland K, Glover R, Waterhouse S, Turton E, Horspool M, Gandhi R, Maguire D, Jude EB, Ahmed SH, Vas P, Hariman C, McDougall C, Devers M, Tsatlidis V, Johnson M, Rice AS, Bouhassira D, Bennett DL, Selvarajah D |title=Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial |journal=Lancet |volume=400 |issue=10353 |pages=680–690 |date=August 2022 |doi=10.1016/s0140-6736(22)01472-6 |pmc=9418415 |pmid=36007534}}</ref>


Studies have shown that higher doses of pregabalin are associated with greater efficacy.<ref name="Freynhagen Baron Kawaguchi Malik pp. 1–9">{{cite journal |vauthors=Freynhagen R, Baron R, Kawaguchi Y, Malik RA, Martire DL, Parsons B, Rey RD, Schug SA, Jensen TS, Tölle TR, Ushida T, Whalen E |title=Pregabalin for neuropathic pain in primary care settings: recommendations for dosing and titration |journal=Postgraduate Medicine |volume=133 |issue=1 |pages=1–9 |date=January 2021 |publisher=Informa UK Limited |doi=10.1080/00325481.2020.1857992 |doi-access=free |pmid=33423590 |s2cid=231574963 |url=https://pure.au.dk/portal/files/274258964/00325481.2020.pdf |access-date=February 19, 2024 |url-status=live |archive-url=https://web.archive.org/web/20240227025752/https://pure.au.dk/ws/portalfiles/portal/274258964/00325481.2020.pdf |archive-date=February 27, 2024}}</ref>
==Indications==
]


Pregabalin's use in cancer-associated neuropathic pain is controversial,<ref name="Bennett 1681–8">{{cite journal |vauthors=Bennett MI, Laird B, van Litsenburg C, Nimour M |title=Pregabalin for the management of neuropathic pain in adults with cancer: a systematic review of the literature |journal=Pain Medicine |volume=14 |issue=11 |pages=1681–1688 |date=November 2013 |title-link=doi |doi=10.1111/pme.12212 |doi-access=free |pmid=23915361}}</ref> though such use is common.<ref name="Howard-2017">{{cite book |vauthors=Howard P |title=Palliative care formulary. |date=2017 |publisher=Pharmaceutical press |isbn=978-0-85711-348-1 |edition=6 |page=Chapter 4 Central Nervous System}}</ref> It has been examined for the prevention of post-surgical chronic pain, but its utility for this purpose is controversial.<ref name="pmid22415535">{{cite journal |vauthors=Clarke H, Bonin RP, Orser BA, Englesakis M, Wijeysundera DN, Katz J |title=The prevention of chronic postsurgical pain using gabapentin and pregabalin: a combined systematic review and meta-analysis |journal=Anesthesia and Analgesia |volume=115 |issue=2 |pages=428–442 |date=August 2012 |doi=10.1213/ANE.0b013e318249d36e |hdl=10315/27968 |hdl-access=free |pmid=22415535 |s2cid=18933131}}</ref><ref name="pmid23881791">{{cite journal |vauthors=Chaparro LE, Smith SA, Moore RA, Wiffen PJ, Gilron I |title=Pharmacotherapy for the prevention of chronic pain after surgery in adults |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue=7 |pages=CD008307 |date=July 2013 |doi=10.1002/14651858.CD008307.pub2 |pmc=6481826 |pmid=23881791}}</ref>
Pregabalin is indicated for:
* Treatment of ] from diabetic neuropathy or post herpetic neuralgia. There is not enough data to state that it should be used in all neuropathic pain.
* Adjunctive therapy in adults with partial seizures with or without secondary generalization
* ]
* ] (approved in the ]).<ref name="GAD">{{cite press release |url=http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/03-27-2006/0004327379 |title=Pfizer's Lyrica Approved for the Treatment of Generalized Anxiety Disorder (GAD) in Europe |accessdate=2007-07-04 |format= |work=}}</ref><ref name="Bandelow-2007">{{Cite journal | last1 = Bandelow | first1 = B. | last2 = Wedekind | first2 = D. | last3 = Leon | first3 = T. | title = Pregabalin for the treatment of generalized anxiety disorder: a novel pharmacologic intervention | journal = Expert Rev Neurother | volume = 7 | issue = 7 | pages = 769–781 | month = Jul | year = 2007 | doi = 10.1586/14737175.7.7.769 | pmid = 17610384 }}</ref>


Pregabalin is generally not regarded as efficacious in the treatment of acute pain.<ref name="Derry_2019"/> In trials examining the utility of pregabalin for the treatment of acute post-surgical pain, no effect on overall pain levels was observed, but people did require less morphine and had fewer opioid-related side effects.<ref name="pmid22415535"/><ref name="pmid27535436">{{cite journal |vauthors=Hamilton TW, Strickland LH, Pandit HG |title=A Meta-Analysis on the Use of Gabapentinoids for the Treatment of Acute Postoperative Pain Following Total Knee Arthroplasty |journal=The Journal of Bone and Joint Surgery. American Volume |volume=98 |issue=16 |pages=1340–1350 |date=August 2016 |doi=10.2106/jbjs.15.01202 |pmid=27535436 |url=https://ora.ox.ac.uk/objects/uuid:cbe29197-14a9-47dc-b961-2ad3e24fd1c0 |url-access=subscription |access-date=August 24, 2020 |url-status=live |archive-url=https://web.archive.org/web/20200929012600/https://ora.ox.ac.uk/objects/uuid:cbe29197-14a9-47dc-b961-2ad3e24fd1c0 |archive-date=September 29, 2020}}</ref> Several possible mechanisms for pain improvement have been discussed.<ref name="pmid27069626">{{cite journal |vauthors=Patel R, Dickenson AH |title=Mechanisms of the gabapentinoids and α 2 δ-1 calcium channel subunit in neuropathic pain |journal=Pharmacology Research & Perspectives |volume=4 |issue=2 |pages=e00205 |date=April 2016 |doi=10.1002/prp2.205 |pmc=4804325 |pmid=27069626}}</ref>
Usually physicians will start the patient on a low dose of pregabalin and increase it gradually, depending on the patient's evaluation. Its therapeutic effect appears after 1 week of use and is similar in effectiveness to ], ] and ] but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of ] and additionally unlike benzodiazepines it does not disrupt ] and produces less severe cognitive and psychomotor impairment; it also has a low potential for abuse and dependence and may be preferred over the ]s for these reasons.<ref name="Bandelow-2007"/><ref>{{Cite journal | last1 = Owen | first1 = RT. | title = Pregabalin: its efficacy, safety and tolerability profile in generalized anxiety | journal = Drugs Today (Barc) | volume = 43 | issue = 9 | pages = 601–10 | month = Sep | year = 2007 | doi = 10.1358/dot.2007.43.9.1133188 | pmid = 17940637 }}</ref>


===Anxiety disorders===
It has not been found to be effective for ]-associated ].<ref>{{cite journal |author=Simpson DM |title=Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial |journal=Neurology |volume=74 |issue=5 |pages=413–420 |year=2010 |month=February |pmid=20124207 |doi=10.1212/WNL.0b013e3181ccc6ef |url= |pmc=2816006 |author-separator=, |author2=Schifitto G |author3=Clifford DB |display-authors=3 |last4=Murphy |first4=T. K. |last5=Durso-De Cruz |first5=E. |last6=Glue |first6=P. |last7=Whalen |first7=E. |last8=Emir |first8=B. |last9=Scott |first9=G. N.}}</ref>
Pregabalin is effective for treatment of ].<ref name="pmid30712879">{{cite journal |vauthors=Slee A, Nazareth I, Bondaronek P, Liu Y, Cheng Z, Freemantle N |title=Pharmacological treatments for generalised anxiety disorder: a systematic review and network meta-analysis |journal=Lancet |volume=393 |issue=10173 |pages=768–777 |date=February 2019 |doi=10.1016/S0140-6736(18)31793-8 |pmid=30712879 |s2cid=72332967 |url=https://discovery.ucl.ac.uk/id/eprint/10070219/1/Freemantle_Slee_GAD_Meta_Text%20R1_20180627%20clean.pdf |access-date=September 8, 2020 |url-status=live |archive-url=https://web.archive.org/web/20200313031825/https://discovery.ucl.ac.uk/id/eprint/10070219/1/Freemantle_Slee_GAD_Meta_Text%20R1_20180627%20clean.pdf |archive-date=March 13, 2020}}; {{cite web |title=Supplemental Appendices |date=June 5, 2018 |url=https://discovery.ucl.ac.uk/id/eprint/10070219/7/Freemantle_Slee_GAD_Web_Appendix%20R1_20180627.pdf |archive-url=https://web.archive.org/web/20200309183455/https://discovery.ucl.ac.uk/id/eprint/10070219/7/Freemantle_Slee_GAD_Web_Appendix%20R1_20180627.pdf |archive-date=March 9, 2020}}; {{cite web |title=Authors' Reply |date=June 5, 2018 |url=https://discovery.ucl.ac.uk/id/eprint/10084194/3/Nazareth_Lancet%20Correspondence051019.pdf |archive-url=https://web.archive.org/web/20201017231136/https://discovery.ucl.ac.uk/id/eprint/10084194/3/Nazareth_Lancet%20Correspondence051019.pdf |archive-date=October 17, 2020}}</ref> It is also effective for the short- and long-term treatment of ] and in reducing ].<ref name="NIHR Evidence-2022">{{cite journal |date=October 17, 2022 |title=Review finds little evidence to support gabapentinoid use in bipolar disorder or insomnia |journal=NIHR Evidence |type=Plain English summary |language=en |publisher=National Institute for Health and Care Research |doi=10.3310/nihrevidence_54173 |s2cid=252983016 |url=https://evidence.nihr.ac.uk/alert/review-finds-little-evidence-support-gabapentinoid-use-bipolar-disorder-or-insomnia/ |url-access=subscription |access-date=October 27, 2022 |url-status=live |archive-url=https://web.archive.org/web/20221127080508/https://evidence.nihr.ac.uk/alert/review-finds-little-evidence-support-gabapentinoid-use-bipolar-disorder-or-insomnia/ |archive-date=November 27, 2022}}</ref><ref name="Hong_2022">{{cite journal |vauthors=Hong JS, Atkinson LZ, Al-Juffali N, Awad A, Geddes JR, Tunbridge EM, Harrison PJ, Cipriani A |title=Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale |journal=Molecular Psychiatry |volume=27 |issue=3 |pages=1339–1349 |date=March 2022 |doi=10.1038/s41380-021-01386-6 |pmc=9095464 |pmid=34819636}}</ref> However, there is concern regarding pregabalin's off-label use due to the lack of strong scientific evidence for its efficacy in multiple conditions and its proven side effects.<ref name="pmid34819636">{{cite journal |vauthors=Hong JS, Atkinson LZ, Al-Juffali N, Awad A, Geddes JR, Tunbridge EM, Harrison PJ, Cipriani A |date=March 2022 |title=Gabapentin and pregabalin in bipolar disorder, anxiety states, and insomnia: Systematic review, meta-analysis, and rationale |journal=Molecular Psychiatry |volume=27 |issue=3 |pages=1339–1349 |doi=10.1038/s41380-021-01386-6 |pmc=9095464 |pmid=34819636}}</ref>

The World Federation of Biological Psychiatry recommends pregabalin as one of several first line agents for the treatment of generalized anxiety disorder, but recommends other agents such as those of ] (SSRI) class as first line treatment for ] (OCD) and ] (PTSD).<ref name="pmid22540422">{{cite journal |vauthors=Bandelow B, Sher L, Bunevicius R, Hollander E, Kasper S, Zohar J, Möller HJ |date=June 2012 |title=Guidelines for the pharmacological treatment of anxiety disorders, obsessive-compulsive disorder and posttraumatic stress disorder in primary care |journal=International Journal of Psychiatry in Clinical Practice |volume=16 |issue=2 |pages=77–84 |doi=10.3109/13651501.2012.667114 |pmid=22540422 |s2cid=16253034 |url=https://www.wfsbp.org/fileadmin/user_upload/Treatment_Guidelines/Bandelow_et_al_01.pdf |access-date=October 16, 2020 |url-status=live |archive-url=https://web.archive.org/web/20180403134713/http://www.wfsbp.org/fileadmin/user_upload/Treatment_Guidelines/Bandelow_et_al_01.pdf |archive-date=April 3, 2018}}</ref><ref name="pmid22395254">{{cite journal |vauthors=Wensel TM, Powe KW, Cates ME |date=March 2012 |title=Pregabalin for the treatment of generalized anxiety disorder |journal=The Annals of Pharmacotherapy |volume=46 |issue=3 |pages=424–429 |doi=10.1345/aph.1Q405 |pmid=22395254 |s2cid=26320851}}</ref> For PTSD, pregabalin as complementary treatment seems to be effective.<ref name="Hong_2022"/>

====Generalized anxiety disorder====
Pregabalin has ] effects similar to ] with less risk of ].<ref name="pmid17940637"/> The effects of pregabalin appear within one week of use,<ref name="Drugs.com-2021">{{cite web |title=How long does it take for Lyrica to work? |website=Drugs.com |date=May 25, 2021 |url=https://www.drugs.com/medical-answers/long-lyrica-work-3558304/ |access-date=February 18, 2022 |url-status=live |archive-url=https://web.archive.org/web/20220218195925/https://www.drugs.com/medical-answers/long-lyrica-work-3558304/ |archive-date=February 18, 2022}}</ref> and are similar in effectiveness to ], ], and ], but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for ] anxiety symptoms.<ref name="pmid17610384"/> Long-term trials have shown continued effectiveness without the development of ], and, in addition, unlike benzodiazepines, it has a beneficial effect on sleep and ], characterized by the enhancement of ].<ref name="pmid17610384"/> It produces less severe cognitive and psychomotor impairment compared to benzodiazepines.<ref name="pmid17610384">{{cite journal |vauthors=Bandelow B, Wedekind D, Leon T |title=Pregabalin for the treatment of generalized anxiety disorder: a novel pharmacologic intervention |journal=Expert Review of Neurotherapeutics |volume=7 |issue=7 |pages=769–781 |date=July 2007 |doi=10.1586/14737175.7.7.769 |pmid=17610384 |s2cid=6229344}}</ref><ref name="pmid17940637">{{cite journal |vauthors=Owen RT |title=Pregabalin: its efficacy, safety and tolerability profile in generalized anxiety |journal=Drugs of Today |volume=43 |issue=9 |pages=601–610 |date=September 2007 |doi=10.1358/dot.2007.43.9.1133188 |pmid=17940637}}</ref>

A 2019 review found that pregabalin reduces symptoms, and was generally well tolerated.<ref name="pmid30712879"/>

===Other uses===
Although pregabalin is sometimes prescribed for people with ], there is no evidence showing that it is effective.<ref name="Hong_2022"/><ref name="pmid34577534">{{cite journal |vauthors=Ng QX, Han MX, Teoh SE, Yaow CY, Lim YL, Chee KT |title=A Systematic Review of the Clinical Use of Gabapentin and Pregabalin in Bipolar Disorder |journal=Pharmaceuticals |volume=14 |issue=9 |pages=834 |date=August 2021 |doi=10.3390/ph14090834 |doi-access=free |pmc=8469561 |pmid=34577534}}</ref>

There is no evidence and significant risk in using pregabalin for ] and ].<ref name="pmid34637958">{{cite journal |vauthors=Giménez-Campos MS, Pimenta-Fermisson-Ramos P, Díaz-Cambronero JI, Carbonell-Sanchís R, López-Briz E, Ruíz-García V |title=A systematic review and meta-analysis of the effectiveness and adverse events of gabapentin and pregabalin for sciatica pain |journal=Atencion Primaria |volume=54 |issue=1 |pages=102144 |date=January 2022 |publisher=Elsevier BV |doi=10.1016/j.aprim.2021.102144 |pmc=8515246 |pmid=34637958}}</ref><ref name="pmid28809936">{{cite journal |vauthors=Shanthanna H, Gilron I, Rajarathinam M, AlAmri R, Kamath S, Thabane L, Devereaux PJ, Bhandari M |title=Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials |journal=PLOS Medicine |volume=14 |issue=8 |pages=e1002369 |date=August 2017 |doi=10.1371/journal.pmed.1002369 |doi-access=free |pmc=5557428 |pmid=28809936}}</ref><ref name="Mannix-2018">{{cite news |vauthors=Mannix L |date=December 18, 2018 |title=This popular drug is linked to addiction and suicide. Why do doctors keep prescribing it? |work=] |url=https://www.canberratimes.com.au/national/victoria/this-popular-drug-is-linked-to-addiction-and-suicide-why-do-doctors-keep-prescribing-it-20181129-p50j1x.html |access-date=December 18, 2018 |archive-url=https://web.archive.org/web/20181218193541/https://www.canberratimes.com.au/national/victoria/this-popular-drug-is-linked-to-addiction-and-suicide-why-do-doctors-keep-prescribing-it-20181129-p50j1x.html |archive-date=December 18, 2018}}</ref> Evidence of benefit in ] as well as withdrawal from certain other drugs is limited as of 2016.<ref name="pmid27848217">{{cite journal |vauthors=Freynhagen R, Backonja M, Schug S, Lyndon G, Parsons B, Watt S, Behar R |title=Pregabalin for the Treatment of Drug and Alcohol Withdrawal Symptoms: A Comprehensive Review |journal=CNS Drugs |volume=30 |issue=12 |pages=1191–1200 |date=December 2016 |doi=10.1007/s40263-016-0390-z |pmc=5124051 |pmid=27848217}}</ref>

There is no evidence for its use in the prevention of ]s and gabapentin has also been found not to be useful.<ref name="pmid23797675">{{cite journal |vauthors=Linde M, Mulleners WM, Chronicle EP, McCrory DC |title=Gabapentin or pregabalin for the prophylaxis of episodic migraine in adults |journal=The Cochrane Database of Systematic Reviews |volume=6 |issue=6 |pages=CD010609 |date=June 2013 |doi=10.1002/14651858.CD010609 |pmc=6599858 |pmid=23797675}}</ref>


==Adverse effects== ==Adverse effects==
Exposure to pregabalin is associated with weight gain, drowsiness, fatigue, dizziness, vertigo, leg swelling, disturbed vision, loss of coordination, and euphoria.<ref name="pmid30670513">{{cite journal |vauthors=Onakpoya IJ, Thomas ET, Lee JJ, Goldacre B, Heneghan CJ |title=Benefits and harms of pregabalin in the management of neuropathic pain: a rapid review and meta-analysis of randomised clinical trials |journal=BMJ Open |volume=9 |issue=1 |pages=e023600 |date=January 2019 |doi=10.1136/bmjopen-2018-023600 |pmc=6347863 |pmid=30670513}}</ref> It has an ] profile similar to other ] (CNS) ].<ref name="Federal Register-2005"/> Even though pregabalin is a ] and ], it can sometimes paradoxically induce ]s, particularly in large ].<ref name="Slocum-2018">{{cite journal |vauthors=Slocum GW, Schult RF, Gorodetsky RM, Wiegand TJ, Kamali M, Acquisto NM |date=January 1, 2018 |title=Pregabalin and paradoxical reaction of seizures in a large overdose |journal=Toxicology Communications |volume=2 |issue=1 |pages=19–20 |doi=10.1080/24734306.2018.1458465 |doi-access=free |s2cid=79760296}}</ref> ]s associated with the use of pregabalin include:<ref>{{cite journal | vauthors = Semel D, Murphy TK, Zlateva G, Cheung R, Emir B | title = Evaluation of the safety and efficacy of pregabalin in older patients with neuropathic pain: results from a pooled analysis of 11 clinical studies | journal = BMC Family Practice | volume = 11 | issue = 1 | pages = 85 | date = November 2010 | pmid = 21054853 | pmc = 2988717 | doi = 10.1186/1471-2296-11-85 | doi-access = free }}</ref><ref name="Pfizer Australia Pty Ltd.-2006">{{citation |publisher=Pfizer Australia Pty Ltd. |title=Lyrica (Australian Approved Product Information) |newspaper=Pfizer: The World's Largest Research-Based Pharmaceutical Company |year=2006|archive-url=https://web.archive.org/web/20180313141049/https://www.pfizer.com.au/products/lyrica |url=https://www.pfizer.com.au/products/lyrica |archive-date=March 13, 2018}}</ref><ref name="AMH2006">{{cite book |title=Australian Medicines Handbook, 2006 |publisher=Australian Medicines Handbook |year=2006 |isbn=978-0-9757919-2-9 |veditors=Rossi S}}{{page needed|date=August 2016}}</ref>
]s associated with the use of pregabalin include:<ref name="LyricaPI">Pfizer Australia Pty Ltd. Lyrica (Australian Approved Product Information). West Ryde: Pfizer; 2006.</ref><ref name="AMH2006">Rossi S, editor. ] 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3</ref>
*Very common (>10% of patients): dizziness, drowsiness * Very common (>10% of people with pregabalin): ], ].
*Common (1–10% of patients): blurred vision, ], increased ], ], confusion, vivid ]s, changes in libido (increase or decrease), irritability, ], attention changes, abnormal coordination, memory impairment, tremors, ], ], vertigo, dry mouth and constipation, vomiting and flatulence, erectile dysfunction, fatigue, peripheral ], drunkenness, abnormal walking, weight gain. * Common (1–10% of people with pregabalin): peripheral ], ], ], ] and subsequent ], ], ], vivid ]s, changes in libido (increase or decrease), ], ], attention changes, ], memory impairment, ], ], ], ], ], ], ], ], ], ], ], feelings of ], abnormal walking, ], ], increased ] level.
*Infrequent (0.1–1% of patients): depression, lethargy, agitation, hallucinations, ], ], ], ], excessive salivation, sweating, flushing, rash, muscle cramp, ], ], ], ], ], ] * Infrequent (0.1–1% of people with pregabalin): ], ], ], ], ]s, ], ], ], ], ], ], ], ], ], ], ], ], ], ], ], ].
*Rare (<0.1% of patients): ], first degree ], ], ], ], ], ], ], suicidal thoughts or behavior.<ref></ref> * Rare (<0.1% of people with pregabalin): ], first-degree ], ], ], ], ], ], ], ] or behavior.<ref name="USFDA-2011">{{cite web |date=June 2011 |title=Medication Guide (Pfizer Inc.) |publisher=U.S. ] (FDA) |url=https://www.fda.gov/downloads/Drugs/DrugSafety/UCM152825.pdf |access-date=November 6, 2011 |archive-url=https://web.archive.org/web/20110908154358/http://www.fda.gov/downloads/Drugs/DrugSafety/UCM152825.pdf |archive-date=September 8, 2011}}</ref>


Cases of recreational use, with associated adverse effects, have been reported.<ref name="Millar-2013">{{cite journal |vauthors=Millar J, Sadasivan S, Weatherup N, Lutton S |date=September 7, 2013 |title=Lyrica Nights–Recreational Pregabalin Abuse in an Urban Emergency Department |journal=Emergency Medicine Journal |volume=30 |issue=10 |pages=874.2–874 |doi=10.1136/emermed-2013-203113.20 |s2cid=73986091}}</ref>
Pregabalin may also cause withdrawal effects after long-term use if discontinued abruptly. When prescribed for seizures, quitting "cold turkey" can increase the strength of the seizures and possibly cause the seizures to reoccur. Withdrawal symptoms include restlessness, insomnia, and anxiety. Pregabalin should be reduced gradually when finishing treatment. Because of complication risk associated with certain common side-effects in patients affected by other health issues, Pregabalin should not be used without regular medical supervision and any side effect should immediately be reported. {{Citation needed|date=September 2009}}


===Overdosage=== ===Withdrawal symptoms===
Following abrupt or rapid discontinuation of pregabalin, some people reported symptoms suggestive of ]. The FDA determined that the ] profile of pregabalin, as measured by a personal ] checklist, was quantitatively less than ].<ref name="Federal Register-2005"/>
Several renal failure patients developed ] while receiving pregabalin, apparently as a result of gradual accumulation of the drug. Acute overdosage may be manifested by ], ] and ]. Plasma, serum or blood concentrations of pregabalin may be measured to monitor therapy or to confirm a diagnosis of poisoning in hospitalized patients.<ref>{{cite journal | author = Murphy NG, Mosher L. | title = Severe myoclonus from pregabalin (Lyrica) due to chronic renal insufficiency | journal = Clin. Tox. | volume = 46 | pages = 594 | year = 2008}}</ref><ref>{{cite journal | author = Yoo L, Matalon D, Hoffman RS, Goldfarb DS | title = Treatment of pregabalin toxicity by hemodialysis in a patient with kidney failure | journal = Am. J. Kidney Dis. | volume = 54 | pages = 1127–30 | year = 2009 | doi = 10.1053/j.ajkd.2009.04.014 | pmid = 19493601 | issue = 6}}</ref><ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1296-1297.</ref>
Even people who have discontinued short-term use of pregabalin have experienced ] including ], ], ], ], ], ], ], ], ], ], and ].<ref name="medicines.org.uk-2020">{{cite web |title=Lyrica Capsules |website=medicines.org.uk |url=https://www.medicines.org.uk/EMC/medicine/14651/SPC/Lyrica+Capsules/ |access-date=October 19, 2020 |url-status=live |archive-url=https://web.archive.org/web/20201020191035/https://www.medicines.org.uk/EMC/medicine/14651/SPC/Lyrica+Capsules/ |archive-date=October 20, 2020}}</ref>

===Pregnancy===
It is unclear if it is safe for use in pregnancy with some studies showing potential harm.<ref>{{cite web |title=Pregabalin Pregnancy and Breastfeeding Warnings |url=https://www.drugs.com/pregnancy/pregabalin.html |access-date=August 29, 2016 |url-status=live |archive-url=https://web.archive.org/web/20190321033634/https://www.drugs.com/pregnancy/pregabalin.html |archive-date=March 21, 2019}}</ref>

===Breathing===
In December 2019, the US ] (FDA) warned about serious breathing issues for those taking ] or pregabalin when used with ] (CNS) ] or for those with lung problems.<ref name="USFDA-2019-Serious-Breathing-Problems">{{cite web |date=December 19, 2019 |title=FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) When used with CNS depressants or in patients with lung problems |website=U.S. ] (FDA) |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin |access-date=December 21, 2019 |url-status=live |archive-url=https://web.archive.org/web/20191222091828/https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin |archive-date=December 22, 2019}} {{Source-attribution}}</ref><ref name="USFDA-2019-Serious-Breathing-Problems-PDF">{{cite web |date=December 19, 2019 |title=FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) When used with CNS depressants or in patients with lung problems |website=U.S. ] (FDA) |format=PDF |url=https://www.fda.gov/media/133681/download |url-status=live |archive-url=https://web.archive.org/web/20191222091828/https://www.fda.gov/media/133681/download |archive-date=December 22, 2019}} {{Source-attribution}}</ref>

The FDA required new warnings about the risk of respiratory depression to be added to the prescribing information of the gabapentinoids.<ref name="USFDA-2019-Serious-Breathing-Problems"/> The FDA also required the drug manufacturers to conduct clinical trials to further evaluate their abuse potential, particularly in combination with opioids, because misuse and abuse of these products together is increasing, and co-use may increase the risk of respiratory depression.<ref name="USFDA-2019-Serious-Breathing-Problems"/>

Among 49 case reports submitted to the FDA over the five-year period from 2012 to 2017, twelve people died from ] with gabapentinoids, all of whom had at least one risk factor.<ref name="USFDA-2019-Serious-Breathing-Problems"/>

The FDA reviewed the results of two randomized, double-blind, placebo-controlled clinical trials in healthy people, three observational studies, and several studies in animals.<ref name="USFDA-2019-Serious-Breathing-Problems"/> One trial showed that using pregabalin alone and using it with an opioid pain reliever can depress breathing function.<ref name="USFDA-2019-Serious-Breathing-Problems"/> The other trial showed gabapentin alone increased pauses in breathing during sleep.<ref name="USFDA-2019-Serious-Breathing-Problems"/> The three observational studies at one academic medical center showed a relationship between gabapentinoids given before surgery and respiratory depression occurring after different kinds of surgeries.<ref name="USFDA-2019-Serious-Breathing-Problems"/> The FDA also reviewed several animal studies that showed pregabalin alone and pregabalin plus opioids can depress respiratory function.<ref name="USFDA-2019-Serious-Breathing-Problems"/>

==Overdose==
An ] of pregabalin usually consists of severe ], severe ], ], ], uncontrollable jerking motions (]), and anxiety.<ref name="pmid30381161">{{cite journal |vauthors=Desai A, Kherallah Y, Szabo C, Marawar R |title=Gabapentin or pregabalin induced myoclonus: A case series and literature review |journal=Journal of Clinical Neuroscience |volume=61 |pages=225–234 |date=March 2019 |doi=10.1016/j.jocn.2018.09.019 |pmid=30381161 |s2cid=53165515}}</ref> In one case study, ]r detachment was reported with overdose<ref name="pmid30405948">{{cite journal |vauthors=Tanyıldız B, Kandemir B, Mangan MS, Tangılntız A, Göktaş E, Şimşek S |date=October 2018 |title=Bilateral Serous Macular Detachment After Attempted Suicide with Pregabalin |journal=Turkish Journal of Ophthalmology |volume=48 |issue=5 |pages=254–257 |doi=10.4274/tjo.70923 |pmc=6216534 |pmid=30405948}}</ref> Despite these symptoms an overdose is not usually fatal unless mixed with another CNS ]. Several people with ] developed ] while receiving pregabalin, apparently as a result of the gradual accumulation of the drug. Acute overdosage may be manifested by ], ], and ]. Plasma, serum, or blood concentrations of pregabalin may be measured to monitor therapy or to confirm a diagnosis of poisoning in hospitalized people.<ref name="Murphy-2008">{{cite journal |vauthors=Murphy NG, Mosher L |year=2008 |title=79. Severe myoclonus from pregabalin (Lyrica) due to chronic renal insufficiency |journal=Clinical Toxicology |volume=46 |issue=7 |page=604 |title-link=doi |doi=10.1080/15563650802255033 |doi-access=free |s2cid=218857181}}</ref><ref name="pmid19493601">{{cite journal |vauthors=Yoo L, Matalon D, Hoffman RS, Goldfarb DS |title=Treatment of pregabalin toxicity by hemodialysis in a patient with kidney failure |journal=American Journal of Kidney Diseases |volume=54 |issue=6 |pages=1127–1130 |date=December 2009 |format=PDF |citeseerx=10.1.1.955.4223 |doi=10.1053/j.ajkd.2009.04.014 |pmid=19493601 |url=http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.955.4223&rep=rep1&type=pdf |access-date=October 19, 2020 |url-status=live |archive-url=https://web.archive.org/web/20220412003441/http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.955.4223&rep=rep1&type=pdf |archive-date=April 12, 2022}}</ref><ref name="Baselt-2008">{{cite book |vauthors=Baselt RC |title=Disposition of Toxic Drugs and Chemicals in Man |publisher=Biomedical Publications |year=2008 |isbn=978-0-9626523-7-0 |edition=8th |pages=1296–1297}}</ref>

==Interactions==
No interactions have been demonstrated '']''. The manufacturer notes some potential pharmacological interactions with ]s, ]s, ]s, ] (]), and other drugs that depress the central nervous system. ]s may enhance the adverse/toxic effect of pregabalin. Pregabalin may enhance the fluid-retaining effect of certain anti-diabetic agents (]s).<ref name="Lexi-Drugs [database on the Internet-2007">{{cite web |title=Pregabalin |work=Lexi-Drugs [database on the Internet |location=Hudson (OH) |publisher=Lexi-Comp, Inc. |date=2007 |url=https://www.localhealthrx.com/drugs/pregabalin/ |access-date=October 29, 2015 |url-status=dead |archive-url=https://web.archive.org/web/20201019225603/https://www.localhealthrx.com/drugs/pregabalin/ |archive-date=October 19, 2020}}.</ref>


==Pharmacology== ==Pharmacology==
===Mechanism of action===
{{Main article|Gabapentinoid}}
Pregabalin is a ] medication, meaning drugs that chemically are ]s of ] (GABA), an ].<ref name="pmid27345098"/><ref name="pmid17222465"/><ref name="WyllieCascino2012"/><ref name="BenzonRathmell2013"/> However, pregabalin, like other gabapentinoids, does not mimic GABA or influence GABA receptors. Instead, its action requires binding to a specific site on the α<sub>2</sub>δ-1 protein and secondarily to reduce the release of excitatory neurtransmitters.<ref name="Dooley-2007" />

Pregabalin does not directly block ] (it is not a ]), as it does not bind to the ion conducting channel protein, called α1. However, '']'' studies show that pregabalin can reduce the normal traffic of calcium channels from intracellular sites (where they do not function) to membrane sites where they are functional.<ref name="AHFS2019"/><ref name="Cal2016"/>

While the mechanism of action of pregabalin is not definitively characterized, its action in animal models of pain, seizures and anxiety requires binding to the α<sub>2</sub>δ-1 protein.<ref name="Taylor-2020">{{cite journal | vauthors = Taylor CP, Harris EW | title = Analgesia with Gabapentin and Pregabalin May Involve <i>N</i>-Methyl-d-Aspartate Receptors, Neurexins, and Thrombospondins | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 374 | issue = 1 | pages = 161–174 | date = July 2020 | pmid = 32321743 | doi = 10.1124/jpet.120.266056 }}</ref> It has been found that this binding inhibits several actions of α2δ-1 and also inhibits the release of ]s. These excitatory neurotransmitters include ], ] (noradrenaline), ], ], ], and ].<ref name="Dooley-2007">{{cite journal | vauthors = Dooley DJ, Taylor CP, Donevan S, Feltner D | title = Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission | journal = Trends in Pharmacological Sciences | volume = 28 | issue = 2 | pages = 75–82 | date = February 2007 | pmid = 17222465 | doi = 10.1016/j.tips.2006.12.006 }}</ref> By inhibiting the release of these neurotransmitters, pregabalin reduces excess activity of neuron networks, which helps alleviate symptoms and provides relief for patients experiencing pain, seizures, or other related symptoms.<ref name="pmid23009881">{{cite journal | vauthors = Holsboer-Trachsler E, Prieto R | title = Effects of pregabalin on sleep in generalized anxiety disorder | journal = The International Journal of Neuropsychopharmacology | volume = 16 | issue = 4 | pages = 925–936 | date = May 2013 | pmid = 23009881 | doi = 10.1017/S1461145712000922 }}</ref>

===Pharmacodynamics=== ===Pharmacodynamics===
]
Like ], pregabalin binds to the α<sub>2</sub>δ (alpha2delta) subunit of the ] in the ]. Pregabalin decreases the release of neurotransmitters such as ], ], and ] (Australian Medicines Handbook). Pregabalin increases neuronal ] levels by producing a dose-dependent increase in ] activity.<ref>, ]</ref> Glutamic acid decarboxylase (GAD) is the enzyme that converts the excitatory neurotransmitter ] into the inhibitory GABA in a single step. For this reason, pregabalin greatly potentiates ], ] & other depressants.
]]]
There are two drug-binding α<sub>2</sub>δ subunits, ] and ], and pregabalin shows similar ] for (and hence lack of ] between) these two sites.<ref name="Cal2016"/> Pregabalin is selective in its binding to the α<sub>2</sub>δ VGCC subunits and does not bind significantly to other known drug receptors.<ref name="pmid16376147">{{cite journal |vauthors=Sills GJ |date=February 2006 |title=The mechanisms of action of gabapentin and pregabalin |journal=Current Opinion in Pharmacology |volume=6 |issue=1 |pages=108–113 |doi=10.1016/j.coph.2005.11.003 |pmid=16376147}}</ref><ref name="BenzonRathmell2013"/>

Despite the fact that pregabalin is a ],<ref name="pmid10189176">{{cite journal |vauthors=Bryans JS, Wustrow DJ |title=3-substituted GABA analogs with central nervous system activity: a review |journal=Medicinal Research Reviews |volume=19 |issue=2 |pages=149–177 |date=March 1999 |doi=10.1002/(SICI)1098-1128(199903)19:2<149::AID-MED3>3.0.CO;2-B |pmid=10189176 |s2cid=38496241}}</ref> it does not bind to ]s, does not convert into {{abbrlink|GABA|γ-aminobutyric acid}} or another ] '']'', and does not directly modulate GABA ] or ].<ref name="Uch2010" /><ref name="pmid16376147" /> There is currently no evidence that the effects of pregabalin are mediated by any mechanism other than binding to the α<sub>2</sub>δ-1 protein.<ref name="pmid16376147" /><ref name="pmid23642658">{{cite journal |vauthors=Stahl SM, Porreca F, Taylor CP, Cheung R, Thorpe AJ, Clair A |title=The diverse therapeutic actions of pregabalin: is a single mechanism responsible for several pharmacological activities? |journal=Trends in Pharmacological Sciences |volume=34 |issue=6 |pages=332–339 |date=June 2013 |doi=10.1016/j.tips.2013.04.001 |pmid=23642658}}</ref> In accordance, inhibition of α<sub>2</sub>δ-1 proteins by pregabalin appears to be responsible for its ], ], and ] effects in animal models.<ref name="pmid16376147" /><ref name="pmid23642658" />

Recently, the α<sub>2</sub>δ-1 protein has been found (independent of calcium channels) to associate directly with certain ], some ] and also with the extracellular matrix protein, ], and to modulate the function of these proteins.<ref name="Taylor-2020" /> This has been proposed to contribute to the analgesic action of pregabalin animal models and in clinical use.

The ] ]s ] and ], which closely resemble pregabalin and the other gabapentinoids in ], are apparent ligands of the α<sub>2</sub>δ VGCC subunit with similar affinity as the gabapentinoids (e.g., ]=71&nbsp;nM for <small>L</small>-isoleucine), and are present in human ] at micromolar concentrations (e.g., 12.9&nbsp;μM for <small>L</small>-leucine, 4.8&nbsp;μM for <small>L</small>-isoleucine).<ref name="pmid17222465" /> It has been theorized that they may be the endogenous ligands of the subunit and that they may ] the effects of gabapentinoids.<ref name="pmid17222465" /><ref name="pmid17403543">{{cite journal |vauthors=Davies A, Hendrich J, Van Minh AT, Wratten J, Douglas L, Dolphin AC |title=Functional biology of the alpha(2)delta subunits of voltage-gated calcium channels |journal=Trends in Pharmacological Sciences |volume=28 |issue=5 |pages=220–228 |date=May 2007 |doi=10.1016/j.tips.2007.03.005 |pmid=17403543 |url=https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Functional+biology+of+the+%CE%B12%CE%B4+subunits+of+voltage-gated+calcium+channels&btnG= |url-access=subscription |access-date=October 19, 2020 |url-status=live |archive-url=https://web.archive.org/web/20201021072722/https://scholar.google.com/scholar?hl=en&as_sdt=0,5&q=Functional+biology+of+the+%CE%B12%CE%B4+subunits+of+voltage-gated+calcium+channels&btnG= |archive-date=October 21, 2020}}</ref> In accordance, while gabapentinoids like pregabalin and gabapentin have ] affinities for the α<sub>2</sub>δ subunit, their potencies ''in vivo'' are in the low ] range, and competition for binding by endogenous <small>L</small>-amino acids has been said to likely be responsible for this discrepancy.<ref name="pmid23642658" />

Pregabalin was found to possess 6-fold higher affinity than gabapentin for α<sub>2</sub>δ subunit-containing VGCCs in one study.<ref name="pmid21897498">{{cite journal |vauthors=Baidya DK, Agarwal A, Khanna P, Arora MK |title=Pregabalin in acute and chronic pain |journal=Journal of Anaesthesiology Clinical Pharmacology |volume=27 |issue=3 |pages=307–314 |date=July 2011 |doi=10.4103/0970-9185.83672 |doi-access=free |pmc=3161452 |pmid=21897498}}</ref><ref name="McMahon-2013">{{cite book |vauthors=McMahon SB |title=Wall and Melzack's textbook of pain |date=2013 |publisher=Elsevier/Saunders |isbn=9780702040597 |edition=6th |location=Philadelphia, PA |page=515 |url=https://books.google.com/books?id=bNlvQJSqrB8C&pg=PA515}}</ref> However, another study found that pregabalin and gabapentin had similar affinities for the human recombinant α<sub>2</sub>δ-1 subunit (K<sub>i</sub>=32&nbsp;nM and 40&nbsp;nM, respectively).<ref name="pmid17126531">{{cite journal |vauthors=Taylor CP, Angelotti T, Fauman E |title=Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery |journal=Epilepsy Research |volume=73 |issue=2 |pages=137–150 |date=February 2007 |doi=10.1016/j.eplepsyres.2006.09.008 |pmid=17126531 |s2cid=54254671 |url=https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Pharmacology+and+mechanism+of+action+of+pregabalin%3A+The+calcium+channel+%CE%B12%E2%80%93%CE%B4+%28alpha2%E2%80%93delta%29+subunit+as+a+target+for+antiepileptic+drug+discovery&btnG= |url-access=subscription |access-date=October 19, 2020 |url-status=live |archive-url=https://web.archive.org/web/20201023083313/https://scholar.google.com/scholar?hl=en&as_sdt=0,5&q=Pharmacology+and+mechanism+of+action+of+pregabalin:+The+calcium+channel+%CE%B12%E2%80%93%CE%B4+(alpha2%E2%80%93delta)+subunit+as+a+target+for+antiepileptic+drug+discovery&btnG= |archive-date=October 23, 2020}}</ref> In any case, pregabalin is 2 to 4&nbsp;times more potent than gabapentin as an ]<ref name="pmid10189176" /><ref name="pmid12665421" /> and, in animals, appears to be 3 to 10&nbsp;times more potent than gabapentin as an ].<ref name="pmid10189176" /><ref name="pmid12665421">{{cite journal |vauthors=Lauria-Horner BA, Pohl RB |title=Pregabalin: a new anxiolytic |journal=Expert Opinion on Investigational Drugs |volume=12 |issue=4 |pages=663–672 |date=April 2003 |doi=10.1517/13543784.12.4.663 |pmid=12665421 |s2cid=36137322}}</ref>


===Pharmacokinetics=== ===Pharmacokinetics===
'''Absorption:''' Pregabalin is rapidly absorbed when administered on an empty stomach, with peak plasma concentrations occurring within one hour. Pregabalin oral bioavailability is estimated to be greater than or equal to 90% and is independent of dose. The rate of pregabalin absorption is decreased when given with food resulting in a decrease in Cmax by approximately 25 to 30% and a delay in Tmax to approximately 2.5 hours. Administration with food, however, has no clinically significant effect on the extent of absorption.<ref name="emea-spc">{{cite web|title=Summary of product characteristics {broken link}|url=http://www.emea.europa.eu/humandocs/PDFs/EPAR/lyrica/emea-combined-h546en.pdf|date=19 August 2009|publisher=]|accessdate=8 September 2009}}</ref>


====Absorption====
'''Distribution:''' Pregabalin has been shown to cross the ] in mice, rats, and monkeys. Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats. In humans, the ] of pregabalin for an orally administered dose is approximately 0.56 L/kg and is not bound to plasma proteins.<ref name="emea-spc" />
Pregabalin is ] from the ]s by an ] process mediated via the ] (LAT1, SLC7A5), a transporter for ]s such as ] and ].<ref name="Cal2016"/><ref name="pmid16376147"/><ref name="pmid23567998">{{cite journal |vauthors=Dickens D, Webb SD, Antonyuk S, Giannoudis A, Owen A, Rädisch S, Hasnain SS, Pirmohamed M |title=Transport of gabapentin by LAT1 (SLC7A5) |journal=Biochemical Pharmacology |volume=85 |issue=11 |pages=1672–1683 |date=June 2013 |doi=10.1016/j.bcp.2013.03.022 |pmid=23567998 |url=https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=+Transport+of+gabapentin+by+LAT1+%28SLC7A5%29+&btnG= |url-access=subscription |access-date=October 19, 2020 |url-status=live |archive-url=https://web.archive.org/web/20201021020947/https://scholar.google.com/scholar?hl=en&as_sdt=0,5&q=+Transport+of+gabapentin+by+LAT1+(SLC7A5)+&btnG= |archive-date=October 21, 2020}}</ref> Very few (less than 10&nbsp;drugs) are known to be transported by this transporter.<ref name="pmid18656534">{{cite journal |vauthors=del Amo EM, Urtti A, Yliperttula M |title=Pharmacokinetic role of L-type amino acid transporters LAT1 and LAT2 |journal=European Journal of Pharmaceutical Sciences |volume=35 |issue=3 |pages=161–174 |date=October 2008 |doi=10.1016/j.ejps.2008.06.015 |pmid=18656534}}</ref> Unlike ], which is transported solely by the LAT1,<ref name="pmid23567998"/><ref name="Bock2010">{{cite journal |vauthors=Bockbrader HN, Radulovic LL, Posvar EL, Strand JC, Alvey CW, Busch JA, Randinitis EJ, Corrigan BW, Haig GM, Boyd RA, Wesche DL |title=Clinical pharmacokinetics of pregabalin in healthy volunteers |journal=Journal of Clinical Pharmacology |volume=50 |issue=8 |pages=941–950 |date=August 2010 |doi=10.1177/0091270009352087 |pmid=20147618 |s2cid=9905501}}</ref> pregabalin seems to be transported not only by the LAT1 but also by other carriers.<ref name="Cal2016"/> The LAT1 is easily ], so the ] of gabapentin are dose-dependent, with diminished bioavailability and delayed peak levels at higher doses.<ref name="Cal2016"/> In contrast, this is not the case for pregabalin, which shows linear pharmacokinetics and no saturation of absorption.<ref name="Cal2016"/>


The ] ] of pregabalin is greater than or equal to 90% across and beyond its entire clinical dose range (75 to 600&nbsp;mg/day).<ref name="Bock2010"/> Food does not significantly influence the oral bioavailability of pregabalin.<ref name="Bock2010"/> Pregabalin is rapidly absorbed when administered on an empty stomach, with a ] (time to ]) of generally less than or equal to 1&nbsp;hour at doses of 300&nbsp;mg or less.<ref name="Cal2016"/><ref name="EMA2013">{{cite web |date=March 6, 2013 |title=Summary of product characteristics |publisher=] (EMA) |url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000546/WC500046602.pdf |access-date=May 6, 2013 |url-status=live |archive-url=https://web.archive.org/web/20180916023926/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000546/WC500046602.pdf |archive-date=September 16, 2018}}</ref> However, food has been found to substantially delay the absorption of pregabalin and to significantly reduce peak levels without affecting the bioavailability of the drug; T<sub>max</sub> values for pregabalin of 0.6&nbsp;hours in a fasted state and 3.2&nbsp;hours in a fed state (5-fold difference), and the ] is reduced by 25–31% in a fed versus fasted state.<ref name="Bock2010"/>
'''Metabolism:''' Pregabalin undergoes negligible metabolism in humans.<ref name="ADTPD">{{cite book |title=Antiepileptic Drugs to Treat Psychiatric Disorders |author=Susan L. McElroy, |page=370 }}}</ref> Approximately 98% of the radioactivity recovered in the urine was unchanged pregabalin. The major metabolite is N-methyl pregabalin.<ref name="emea-spc" />


====Distribution====
'''Excretion:''' Pregabalin is eliminated from the systemic circulation primarily by renal excretion as unchanged drug.<ref name="emea-spc" /> ] of pregabalin is 73 mL/minute.{{Verify source|date=September 2009}}
Pregabalin crosses the ] and enters the ].<ref name="pmid16376147"/> However, due to its low ],<ref name="Bock2010"/> pregabalin requires active transport across the blood–brain barrier.<ref name="pmid23567998"/><ref name="pmid16376147"/><ref name="pmid26305616">{{cite journal |vauthors=Geldenhuys WJ, Mohammad AS, Adkins CE, Lockman PR |title=Molecular determinants of blood-brain barrier permeation |journal=Therapeutic Delivery |volume=6 |issue=8 |pages=961–971 |year=2015 |doi=10.4155/tde.15.32 |pmc=4675962 |pmid=26305616}}</ref><ref name="pmid19937841">{{cite journal |vauthors=Müller CE |title=Prodrug approaches for enhancing the bioavailability of drugs with low solubility |journal=Chemistry & Biodiversity |volume=6 |issue=11 |pages=2071–2083 |date=November 2009 |doi=10.1002/cbdv.200900114 |pmid=19937841 |s2cid=32513471}}</ref> The LAT1 is highly expressed at the blood–brain barrier<ref name="pmid10518579">{{cite journal |vauthors=Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM |title=Selective expression of the large neutral amino acid transporter at the blood-brain barrier |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=96 |issue=21 |pages=12079–12084 |date=October 1999 |bibcode=1999PNAS...9612079B |title-link=doi |doi=10.1073/pnas.96.21.12079 |doi-access=free |pmc=18415 |pmid=10518579}}</ref> and transports pregabalin across into the brain.<ref name="pmid23567998"/><ref name="pmid16376147"/><ref name="pmid26305616"/><ref name="pmid19937841"/> Pregabalin has been shown to cross the ] in rats and is present in the ] of ] rats.<ref name="EMA2013"/> In humans, the ] of an orally administered dose of pregabalin is approximately 0.56&nbsp;L/kg.<ref name="EMA2013"/> Pregabalin is not significantly ]s (<1%).<ref name="Bock2010"/>


====Metabolism====
==Drug interactions==
Pregabalin undergoes little or no ].<ref name="Bock2010"/><ref name="Cal2016"/><ref name="ADTPD">{{cite book |title=Antiepileptic Drugs to Treat Psychiatric Disorders |publisher=INFRMA-HC |year=2008 |isbn=978-0-8493-8259-8 |veditors=McElroy SL, Keck PE, Post RM |editor-link1=Susan McElroy |page=370}}</ref> In experiments using ] techniques, it was revealed that approximately 98% of the ] recovered in the ] was unchanged pregabalin.<ref name="EMA2013"/> The main metabolite is ].<ref name="EMA2013"/>
No ] interactions have been demonstrated '']''. The manufacturer notes some potential ] interactions with ]s (pregabalin is synergistic with opioids in lower doses), ], ], ] (alcohol), and other drugs that depress the central nervous system.<ref name="LyricaPI" />


Pregabalin is generally safe in patients with liver ].<ref name="pmid37918778">{{cite journal |vauthors=Ma J, Björnsson ES, Chalasani N |title=The Safe Use of Analgesics in Patients with Cirrhosis: A Narrative Review |journal=Am J Med |volume=137 |issue=2 |pages=99–106 |date=February 2024 |doi=10.1016/j.amjmed.2023.10.022 |pmid=37918778 |s2cid=264888110}}</ref>
===Pregnancy===
Pregabalin has been assigned to pregnancy category C by the FDA. Animal studies have revealed increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity including lethality, growth retardation, and both nervous and reproduction system functional impairment. Animal studies have reported that pregabalin crosses the placenta and have shown an increased risk in male-mediated teratogenicity. There are no controlled data in human pregnancy. Pregabalin should only be given during pregnancy when there are no alternatives and benefit outweighs risk.<ref>{{cite web |url=http://drugsdb.eu/drug.php?d=Pregabalin&m=Southeast%20Medical%20Solutions%20Rx%20Llc&id=82ea6330-e914-4741-b642-e42203b92d17.xml |title=Pregabalin, Prescription Marketed Drugs, www.drugsdb.eu}}</ref>


==Misuse== ====Elimination====
Pregabalin is ] by the kidneys in the ], mainly in its unchanged form.<ref name="Bock2010"/><ref name="EMA2013"/> It has a relatively short ], with a reported value of 6.3&nbsp;hours.<ref name="Bock2010"/> Because of its short elimination half-life, pregabalin is administered 2 to 3&nbsp;times per day to maintain therapeutic levels.<ref name="Bock2010"/> The ] of pregabalin is 73&nbsp;mL/minute.<ref name="DailyMed-2020">{{cite web |title=Lyrica- pregabalin capsule Lyrica- pregabalin solution |website=DailyMed |date=June 15, 2020 |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=60185c88-ecfd-46f9-adb9-b97c6b00a553 |access-date=August 27, 2022 |url-status=live |archive-url=https://web.archive.org/web/20210925211707/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=60185c88-ecfd-46f9-adb9-b97c6b00a553 |archive-date=September 25, 2021}}</ref>
Pregabalin is a Schedule V drug, classified as a ]. The potential for ] of pregabalin is slightly less than the potential with ]s. It has a slowly growing number of abusers in the United States, due to the fact that it is far more potent than Gabapentin. <ref name="Chalabianloo">{{cite journal | last=Chalabianloo | first=F | coauthors=Schjøtt J | title=Pregabalin and its potential for abuse | journal=] | volume=129 | issue=3 | pages=186–187 | month=January | year=2009 | url=http://www.tidsskriftet.no/index.php?vp_SEKS_ID=1797598 | pmid=19180163 | doi=10.4045/tidsskr.08.0047 }}</ref>


==See also== ==Chemistry==
Pregabalin is a ] that is a 3-substituted ] as well as a γ-amino acid.<ref name="Wyllie_2012"/><ref name="BenzonRathmell2013"/> Because of its chemical and pharmacological similarities to gabapentin, it is sometimes called a ] drug. Specifically, pregabalin is (''S'')-(+)-3-isobutyl-GABA.<ref name="pmid18221197">{{cite journal |vauthors=Yogeeswari P, Ragavendran JV, Sriram D |title=An update on GABA analogs for CNS drug discovery |journal=Recent Patents on CNS Drug Discovery |volume=1 |issue=1 |pages=113–118 |date=January 2006 |title-link=doi |doi=10.2174/157488906775245291 |pmid=18221197}}</ref><ref name="pmid11966555">{{cite journal |vauthors=Rose MA, Kam PC |title=Gabapentin: pharmacology and its use in pain management |journal=Anaesthesia |volume=57 |issue=5 |pages=451–462 |date=May 2002 |title-link=doi |doi=10.1046/j.0003-2409.2001.02399.x |pmid=11966555 |s2cid=27431734}}</ref><ref name="WhelessWillmore2009">{{cite book |vauthors=Wheless JW, Willmore J, Brumback RA |title=Advanced Therapy in Epilepsy |publisher=PMPH-USA |year=2009 |isbn=978-1-60795-004-2 |pages=302 |url=https://books.google.com/books?id=4W7UI-FPZmoC&pg=PA302}}</ref> Pregabalin also ]s the ]s ] and ], and this may be of greater relevance in relation to its ] than its structural similarity to GABA.<ref name="pmid17222465"/><ref name="pmid17403543"/><ref name="pmid18221197"/>
* ]


==References== ===Synthesis===
] of pregabalin have been described.<ref name="VardanyanHruby2016">{{cite book |vauthors=Vardanyan R, Hruby V |title=Synthesis of Best-Seller Drugs |date=January 7, 2016 |publisher=Elsevier Science |isbn=978-0-12-411524-8 |pages=158 |url=https://books.google.com/books?id=A8oHBgAAQBAJ&pg=PA158 |access-date=June 22, 2018 |url-status=live |archive-url=https://web.archive.org/web/20210829003809/https://books.google.com/books?id=A8oHBgAAQBAJ&pg=PA158 |archive-date=August 29, 2021}}</ref><ref name="AndrushkoAndrushko2013">{{cite book |vauthors=Andrushko V, Andrushko N |title=Stereoselective Synthesis of Drugs and Natural Products |date=August 16, 2013 |publisher=John Wiley & Sons |isbn=978-1-118-62833-1 |pages=869 |url=https://books.google.com/books?id=jXFwAAAAQBAJ&pg=PA869 |access-date=June 22, 2018 |url-status=live |archive-url=https://web.archive.org/web/20210829205931/https://books.google.com/books?id=jXFwAAAAQBAJ&pg=PA869 |archive-date=August 29, 2021}}</ref>
{{reflist}}


==External links== ==History==
Pregabalin was synthesized in 1990 as an ]. It was invented by ] ] at ] in ].<ref name="Lowe-2008">{{cite web |vauthors=Lowe D |author-link=Derek Lowe (chemist) |date=March 25, 2008 |title=Getting to Lyrica |website=In the Pipeline |publisher=Science |url=https://www.science.org/content/blog-post/getting-lyrica |access-date=November 21, 2015 |url-status=live |archive-url=https://web.archive.org/web/20220827061356/https://www.science.org/content/blog-post/getting-lyrica |archive-date=August 27, 2022}}</ref> During 1988 to 1990, Ryszard Andruszkiewicz, a visiting research fellow, synthesized a series of molecules requested by Silverman.<ref name="Andruszkiewicz">{{cite journal | vauthors = Andruszkiewicz R, Silverman RB | title = 4-Amino-3-alkylbutanoic acids as substrates for gamma-aminobutyric acid aminotransferase | journal = The Journal of Biological Chemistry | volume = 265 | issue = 36 | pages = 22288–22291 | date = December 1990 | pmid = 2266125 | doi = 10.1016/S0021-9258(18)45702-X | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=2266125 | access-date = August 25, 2016 | url-status = live | title-link = doi | doi-access = free | archive-url = https://web.archive.org/web/20220827061408/https://www.jbc.org/article/S0021-9258(18)45702-X/fulltext | archive-date = August 27, 2022 }}</ref> Upon testing in mouse seizure models by collaborators at ],<ref>{{cite journal | vauthors = Silverman RB, Andruszkiewicz R, Nanavati SM, Taylor CP, Vartanian MG | title = 3-Alkyl-4-aminobutyric acids: the first class of anticonvulsant agents that activates L-glutamic acid decarboxylase | journal = Journal of Medicinal Chemistry | volume = 34 | issue = 7 | pages = 2295–2298 | date = July 1991 | pmid = 2067001 | doi = 10.1021/jm00111a053 }}</ref> one looked particularly promising. In vitro, it activated ], an enzyme, but this later proved to be unimportant to prevention of seizures. Silverman had originally hoped that the enzyme would increase the production of the inhibitory neurotransmitter GABA and block convulsions.<ref name="Merrill-2010">{{cite news |date=February 25, 2010 |title=Silverman's golden drug makes him NU's golden ticket |url=http://www.northbynorthwestern.com/story/silvermans-golden-drug-makes-him-nus-golden-ticket/ |url-status=dead |archive-url=https://web.archive.org/web/20160601194802/http://www.northbynorthwestern.com/story/silvermans-golden-drug-makes-him-nus-golden-ticket/ |archive-date=June 1, 2016 |access-date=May 19, 2016 |work=North by Northwestern |vauthors=Merrill N}}</ref> After extensive development studies and clinical trials by Parke-Davis the drug was approved in the European Union in 2004. The US received FDA approval for use in treating ], ] ], and ] in December 2004. Pregabalin then appeared on the US market under the brand name'' Lyrica'' in the fall of 2005.<ref name="pmid15959952">{{cite journal | vauthors = Dworkin RH, Kirkpatrick P | title = Pregabalin | journal = Nature Reviews. Drug Discovery | volume = 4 | issue = 6 | pages = 455–456 | date = June 2005 | pmid = 15959952 | doi = 10.1038/nrd1756 | url = https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=Fresh+from+the+pipeline%3A+Pregabalin+2005&btnG= | access-date = October 26, 2020 | url-access = subscription | url-status = live | s2cid = 265702200 | archive-url = https://web.archive.org/web/20201029175208/https://scholar.google.com/scholar?hl=en&as_sdt=0,5&q=Fresh+from+the+pipeline:+Pregabalin+2005&btnG= | archive-date = October 29, 2020 }}</ref> In 2017, the FDA approved pregabalin extended-release Lyrica CR for the management of neuropathic pain associated with diabetic peripheral neuropathy, and postherpetic neuralgia.<ref name="Seeking Alpha-2017">{{cite news |title=FDA approves LYRICA CR extended-release tablets CV |newspaper=Seeking Alpha |date=October 12, 2017 |url=https://seekingalpha.com/news/3300636-fda-approves-lyrica-cr-extended-release-tablets-cv |access-date=September 16, 2022 |url-status=live |archive-url=https://web.archive.org/web/20220920163128/https://seekingalpha.com/news/3300636-fda-approves-lyrica-cr-extended-release-tablets-cv |archive-date=September 20, 2022}}</ref> However, unlike the ] formulation, Lyrica CR was not approved for the management of ] or as add-on therapy for adults with ].<ref name="Reuters-2018">{{cite news |work=Reuters |title=BRIEF-FDA approves Pfizer's Lyrica CR extended-release tablets CV |url=https://www.reuters.com/article/brief-fda-approves-pfizers-lyrica-cr-ext/brief-fda-approves-pfizers-lyrica-cr-extended-release-tablets-cv-idUSASB0BMUS |access-date=October 3, 2018 |url-status=live |archive-url=https://web.archive.org/web/20181004021252/https://www.reuters.com/article/brief-fda-approves-pfizers-lyrica-cr-ext/brief-fda-approves-pfizers-lyrica-cr-extended-release-tablets-cv-idUSASB0BMUS |archive-date=October 4, 2018}}</ref><ref name="DailyMed-2020"/>
* http://www.webmd.com/drugs/drug-93965-Lyrica+Oral.aspx?drugid=93965&drugname=Lyrica+Oral
*
*
* {{DailyMed|5166|Lyrica (pregabalin)}}
* ] ,


==Society and culture==

===Legal status===
* United States: During clinical trials a small number of users (~4%) reported ] after use, which led to its control in the US.<ref name="Drugs.com-Lyrica-2016">{{cite web |title=Lyrica: Package Insert & Prescribing Information |website=Drugs.com |url=https://www.drugs.com/pro/lyrica.html |access-date=August 18, 2016 |url-status=live |archive-url=https://web.archive.org/web/20170813014258/https://www.drugs.com/pro/lyrica.html |archive-date=August 13, 2017}}</ref> The ] (DEA) classified pregabalin as a ] and placed pregabalin, including its salts, and all products containing pregabalin into ] of the ].<ref name="DEA Diversion Control Division-2005">{{cite web |title=2005 - Placement of Pregabalin Into Schedule V |website=DEA Diversion Control Division |date=July 28, 2005 |url=https://www.deadiversion.usdoj.gov/fed_regs/rules/2005/fr0728.htm |access-date=August 27, 2022 |url-status=live |archive-url=https://web.archive.org/web/20220528181200/https://www.deadiversion.usdoj.gov/fed_regs/rules/2005/fr0728.htm |archive-date=May 28, 2022}}</ref><ref name="Federal Register-2005">{{cite web |title=Schedules of Controlled Substances: Placement of Pregabalin Into Schedule V |website=Federal Register |date=July 28, 2005 |url=https://www.federalregister.gov/documents/2005/07/28/05-15036/schedules-of-controlled-substances-placement-of-pregabalin-into-schedule-v |access-date=August 27, 2022 |url-status=live |archive-url=https://web.archive.org/web/20210802131217/https://www.federalregister.gov/documents/2005/07/28/05-15036/schedules-of-controlled-substances-placement-of-pregabalin-into-schedule-v |archive-date=August 2, 2021}}</ref><ref name="usdoj.gov-2015">{{cite web |title=Title 21 CFR – PART 1308 – Section 1308.15 Schedule V |website=usdoj.gov |url=http://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_15.htm |access-date=September 27, 2015 |url-status=dead |archive-url=https://web.archive.org/web/20200903190235/https://www.deadiversion.usdoj.gov/21cfr/cfr/1308/1308_15.htm |archive-date=September 3, 2020}}</ref>
* Norway: Pregabalin is in prescription Schedule B, alongside ]s.<ref name="Felleskatalogen-2015">{{cite web |work=Felleskatalogen |date=May 7, 2015 |title=Lyrica |language=no |url=https://www.felleskatalogen.no/medisin/lyrica-pfizer-561166 |access-date=October 26, 2020 |url-status=dead |archive-url=https://web.archive.org/web/20161223153207/https://www.felleskatalogen.no/medisin/lyrica-pfizer-561166 |archive-date=December 23, 2016}}</ref><ref name="Chalabianloo">{{cite journal |vauthors=Chalabianloo F, Schjøtt J |title=Pregabalin og misbrukspotensial |trans-title=Pregabalin and its potential for abuse |language=no |journal=Tidsskrift for den Norske Laegeforening |volume=129 |issue=3 |pages=186–187 |date=January 2009 |title-link=doi |doi=10.4045/tidsskr.08.0047 |doi-access=free |pmid=19180163 |url=https://tidsskriftet.no/2009/01/legemidler-i-praksis/pregabalin-og-misbrukspotensial |access-date=October 26, 2020 |url-status=live |archive-url=https://web.archive.org/web/20201029162224/https://tidsskriftet.no/2009/01/legemidler-i-praksis/pregabalin-og-misbrukspotensial |archive-date=October 29, 2020}}</ref>
* United Kingdom: On January 14, 2016, the ] (ACMD) wrote a letter to Home Office ministers recommending that pregabalin alongside ] should be controlled under the ].<ref name="GOV.UK-2016">{{cite web |date=January 14, 2016 |title=Re: Pregabalin and Gabapentin advice |website=GOV.UK |url=https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/491854/ACMD_Advice_-_Pregabalin_and_gabapentin.pdf |access-date=February 6, 2019 |url-status=live |archive-url=https://web.archive.org/web/20201108101040/https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/491854/ACMD_Advice_-_Pregabalin_and_gabapentin.pdf |archive-date=November 8, 2020}}</ref><ref name="GOV.UK-2017">{{cite web |date=November 10, 2017 |title=Pregabalin and gabapentin: proposal to schedule under the Misuse of Drugs Regulations 2001 |website=GOV.UK |url=https://www.gov.uk/government/consultations/pregabalin-and-gabapentin-proposal-to-schedule-under-the-misuse-of-drugs-regulations-2001 |access-date=April 2, 2020 |url-status=live |archive-url=https://web.archive.org/web/20200103103115/https://www.gov.uk/government/consultations/pregabalin-and-gabapentin-proposal-to-schedule-under-the-misuse-of-drugs-regulations-2001 |archive-date=January 3, 2020}}</ref> It was announced in October 2018, that Pregabalin would become reclassified as a class C ] from April 2019.<ref name="pmid30327316">{{cite journal |vauthors=Mayor S |title=Pregabalin and gabapentin become controlled drugs to cut deaths from misuse |journal=BMJ |volume=363 |pages=k4364 |date=October 2018 |doi=10.1136/bmj.k4364 |pmid=30327316 |s2cid=53520780 |url=https://www.bmj.com/content/363/bmj.k4364 |url-access=subscription |access-date=February 6, 2019 |url-status=live |archive-url=https://web.archive.org/web/20190809170709/https://www.bmj.com/content/363/bmj.k4364 |archive-date=August 9, 2019}}</ref><ref name="GOV.UK-2018">{{cite web |date=October 15, 2018 |title=Pregabalin and gabapentin to be controlled as Class C drugs |website=GOV.UK |url=https://www.gov.uk/government/news/pregabalin-and-gabapentin-to-be-controlled-as-class-c-drugs |access-date=April 2, 2020 |url-status=live |archive-url=https://web.archive.org/web/20201112034051/https://www.gov.uk/government/news/pregabalin-and-gabapentin-to-be-controlled-as-class-c-drugs |archive-date=November 12, 2020}}</ref><ref name="GOV.UK-2019">{{cite web |title=Control of pregabalin and gabapentin under the Misuse of Drugs Act 1971 |website=GOV.UK |date=March 29, 2019 |url=https://www.gov.uk/government/publications/circular-0192018-control-of-pregabalin-and-gabapentin-under-the-misuse-of-drugs-act-1971/control-of-pregabalin-and-gabapentin-under-the-misuse-of-drugs-act-1971 |access-date=February 21, 2024 |url-status=live |archive-url=https://web.archive.org/web/20240221044657/https://www.gov.uk/government/publications/circular-0192018-control-of-pregabalin-and-gabapentin-under-the-misuse-of-drugs-act-1971/control-of-pregabalin-and-gabapentin-under-the-misuse-of-drugs-act-1971 |archive-date=February 21, 2024}}</ref>

In the United States, the FDA has approved pregabalin for ] for adults with partial onset ], management of ] and ] associated with ] injury and ], and the treatment of ].<ref name="Off-label">{{cite web |title=Pfizer to pay $2.3&nbsp;billion to resolve criminal and civil health care liability relating to fraudulent marketing and the payment of kickbacks |publisher=Stop Medicare Fraud, U.S. Departments of Health & Human Services, and of Justice |url=http://www.stopmedicarefraud.gov/pfizerfactsheet.html |access-date=July 4, 2012 |url-status=dead |archive-url=https://web.archive.org/web/20120830023954/http://www.stopmedicarefraud.gov/pfizerfactsheet.html |archive-date=August 30, 2012}}</ref> Pregabalin has also been approved in the European Union, the United Kingdom, and Russia for treatment of ].<ref name="Levy-2019"/><ref name="pmid17610384"/><ref name="GAD">{{cite press release |title=Pfizer's Lyrica Approved for the Treatment of Generalized Anxiety Disorder (GAD) in Europe |url=http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/03-27-2006/0004327379 |access-date=November 6, 2011 |url-status=dead |archive-url=https://web.archive.org/web/20070929121837/http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=%2Fwww%2Fstory%2F03-27-2006%2F0004327379 |archive-date=September 29, 2007}}</ref>

===Economics===
Pregabalin is available as a ] in a number of countries, including the United States as of July 2019.<ref name="BNF76"/><ref name="Generic Lyrica Availability"/><ref name="Levy-2019">{{citation |vauthors=Levy S |title=Nine generic firms get FDA approval for generic Lyrica. |work=Drug Store News |date=July 22, 2019 |url=https://www.drugstorenews.com/pharmacy/nine-generic-firms-get-fda-approval-for-generic-lyrica/ |archive-url=https://web.archive.org/web/20200805105514/https://drugstorenews.com/pharmacy/nine-generic-firms-get-fda-approval-for-generic-lyrica |archive-date=August 5, 2020}}</ref> In the United States as of July 2019 the wholesale/pharmacy cost for generic pregabalin is US$0.17–0.22 per 150&nbsp;mg capsule.<ref name="46brooklyn Research-2019">{{cite web |title=Generic Lyrica launches at 97% discount to brand version |website=46brooklyn Research |date=July 23, 2019 |url=https://www.46brooklyn.com/news/2019/7/23/lyrica-goes-generic |access-date=December 25, 2019 |url-status=live |archive-url=https://web.archive.org/web/20200716075241/https://www.46brooklyn.com/news/2019/7/23/lyrica-goes-generic |archive-date=July 16, 2020}}</ref>

From 2008 until 2018, Pfizer engaged in extensive ] campaigns to promote its branded product Lyrica for ] and diabetic nerve pain indications. In January 2016, the company spent a record amount, $24.6&nbsp;million for a single drug on TV ads, reaching global revenues of $14&nbsp;billion, more than half in the United States.<ref name="Bulik-2016">{{cite news |vauthors=Bulik BS |date=March 2016 |title=AbbVie's Humira, Pfizer's Lyrica kick off 2016 with hefty TV ad spend |work=FiercePharma |url=https://www.fiercepharma.com/marketing/abbvie-s-humira-pfizer-s-lyrica-kick-off-2016-hefty-tv-ad-spend |access-date=March 5, 2017 |archive-url=https://web.archive.org/web/20201029161332/https://www.fiercepharma.com/marketing/abbvie-s-humira-pfizer-s-lyrica-kick-off-2016-hefty-tv-ad-spend |archive-date=October 29, 2020}}</ref>

Up until 2009, Pfizer promoted Lyrica for other uses that had not been approved by medical regulators. For Lyrica and three other drugs, Pfizer was fined a record amount of US$2.3 ] by the Department of Justice,<ref name="NYT Pfizer Pays">{{cite news |vauthors=Harris G |date=September 2, 2009 |title=Pfizer Pays $2.3 Billion to Settle Marketing Case |work=] |url=https://www.nytimes.com/2009/09/03/business/03health.html |access-date=December 21, 2017 |url-status=live |archive-url=https://web.archive.org/web/20200926003914/https://www.nytimes.com/2009/09/03/business/03health.html |archive-date=September 26, 2020}}</ref><ref name="BBC-News-Prizer-Fraud-Fine-2009">{{cite web |date=September 2, 2009 |title=Pfizer agrees record fraud fine |website=] |url=http://news.bbc.co.uk/2/hi/business/8234533.stm |access-date=December 21, 2017 |url-status=live |archive-url=https://web.archive.org/web/20090908011344/http://news.bbc.co.uk/2/hi/business/8234533.stm |archive-date=September 8, 2009}}</ref><ref name="U.S. Securities and Exchange Commission-2010">{{cite web |date=2010 |title=Portions of the Pfizer Inc. 2010 Financial Report |website=] |url=https://www.sec.gov/Archives/edgar/data/78003/000119312511048877/dex13.htm |access-date=December 21, 2017 |url-status=live |archive-url=https://web.archive.org/web/20190610193252/https://www.sec.gov/Archives/edgar/data/78003/000119312511048877/dex13.htm |archive-date=June 10, 2019}}</ref> after pleading guilty to advertising and branding "with the intent to defraud or mislead". Pfizer illegally promoted the drugs, with doctors "invited to consultant meetings, many in resort locations; attendees expenses were paid; they received a fee just for being there", according to prosecutor Michael Loucks.<ref name="NYT Pfizer Pays"/><ref name="BBC-News-Prizer-Fraud-Fine-2009"/>

===Intellectual property===
Professor Richard "Rick" Silverman of Northwestern University developed pregabalin there. The university holds a patent on it, exclusively licensed to Pfizer.<ref name="Jacoby-2008">{{cite journal |vauthors=Jacoby M |year=2008 |title=Financial Windfall from Lyrica |journal=Chemical & Engineering News |volume=86 |issue=10 |pages=56–61 |doi=10.1021/cen-v086n010.p056 |url=https://cen.acs.org/articles/86/i10/Financial-Windfall-Lyrica.html |url-access=subscription |access-date=October 26, 2020 |url-status=live |archive-url=https://web.archive.org/web/20201026170423/https://cen.acs.org/articles/86/i10/Financial-Windfall-Lyrica.html |archive-date=October 26, 2020}}</ref><ref name="mw-2001">{{cite patent |country=US |number=6197819B1 |inventor=Silverman RB, Andruszkiewicz R |assign1=Northwestern University |gdate=March 6, 2001 |title=Gamma amino butyric acid analogs and optical isomers |url=https://patents.google.com/patent/US6197819B1/en}} {{Webarchive|url=https://web.archive.org/web/20190321033355/https://patents.google.com/patent/US6197819B1/en |date=March 21, 2019}}</ref> That patent, along with others, was challenged by generic manufacturers and was upheld in 2014, giving Pfizer exclusivity for Lyrica in the US until 2018.<ref name="Decker-2014">{{cite news |vauthors=Decker S |date=February 6, 2014 |title=Pfizer Wins Ruling to Block Generic Lyrica Until 2018 |work=Bloomberg |url=https://www.bloomberg.com/news/2014-02-06/pfizer-wins-ruling-to-block-generic-lyrica-until-2018.html |access-date=October 26, 2020 |url-status=live |archive-url=https://web.archive.org/web/20140208151103/https://www.bloomberg.com/news/2014-02-06/pfizer-wins-ruling-to-block-generic-lyrica-until-2018.html |archive-date=February 8, 2014}}</ref><ref name="Decision-2020">{{cite web |title=Decision: Pfizer Inc. (PFE) v. Teva Pharmaceuticals USA Inc., 12-1576, U.S. Court of Appeals for the Federal Circuit (Washington) |url=https://www.finnegan.com/files/Publication/48de9f25-b22f-4d07-9c56-151fa117073b/Presentation/PublicationAttachment/67b8c48d-5c6b-48ef-b29d-160d7303d9fa/12-1576%202-6-14.pdf |access-date=October 26, 2020 |url-status=live |archive-url=https://web.archive.org/web/20201029163458/https://www.finnegan.com/files/Publication/48de9f25-b22f-4d07-9c56-151fa117073b/Presentation/PublicationAttachment/67b8c48d-5c6b-48ef-b29d-160d7303d9fa/12-1576%202-6-14.pdf |archive-date=October 29, 2020}}</ref>

Pfizer's main patent for Lyrica, for seizure disorders, in the UK expired in 2013. In November 2018, the ] ruled that ]'s second patent on the drug, for the treatment of pain, was invalid because there was a lack of evidence for the conditions it covered – central and peripheral neuropathic pain. From October 2015, GPs were forced to change people from generic pregabalin to branded until the second patent ran out in July 2017. This cost the NHS £502 million.<ref name="Pfizer-2018">{{cite news |date=November 14, 2018 |title=Pfizer's failed pregabalin patent appeal means NHS could reclaim £502m |publisher=Pulse |url=https://www.pulsetoday.co.uk/news/politics/pfizers-failed-pregabalin-patent-appeal-means-nhs-could-reclaim-502m/ |access-date=May 17, 2024 |archive-url=https://web.archive.org/web/20181115195322/http://www.pulsetoday.co.uk/clinical/clinical-specialties/prescribing/pfizers-failed-pregabalin-patent-appeal-means-nhs-could-reclaim-502m/20037790.article |archive-date=November 15, 2018}}</ref>

===Brand names===
As of October 2017, pregabalin is marketed under many brand names: Algerika, Alivax, Alyse, Alzain, Andogablin, Aprion, Averopreg, Axual, Balifibro, Brieka, Clasica, Convugabalin, Dapapalin, Dismedox, Dolgenal, Dolica, Dragonor, Ecubalin, Epica, Epiron, Gaba-P, Gabanext, Gabarol, Gabica, Gablin, Gablovac, Gabrika, Gavin, Gialtyn, Glonervya, Helimon, Hexgabalin, Irenypathic, Kabian, Kemirica, Kineptia, Lecaent, Lingabat, Linprel, Lyribastad, Lyric, Lyrica, Lyrineur, Lyrolin, Lyzalon, Martesia, Maxgalin, Mystika, Neuragabalin, Neugaba, Neurega, Neurica, Neuristan, Neurolin, Neurovan, Neurum, Newrica, Nuramed, Paden, Pagadin, Pagamax, Painica, Pevesca, PG, Plenica, Pragiola, Prebalin, Prebanal, Prebel, Prebictal, Prebien, Prefaxil, Pregaba, Pregabalin, Pregabalina, Pregabaline, Prégabaline, Pregabalinum, Pregabateg, Pregaben, Pregabid, Pregabin, Pregacent, Pregadel, Pregagamma, Pregalex, Pregalin, Pregalodos, Pregamid, Pregan, Preganerve, Pregastar, Pregatrend, Pregavalex, Pregdin Apex, Pregeb, Pregobin, Prejunate, Prelin, Preludyo, Prelyx, Premilin, Preneurolin, Prestat, Pretor, Priga, Provelyn, Regapen, Resenz, Rewisca, Serigabtin, Symra, Vronogabic, Xablin, and Xil.<ref name="brands">{{cite web |title=Pregabalin international brands |website=Drugs.com |url=https://www.drugs.com/international/pregabalin.html |access-date=October 27, 2017 |url-status=live |archive-url=https://web.archive.org/web/20190828172817/https://www.drugs.com/international/pregabalin.html |archive-date=August 28, 2019}}</ref>

It is marketed as a ] with ] under the brand names Agemax-P, Alphamix-PG, Freenerve-P, Gaben, Macraberin-P, Mecoblend-P, Mecozen-PG, Meex-PG, Methylnuron-P, Nervolin, Nervopreg, Neurica-M, Neuroprime-PG, Neutron-OD, Nuroday-P, Nurodon-PG, Nuwin-P, Pecomin-PG, Prebel-M, Predic-GM, Pregacent-M, Pregamet, Preganerv-M, Pregeb-M OD, Pregmic, Prejunate Plus, Preneurolin Plus, Pretek-GM, Rejusite, Renerve-P, Safyvit-PR, Vitcobin-P, and Voltanerv with Methylcobalamin and ALA by Cogentrix Pharma.<ref name="brands"/>

In the US, Lyrica is marketed by ] after Upjohn was spun off from Pfizer.<ref>{{cite web | title=Pfizer Completes Transaction to Combine Its Upjohn Business with Mylan | publisher=Pfizer | via=Business Wire | date=November 16, 2020 | url=https://www.businesswire.com/news/home/20201116005378/en/ | access-date=June 17, 2024}}</ref><ref>{{cite web | title=Lyrica | website=Pfizer | url=https://www.pfizer.com/products/product-detail/lyrica | access-date=June 17, 2024}}</ref><ref>{{cite web | title=Brands | website=Viatris | date=November 16, 2020 | url=https://www.viatris.com/en/products/brands | access-date=June 17, 2024}}</ref>

==References==
{{Reflist}}

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