Array ( [0] => {{Short description|Antiplatelet medication}} [1] => {{Distinguish|Clopidol}} [2] => {{Use dmy dates|date=October 2021}} [3] => {{cs1 config |name-list-style=vanc |display-authors=6}} [4] => {{Infobox drug [5] => | verifiedrevid = 460044539 [6] => | image = Clopidogrel skeletal formula.svg [7] => | width = 200 [8] => | alt = Skeletal formula [9] => | image2 = Clopidogrel molecule ball from xtal.png [10] => | width2 = 200 [11] => | alt2 = Ball-and-stick model clopidogrel [12] => | caption = [13] => [14] => [15] => | pronounce = {{IPAc-en|k|l|ə|ˈ|p|ɪ|d|ə|ɡ|r|ɛ|l|,_|k|l|oʊ|-}}{{cite web |title=Clopidogrel |url=https://www.lexico.com/en/definition/clopidogrel |website=Lexico Dictionaries |access-date=26 October 2019 |archive-date=25 October 2019 |archive-url=https://web.archive.org/web/20191025164606/https://www.lexico.com/en/definition/clopidogrel |url-status=dead }} [16] => | tradename = Plavix, Iscover, others [17] => | Drugs.com = {{drugs.com|monograph|clopidogrel}} [18] => | MedlinePlus = a601040 [19] => | DailyMedID = Clopidogrel [20] => | pregnancy_AU = B1 [21] => | pregnancy_AU_comment = [22] => | pregnancy_category = [23] => | routes_of_administration = [[Oral administration|By mouth]] [24] => | class = [25] => | ATCvet = [26] => | ATC_prefix = B01 [27] => | ATC_suffix = AC04 [28] => | ATC_supplemental = [29] => [30] => [31] => | legal_AU = S4 [32] => | legal_AU_comment = [33] => | legal_BR = [34] => | legal_BR_comment = [35] => | legal_CA = [36] => | legal_CA_comment = [37] => | legal_DE = [38] => | legal_DE_comment = [39] => | legal_NZ = [40] => | legal_NZ_comment = [41] => | legal_UK = POM [42] => | legal_UK_comment = {{cite web | title=Plavix Summary of Product Characteristics (SmPC) | website=(emc) | date=23 January 2023 | url=https://www.medicines.org.uk/emc/product/5935/smpc | access-date=15 January 2024}} [43] => | legal_US = Rx-only [44] => | legal_US_comment = {{cite web | title=Plavix- clopidogrel tablet, film coated | website=DailyMed | date=22 September 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de8b0b67-eb25-4684-83b5-7ad785314227 | access-date=15 January 2024}} [45] => | legal_EU = Rx-only [46] => | legal_EU_comment = {{cite web | title=Plavix EPAR | website=[[European Medicines Agency]] (EMA) | date=14 July 1998 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/plavix | access-date=15 January 2024}} [47] => | legal_UN = [48] => | legal_UN_comment = [49] => | legal_status = [50] => [51] => [52] => | bioavailability = >50% [53] => | protein_bound = 94–98% [54] => | metabolism = [[Liver]] [55] => | metabolites = [56] => | onset = 2 hours [57] => | elimination_half-life = 7–8 hours (inactive metabolite) [58] => | duration_of_action = 5 days [59] => | excretion = 50% [[Kidney]]
46% [[bile duct]] [60] => [61] => [62] => | CAS_number_Ref = {{cascite|correct|??}} [63] => | CAS_number = 113665-84-2 [64] => | CAS_supplemental = [65] => | PubChem = 60606 [66] => | IUPHAR_ligand = 7150 [67] => | DrugBank_Ref = {{drugbankcite|correct|drugbank}} [68] => | DrugBank = DB00758 [69] => | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} [70] => | ChemSpiderID = 54632 [71] => | UNII_Ref = {{fdacite|correct|FDA}} [72] => | UNII = A74586SNO7 [73] => | KEGG_Ref = {{keggcite|correct|kegg}} [74] => | KEGG = D07729 [75] => | KEGG2_Ref = {{keggcite|correct|kegg}} [76] => | KEGG2 = D00769 [77] => | ChEBI_Ref = {{ebicite|correct|EBI}} [78] => | ChEBI = 37941 [79] => | ChEMBL_Ref = {{ebicite|correct|EBI}} [80] => | ChEMBL = 1771 [81] => | NIAID_ChemDB = [82] => | PDB_ligand = CGE [83] => | synonyms = [84] => [85] => [86] => | IUPAC_name = (+)-(''S'')-methyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-''c'']pyridin-5(4''H'')-yl)acetate [87] => | C=16 | H=16 | Cl=1 | N=1 | O=2 | S=1 [88] => | SMILES = COC(=O)[C@H](c1ccccc1Cl)N2CCc3c(ccs3)C2 [89] => | StdInChI_Ref = {{stdinchicite|correct|chemspider}} [90] => | StdInChI = 1S/C16H16ClNO2S/c1-20-16(19)15(12-4-2-3-5-13(12)17)18-8-6-14-11(10-18)7-9-21-14/h2-5,7,9,15H,6,8,10H2,1H3/t15-/m0/s1 [91] => | StdInChI_comment = [92] => | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} [93] => | StdInChIKey = GKTWGGQPFAXNFI-HNNXBMFYSA-N [94] => | density = [95] => | density_notes = [96] => | melting_point = [97] => | melting_high = [98] => | melting_notes = [99] => | boiling_point = [100] => | boiling_notes = [101] => | solubility = [102] => | sol_units = [103] => | specific_rotation = [104] => }} [105] => [106] => [107] => '''Clopidogrel''', sold under the brand name '''Plavix''' among others, is an [[antiplatelet drug|antiplatelet medication]] used to reduce the risk of [[Cardiovascular disease|heart disease]] and [[stroke]] in those at high risk. It is also used together with [[aspirin]] in [[myocardial infarction|heart attack]]s and following the placement of a [[Coronary stent|coronary artery stent]] ([[management of acute coronary syndrome#Antiplatelet drugs|dual antiplatelet therapy]]). It is taken [[Oral administration|by mouth]]. Its effect starts about two hours after intake and lasts for five days.{{cite web|title=Clopidogrel Bisulfate|url=https://www.drugs.com/monograph/clopidogrel-bisulfate.html|publisher=The American Society of Health-System Pharmacists|access-date=8 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221010729/https://www.drugs.com/monograph/clopidogrel-bisulfate.html|archive-date=21 December 2016}} [108] => [109] => [110] => Common side effects include headache, [[nausea]], easy bruising, itching, and [[heartburn]]. More severe side effects include [[bleeding]] and [[thrombotic thrombocytopenic purpura]]. While there is no evidence of harm from use during [[pregnancy]], such use has not been well studied.{{cite web|title=Clopidogrel (Plavix) Use During Pregnancy|url=https://www.drugs.com/pregnancy/clopidogrel.html|website=Drugs.com|access-date=14 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161221010752/https://www.drugs.com/pregnancy/clopidogrel.html|archive-date=21 December 2016}} Clopidogrel is in the [[thienopyridine]]-class of antiplatelets. It works by irreversibly inhibiting a receptor called [[P2Y12|P2Y12]] on [[platelet]]s. [111] => [112] => [113] => Clopidogrel was patented in 1982, and approved for medical use in 1997.{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=9783527607495|page=453|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA453|url-status=live|archive-url=https://web.archive.org/web/20161220130738/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA453|archive-date=20 December 2016}} It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }} In 2021, it was the 37th most commonly prescribed medication in the United States, with more than 16{{nbsp}}million prescriptions.{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}{{cite web | title=Clopidogrel - Drug Usage Statistics | website=ClinCalc | url=https://clincalc.com/DrugStats/Drugs/Clopidogrel | access-date=14 January 2024 }} It is available as a [[generic medication]]. [114] => [115] => == Medical uses == [116] => Clopidogrel is used to prevent heart attack and stroke in people who are at high risk of these events, including those with a history of myocardial infarction and other forms of [[acute coronary syndrome]], stroke, and those with [[peripheral artery disease]]. [117] => [118] => Treatment with clopidogrel or a related drug is recommended by the [[American Heart Association]] and the [[American College of Cardiology]] for people who: [119] => * Present for treatment with a myocardial infarction with [[ST elevation|ST-elevation]]{{cite journal | vauthors=O'Gara PT, Kushner FG, Ascheim DD, Casey DE, Chung MK, de Lemos JA, Ettinger SM, Fang JC, Fesmire FM, Franklin BA, Granger CB, Krumholz HM, Linderbaum JA, Morrow DA, Newby LK, Ornato JP, Ou N, Radford MJ, Tamis-Holland JE, Tommaso CL, Tracy CM, Woo YJ, Zhao DX | title = 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines | journal = J. Am. Coll. Cardiol. | volume = 61 | issue = 4 | pages = e78–140 | date = January 2013 | pmid = 23256914 | doi = 10.1016/j.jacc.2012.11.019 | doi-access = free | title-link = doi }} including [120] => :* A [[loading dose]] given in advance of [[percutaneous coronary intervention]] (PCI), followed by a full year of treatment for those receiving a vascular stent [121] => :* A loading dose given in advance of [[Fibrinolysis|fibrinolytic]] therapy, continued for at least 14 days [122] => * Present for treatment of a non-ST elevation myocardial infarction or [[unstable angina]]{{cite journal |vauthors=Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE, Ettinger SM, Fesmire FM, Ganiats TG, Lincoff AM, Peterson ED, Philippides GJ, Theroux P, Wenger NK, Zidar JP, Anderson JL | title = 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/Non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines | journal = Circulation | volume = 126 | issue = 7 | pages = 875–910 | date = August 2012 | pmid = 22800849 | doi = 10.1161/CIR.0b013e318256f1e0 | doi-access = free | title-link = doi }} [123] => :* Including a loading dose and maintenance therapy in those receiving PCI and unable to tolerate aspirin therapy [124] => :* Maintenance therapy for up to 12 months in those at medium to high risk for which a noninvasive treatment strategy is chosen [125] => * In those with stable ischemic heart disease, treatment with clopidogrel is described as a "reasonable" option for monotherapy in those who cannot tolerate aspirin, as is treatment with clopidogrel in combination with aspirin in certain high risk patients.{{cite journal |vauthors=Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, Douglas PS, Foody JM, Gerber TC, Hinderliter AL, King SB, Kligfield PD, Krumholz HM, Kwong RY, Lim MJ, Linderbaum JA, Mack MJ, Munger MA, Prager RL, Sabik JF, Shaw LJ, Sikkema JD, Smith CR, Smith SC, Spertus JA, Williams SV | title = 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons | journal = Circulation | volume = 126 | issue = 25 | pages = 3097–137 | date = December 2012 | pmid = 23166210 | doi = 10.1161/CIR.0b013e3182776f83 | doi-access = free | title-link = doi }} [126] => [127] => It is also used, along with [[acetylsalicylic acid]] (ASA, aspirin), for the prevention of [[thrombosis]] after placement of a [[coronary stent]]Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006. {{ISBN|0-9757919-2-3}} or as an alternative antiplatelet drug for people intolerant to aspirin.Michael D Randall; Karen E Neil (2004). Disease management. 2nd ed. London: Pharmaceutical Press. 159. It is available as a fixed-dose combination with aspirin.{{cite web | title=DuoPlavin EPAR | website=[[European Medicines Agency]] (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/duoplavin-0 | access-date=21 August 2020 | archive-date=4 September 2020 | archive-url=https://web.archive.org/web/20200904203651/https://www.ema.europa.eu/en/medicines/human/EPAR/duoplavin-0 | url-status=live }} [128] => [129] => A meta-analysis found clopidogrel's benefit as an antiplatelet drug in reducing cardiovascular death, myocardial infarction, and stroke to be 25% benefit in smokers, with little (8%) benefit in non-smokers.{{cite journal |vauthors=Gagne JJ, Bykov K, Choudhry NK, Toomey TJ, Connolly JG, Avorn J | title = Effect of smoking on comparative efficacy of antiplatelet agents: systematic review, meta-analysis, and indirect comparison. | journal = BMJ (Clinical Research Ed.) | volume = 347 | pages = f5307 | date = 17 September 2013 | pmid = 24046285 | doi = 10.1136/bmj.f5307 | doi-access = free | title-link = doi | pmc=3775704 }} [130] => [131] => Consensus-based therapeutic guidelines also recommend the use of clopidogrel rather than aspirin (ASA) for antiplatelet therapy in people with a history of gastric ulceration, as inhibition of the synthesis of prostaglandins by ASA can exacerbate this condition. In people with healed ASA-induced ulcers, however, those receiving ASA plus the [[proton-pump inhibitor]] (PPI) [[esomeprazole]] had a lower incidence of recurrent ulcer bleeding than those receiving clopidogrel.{{cite journal |vauthors=Chan FK, Ching JY, Hung LC, Wong VW, Leung VK, Kung NN, Hui AJ, Wu JC, Leung WK, Lee VW, Lee KK, Lee YT, Lau JY, To KF, Chan HL, Chung SC, Sung JJ | title = Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding | journal = N. Engl. J. Med. | volume = 352 | issue = 3 | pages = 238–44 | year = 2005 | pmid = 15659723 | doi = 10.1056/NEJMoa042087 | doi-access = free | title-link = doi }} However, prophylaxis with proton-pump inhibitors along with clopidogrel following acute coronary syndrome may increase adverse cardiac outcomes, possibly due to inhibition of [[CYP2C19]], which is required for the conversion of clopidogrel to its active form.{{cite journal |vauthors=Mistry SD, Trivedi HR, Parmar DM, Dalvi PS, Jiyo C | title = Impact of proton pump inhibitors on efficacy of clopidogrel: Review of evidence | journal = [[Indian Journal of Pharmacology]] | volume = 43 | issue = 2 | pages = 183–6 | year = 2011 | pmid = 21572655 | pmc = 3081459 | doi = 10.4103/0253-7613.77360 | doi-access = free | title-link = doi }}{{cite journal |vauthors=Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, Rumsfeld JS | title = Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome | journal = [[Journal of the American Medical Association]] | volume = 301 | issue = 9 | pages = 937–44 | year = 2009 | pmid = 19258584 | doi = 10.1001/jama.2009.261 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Stockl KM, Le L, Zakharyan A, Harada AS, Solow BK, Addiego JE, Ramsey S | title = Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor | journal = Arch Intern Med | volume = 170 | issue = 8 | pages = 704–10 | date = April 2010 | pmid = 20421557 | doi = 10.1001/archinternmed.2010.34 | url = http://archinte.jamanetwork.com/pdfaccess.ashx?ResourceID=593382 | issn = 1538-3679 | format = PDF | url-status = live | archive-url = https://web.archive.org/web/20160304051435/http://archinte.jamanetwork.com/pdfaccess.ashx?ResourceID=593382 | archive-date = 4 March 2016 | doi-access = free | title-link = doi }} The [[European Medicines Agency]] has issued a public statement on a possible interaction between clopidogrel and proton-pump inhibitors.{{cite web| vauthors = Wathion N |title=Public statement on possible interaction between clopidogrel and proton pump inhibitors |url= http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2009/11/WC500014409.pdf |access-date=31 March 2011|url-status=live|archive-url=https://web.archive.org/web/20110206091429/http://www.ema.europa.eu/docs/en_GB/document_library/Public_statement/2009/11/WC500014409.pdf|archive-date=6 February 2011}} However, several cardiologists have voiced concern that the studies on which these warnings are based have many limitations and that it is not certain whether an interaction between clopidogrel and proton-pump inhibitors is real.{{cite web| vauthors = Hughes S |title=EMEA issues warning on possible clopidogrel-PPI interaction, but is there really a problem?|url=http://www.theheart.org/article/980779.do|access-date=31 March 2011|archive-date=22 May 2013|archive-url=https://web.archive.org/web/20130522133251/http://www.theheart.org/article/980779.do|url-status=live}} [132] => [133] => == Adverse effects == [134] => Serious [[adverse drug reaction]]s associated with clopidogrel therapy include: [135] => [136] => * [[Thrombotic thrombocytopenic purpura]] (incidence: four per million patients treated){{cite journal | vauthors = Zakarija A, Bandarenko N, Pandey DK, Auerbach A, Raisch DW, Kim B, Kwaan HC, McKoy JM, Schmitt BP, Davidson CJ, Yarnold PR, Gorelick PB, Bennett CL | title = Clopidogrel-Associated TTP An Update of Pharmacovigilance Efforts Conducted by Independent Researchers, Pharmaceutical Suppliers, and the Food and Drug Administration | journal = Stroke | volume = 35 | issue = 2 | pages = 533–8 | year = 2004 | pmid = 14707231 | doi = 10.1161/01.STR.0000109253.66918.5E | doi-access = free | title-link = doi }}{{cite web | title=Plavix- clopidogrel bisulfate tablet, film coated | website=DailyMed | date=17 May 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=01b14603-8f29-4fa3-8d7e-9d523f802e0b | access-date=26 December 2019 | publisher=Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership | archive-date=4 August 2020 | archive-url=https://web.archive.org/web/20200804222235/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=01b14603-8f29-4fa3-8d7e-9d523f802e0b | url-status=live }} [137] => * [[Hemorrhage]] – the annual incidence of hemorrhage may be increased by the coadministration of [[aspirin]].{{cite journal |vauthors=Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias-Guiu J, Rupprecht HJ | title = Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial | journal = [[The Lancet]] | volume = 364 | issue = 9431 | pages = 331–7 | year = 2004 | pmid = 15276392 | doi = 10.1016/S0140-6736(04)16721-4 | s2cid = 9874277 }} [138] => [139] => In the CURE trial, people with acute coronary syndrome without [[ST elevation]] were treated with aspirin plus either clopidogrel or placebo and followed for up to one year. The following rates of major bleed were seen: [140] => * Any major bleeding: clopidogrel 3.7%, placebo 2.7% [141] => * Life-threatening bleeding: clopidogrel 2.2%, placebo 1.8% [142] => * Hemorrhagic stroke: clopidogrel 0.1%, placebo 0.1% [143] => [144] => The CAPRIE trial compared clopidogrel monotherapy to aspirin monotherapy for 1.6 years in people who had recently experienced a stroke or heart attack. In this trial the following rates of bleeding were observed. [145] => * Gastrointestinal hemorrhage: clopidogrel 2.0%, aspirin 2.7% [146] => * Intracranial bleeding: clopidogrel 0.4%, aspirin 0.5% [147] => [148] => In CAPRIE, itching was the only adverse effect seen more frequently with clopidogrel than aspirin. In CURE, there was no difference in the rate of non-bleeding adverse events. [149] => [150] => [[Rashes]] and itching were uncommon in studies (between 0.1 and 1% of people); serious [[hypersensitivity]] reactions are rare. [151] => [152] => == Interactions == [153] => Clopidogrel generally has a low potential to interact with other pharmaceutical drugs. Combination with other drugs that affect blood clotting, such as [[aspirin]], [[heparin]]s and [[thrombolytic drug|thrombolytic]]s, showed no relevant interactions. [[Naproxen]] did increase the likelihood of [[occult bleeding|occult]] [[gastrointestinal bleeding]], as might be the case with other [[nonsteroidal anti-inflammatory drug]]s. As clopidogrel is metabolized by the liver enzyme [[CYP2C19]], in cellular models it has been theorized that it might increase blood plasma levels of other drugs that are metabolized by this enzyme, such as [[phenytoin]] and [[tolbutamide]]. Clinical studies showed that this mechanism is irrelevant for practical purposes.{{cite book|title=Austria-Codex|editor=Jasek, W|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2007|edition=62nd|isbn=978-3-85200-181-4|pages=6526–7|language=de}} [154] => [155] => In November 2009, the US [[Food and Drug Administration]] (FDA) announced that clopidogrel should be used with caution in people using the [[proton-pump inhibitor]]s [[omeprazole]] or [[esomeprazole]],{{cite web | title=FDA Warns Plavix Patients of Drug Interactions | vauthors = DeNoon DJ | website=WebMD | date=23 February 2016 | url=http://www.webmd.com/heart-disease/news/20091117/fda-warns-plavix-patients-drug-interactions | archive-url=https://web.archive.org/web/20160223165743/http://www.webmd.com/heart-disease/news/20091117/fda-warns-plavix-patients-drug-interactions | archive-date=23 February 2016 | url-status=dead | access-date=23 November 2009 }}{{cite web| url = https://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm190825.htm| archive-url =https://web.archive.org/web/20091229162205/https://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm190825.htm | archive-date = 29 December 2009| title = Public Health Advisory: Updated Safety Information about a drug interaction between Clopidogrel Bisulfate (marketed as Plavix) and Omeprazole (marketed as Prilosec and Prilosec OTC)| publisher = [[Food and Drug Administration]] (FDA)| date = 17 November 2009| access-date = 13 March 2010 | url-status=dead }}{{cite journal |vauthors=Farhat N, Haddad N, Crispo J, Birkett N, McNair D, Momoli F, Wen SW, Mattison DR, Krewski D |title=Trends in concomitant clopidogrel and proton pump inhibitor treatment among ACS inpatients, 2000-2016 |journal=Eur. J. Clin. Pharmacol. |volume=75 |issue=2 |pages=227–235 |date=February 2019 |pmid=30324301 |doi=10.1007/s00228-018-2564-8 | s2cid=53085923 }} but [[pantoprazole]] appears to be safe.{{cite journal |vauthors=Wedemeyer RS, Blume H | title = Pharmacokinetic Drug Interaction Profiles of Proton Pump Inhibitors: An Update | journal = Drug Safety | volume = 37 | issue = 4 | pages = 201–11 | year = 2014 | pmid = 24550106 | doi = 10.1007/s40264-014-0144-0 | pmc=3975086}} The newer antiplatelet agent [[prasugrel]] has minimal interaction with {{not a typo|(es)omeprazole}}, hence might be a better antiplatelet agent (if no other contraindications are present) in people who are on these proton-pump inhibitors.{{cite journal |vauthors=John J, Koshy SK | title = Current Oral Antiplatelets: Focus Update on Prasugrel | journal = The Journal of the American Board of Family Medicine| volume = 25 | issue = 3 | pages = 343–349 | year = 2012 | pmid = 22570398 | doi = 10.3122/jabfm.2012.03.100270 | doi-access = free | title-link = doi }} [156] => [157] => == Pharmacology == [158] => Clopidogrel is a [[prodrug]] which is metabolized by the [[liver]] into its active form. The active form specifically and irreversibly inhibits the [[P2Y12|P2Y12]] subtype of [[ADP receptor]], which is important in activation of platelets and eventual cross-linking by the protein [[fibrin]]. [159] => [160] => === Pharmacokinetics and metabolism === [161] => [[File:Clopidogrel activation.svg|right|thumb|upright=1.5|Clopidogrel (top left) being activated: The first step is an oxidation mediated (mainly) by the enzyme [[CYP2C19]], unlike the activation of the related drug prasugrel. The two structures at the bottom are [[tautomer]]s of each other; and the final step is a hydrolysis. The active metabolite (top right) has [[E-Z notation|''Z'' configuration]] at the double bond C3–C16 and possibly [[Chirality (chemistry)#By configuration: R- and S-|''R'' configuration]] at the newly asymmetric C4. [162] => {{cite journal| vauthors = Pereillo JM, Maftouh M, Andrieu A, Uzabiaga MF, Fedeli O, Savi P, Pascal M, Herbert JM, Maffrand JP, Picard C| year = 2002| title = Structure and stereochemistry of the active metabolite of clopidogrel| journal = Drug Metab. Dispos.| volume = 30| issue = 11| pages = 1288–95| pmid = 12386137| doi = 10.1124/dmd.30.11.1288| s2cid = 2493588 }}]] [163] => [164] => After repeated oral doses of 75 mg of clopidogrel (base), plasma concentrations of the parent compound, which has no platelet-inhibiting effect, are very low and, in general, are below the quantification limit (0.258 μg/L) beyond two hours after dosing.{{medical citation needed|date=November 2012}} [165] => [166] => Clopidogrel is a [[prodrug]], which is activated in two steps, first by the enzymes [[CYP2C19]], [[CYP1A2]] and [[CYP2B6]], then by CYP2C19, [[CYP2C9]], CYP2B6 and [[CYP3A]].{{cite journal|vauthors=Cattaneo M|title=Response variability to clopidogrel: is tailored treatment, based on laboratory testing, the right solution?|journal=Journal of Thrombosis and Haemostasis|date=March 2012|volume=10|issue=3|pages=327–36|doi=10.1111/j.1538-7836.2011.04602.x|pmid=22221409|s2cid=34477003| doi-access = free | title-link = doi }} Due to opening of the thiophene ring, the chemical structure of the active metabolite has three sites that are stereochemically relevant, making a total of eight possible isomers. These are: a stereocentre at C4 (attached to the —SH thiol group), a double bond at C3—C16, and the original stereocentre at C7. Only one of the eight structures is an active antiplatelet drug. This has the following configuration: ''Z'' configuration at the C3—C16 double bond, the original ''S'' configuration at C7, and, although the stereocentre at C4 cannot be directly determined, as the thiol group is too reactive, work with the active metabolite of the related drug prasugrel suggests the ''R''-configuration of the C4 group is critical for P2Y12 and platelet-inhibitory activity.{{medical citation needed|date=December 2011}} [167] => [168] => The active metabolite has an elimination half-life of about 0.5 to 1.0 h, and acts by forming a disulfide bridge with the platelet ADP receptor. Patients with a variant allele of CYP2C19 are 1.5 to 3.5 times more likely to die or have complications than patients with the high-functioning allele.{{cite journal | vauthors = Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS | title = Cytochrome p-450 polymorphisms and response to clopidogrel | journal = [[The New England Journal of Medicine]] | volume = 360 | issue = 4 | pages = 354–62 | date = January 2009 | pmid = 19106084 | doi = 10.1056/NEJMoa0809171 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, Steg PG, Ferrières J, Danchin N, ((Becquemont L, French Registry of Acute ST-Elevation Non-ST-Elevation Myocardial Infarction (FAST-MI) Investigators)) | title = Genetic Determinants of Response to Clopidogrel and Cardiovascular Events | journal = [[The New England Journal of Medicine]] | volume = 360 | issue = 4 | pages = 363–75 | date = January 2009 | pmid = 19106083 | doi = 10.1056/NEJMoa0808227 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Collet JP, Hulot JS, Pena A, Villard E, Esteve JB, Silvain J, Payot L, Brugier D, Cayla G, Beygui F, Bensimon G, Funck-Brentano C, Montalescot G | title = Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study | journal = [[The Lancet]] | volume = 373 | issue = 9660 | pages = 309–17 | date = January 2009 | pmid = 19108880 | doi = 10.1016/S0140-6736(08)61845-0 | s2cid = 22405890 }} [169] => [170] => Following an oral dose of 14C-labeled clopidogrel in humans, about 50% was excreted in the urine and 46% in the feces in the five days after dosing. [171] => [172] => * Effect of food: Administration of clopidogrel bisulfate with meals did not significantly modify the [[bioavailability]] of clopidogrel as assessed by the pharmacokinetics of the main circulating metabolite. [173] => * Absorption and distribution: Clopidogrel is rapidly absorbed after oral administration of repeated doses of 75-milligram clopidogrel (base), with peak plasma levels (about 3 mg/L) of the main circulating metabolite occurring around one hour after dosing. The pharmacokinetics of the main circulating metabolite are linear (plasma concentrations increased in proportion to dose) in the dose range of 50 to 150 mg of clopidogrel. Absorption is at least 50% based on urinary excretion of clopidogrel-related metabolites. [174] => Clopidogrel and the main circulating metabolite bind reversibly ''in vitro'' to human plasma proteins (98% and 94%, respectively). The binding is not saturable ''in vitro'' up to a concentration of 110 μg/mL. [175] => [176] => * Metabolism and elimination: ''In vitro'' and ''in vivo'', clopidogrel undergoes rapid hydrolysis into its [[carboxylic acid]] derivative. In plasma and urine, the glucuronide of the carboxylic acid derivative is also observed. [177] => [178] => In 2010, the US [[Food and Drug Administration]] (FDA) added a boxed warning, later updated, to Plavix, alerting that the drug can be less effective in people unable to metabolize the drug to convert it to its active form.{{Cite web |title=Safety announcement: Reduced effectiveness of Plavix in patients who are poor metabolizers |author= |publisher=U.S. Food and Drug Administration |date=3 August 2017 |url= https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-reduced-effectiveness-plavix-clopidogrel-patients-who-are-poor|url-status=live| archive-url = https://web.archive.org/web/20100315133622/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm204253.htm | archive-date = 15 March 2010}} [179] => [180] => === Pharmacogenetics === [181] => CYP2C19 is an important drug-metabolizing enzyme that catalyzes the biotransformation of many clinically useful drugs, including antidepressants, barbiturates, proton-pump inhibitors, and antimalarial and antitumor drugs. Clopidogrel is one of the drugs metabolized by this enzyme. [182] => [183] => The US [[Food and Drug Administration]] (FDA) added a [[boxed warning]] on clopidogrel in 2010 about CYP2C19-poor metabolizers. People with variants in cytochrome P-450 2C19 (CYP2C19) have lower levels of the active metabolite of clopidogrel, less inhibition of platelets, and a 3.58-times greater risk for major adverse cardiovascular events such as death, heart attack, and stroke; the risk was greatest in CYP2C19 poor metabolizers.{{cite web | title=FDA Drug Safety Communication: Reduced effectiveness of Plavix (clopidogrel) in patients who are poor metabolizers of the drug | website=U.S. [[Food and Drug Administration]] (FDA) | date=28 June 2019 | url=https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-reduced-effectiveness-plavix-clopidogrel-patients-who-are-poor | access-date=30 January 2022 | archive-date=18 June 2019 | archive-url=https://web.archive.org/web/20190618014631/https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-reduced-effectiveness-plavix-clopidogrel-patients-who-are-poor | url-status=live }} [184] => [185] => A published review showed that some mutations of ''CYP2C19'', ''CYP3A4'', ''CYP2C9'', ''CYP2B6'', and ''CYP1A2'' genes could affect the clinical efficacy and safety of clopidogrel treatment. For instance, patients carrying the mutations ''CYP2C19*2'', ''CYP2C19*3'', ''CYP2C9*2'', ''CYP2C9*3'', and ''CYP2B6*5'' alleles may not respond to clopidogrel due to poor platelet inhibition efficacy revealed among them.{{cite journal|doi=10.1080/17425255.2021.1925249|title=Polymorphisms of genes related to phase-I metabolic enzymes affecting the clinical efficacy and safety of clopidogrel treatment|date=June 2021|vauthors=Alkattan A, Alsalameen E|journal=Expert Opinion on Drug Metabolism & Toxicology|volume=17|issue=6|pages=685–95|pmid=33931001|s2cid=233470717}} [186] => [187] => === Mechanism of action === [188] => The active metabolite of clopidogrel specifically and irreversibly inhibits the [[P2Y12|P2Y12]] subtype of [[ADP receptor]], which is important in activation of platelets and eventual cross-linking by the protein [[fibrin]]. Platelet inhibition can be demonstrated two hours after a single dose of oral clopidogrel, but the onset of action is slow, so a loading dose of either 600 or 300 mg is administered when a rapid effect is needed.Clopidogrel {{Drugs.com|MTM|clopidogrel}}{{Full citation needed|date=January 2022}} [189] => [190] => == Society and culture == [191] => === Economics === [192] => [[File:Plavix 2007-04-19.jpg|thumb|right|A box of Plavix]] [193] => Plavix is marketed worldwide in nearly 110 countries, with sales of {{US$|6.6 [[billion]]}} in 2009.{{cite web |url=http://www1.imshealth.com/web/content/0,3148,64576068_63872702_70260998_77974518,00.html |title=New products and markets fuel growth in 2005 |publisher=[[IMS Health]] |access-date=2 March 2009 |url-status=dead |archive-url=https://web.archive.org/web/20080603032106/http://www.imshealth.com/web/content/0%2C3148%2C64576068_63872702_70260998_77974518%2C00.html |archive-date=3 June 2008 }} It was the second-top-selling drug in the world in 2007{{cite web |url=http://www.imshealth.com/deployedfiles/imshealth/Global/Content/StaticFile/Top_Line_Data/Top10GlobalProducts.pdf |title=Top Ten Global Products – 2007 |access-date=2 March 2009 |date=26 February 2008 |publisher=[[IMS Health]] |url-status=live |archive-url=https://web.archive.org/web/20110225085701/http://www.imshealth.com/deployedfiles/imshealth/Global/Content/StaticFile/Top_Line_Data/Top10GlobalProducts.pdf |archive-date=25 February 2011 }} and was still growing by over 20% in 2007. US sales were {{US$|3.8 billion}} in 2008.{{cite web |url=http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=PLAVIX |title=Details for Plavix |url-status=live |archive-url=https://web.archive.org/web/20140814162236/http://www.drugpatentwatch.com/ultimate/preview/tradename/index.php?query=PLAVIX |archive-date=14 August 2014}}{{verify source |date=May 2012}} [194] => [195] => Before the expiry of its patent, clopidogrel was the second best-selling drug in the world. In 2010, it grossed over {{US$|9 billion}} in global sales.{{cite journal |vauthors = Topol EJ, Schork NJ |title = Catapulting clopidogrel pharmacogenomics forward |journal = Nature Medicine |volume = 17 |issue = 1 |pages = 40–41 |date = January 2011 |pmid = 21217678 |doi = 10.1038/nm0111-40 |s2cid = 32083067}} [196] => [197] => In 2006, generic clopidogrel was briefly marketed by [[Apotex]], a [[Canada|Canadian]] generic [[pharmaceutical company]] before a court order halted further production until resolution of a patent infringement case brought by [[Bristol-Myers Squibb]].{{cite press release |url = http://www.prnewswire.com/news-releases/preliminary-injunction-against-apotex-upheld-on-appeal-56053592.html |title = Preliminary Injunction Against Apotex Upheld on Appeal |publisher = Bristol-Myers Squibb |date = 8 December 2006 |access-date = 14 March 2010 |url-status = live |archive-url=https://web.archive.org/web/20140414165229/http://www.prnewswire.com/news-releases/preliminary-injunction-against-apotex-upheld-on-appeal-56053592.html |archive-date = 14 April 2014}} The court ruled that Bristol-Myers Squibb's patent was valid and provided protection until November 2011.{{cite news |url=https://www.reuters.com/article/us-bristolmyers-plavix-patent-idUSN1931607820070619 |title=U.S. judge upholds Bristol, Sanofi patent on Plavix |publisher=Reuters |date=19 June 2007 |access-date=5 September 2007 |url-status=live |archive-url=https://web.archive.org/web/20110520015908/http://www.reuters.com/article/2007/06/19/us-bristolmyers-plavix-patent-idUSN1931607820070619 |archive-date=20 May 2011}} The FDA extended the patent protection of clopidogrel by six months, giving exclusivity that would expire in May 2012.{{cite news |url=http://ducknetweb.blogspot.com/2011/01/fda-gives-plavix-6-month-extension.html |title=FDA Gives Plavix a 6 Month Extension-Patent Now Expires on 17 May 2012 |date=26 January 2011 |access-date=12 January 2012 |url-status=live |archive-url=https://web.archive.org/web/20111012082734/http://ducknetweb.blogspot.com/2011/01/fda-gives-plavix-6-month-extension.html |archive-date=12 October 2011 }} The FDA approved generic versions of clopidogrel in May 2012.{{cite press release| title = FDA approves generic versions of blood thinner Plavix |date = 17 May 2012 |publisher = U.S. [[Food and Drug Administration]] (FDA) |url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm304489.htm |url-status = dead |archive-url=https://web.archive.org/web/20160311070234/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm304489.htm |archive-date = 11 March 2016}} [198] => [199] => === Names === [200] => Generic clopidogrel is marketed by many companies worldwide under many brand names. [201] => [202] => {{collapse top|List of brand names}} [203] => {{As of|March 2017}}, brands included Aclop, Actaclo, Agregex, Agrelan, Agrelax, Agreless, Agrelex, Agreplat, Anclog, Angiclod, Anplat, Antiagrex, Antiban, Antigrel, Antiplaq, Antiplar, Aplate, Apolets, Areplex, Artepid, Asogrel, Atelit, Atelit, Ateplax, Atervix, Atheros, Athorel, Atrombin, Attera, Bidogrel, Bigrel, Borgavix, Carder, Cardogrel, Carpigrel, Ceraenade, Ceruvin, Cidorix, Clatex, Clavix, Clentel, Clentel, Clidorel, Clodel, Clodelib, Clodian, Clodil, Cloflow, Clofre, Clogan, Clogin, Clognil, Clogrel, Clogrelhexal, Clolyse, Clont, Clood, Clopacin, Clopcare, Clopeno, Clopex Agrel, Clopez, Clopi, Clopid, Clopida, Clopidep, Clopidexcel, Clopidix, Clopidogrel, Clopidogrelum, Clopidomed, Clopidorex, Clopidosyn, Clopidoteg, Clopidowel, Clopidra, Clopidrax, Clopidrol, Clopigal, Clopigamma, Clopigrel, Clopilet, Clopimed, Clopimef, Clopimet, Clopinovo, Clopione, Clopiright, Clopirite, Clopirod, Clopisan, Clopistad, Clopistad, Clopitab, Clopithan, Clopitro, ClopiVale, Clopivas, Clopivaz, Clopivid, Clopivin, Clopix, Cloplat, Clopra, Cloprez, Cloprez, Clopval, Clorel, Cloriocard, Cloroden, Clotix, Clotiz, Clotrombix, Clova, Clovas, Clovax, Clovelen, Clovex, Clovexil, Clovix, Clovvix, Copalex, Copegrel, Copidrel, Copil, Cordiax, Cordix, Corplet, Cotol, CPG, Cugrel, Curovix, Dapixol, Darxa, Dasogrel-S, Dclot, Defrozyp, Degregan, Deplat, Deplatt, Diclop, Diloxol, Dilutix, Diporel, Doglix, Dogrel, Dogrel, Dopivix, Dorel, Dorell, Duopidogrel, DuoPlavin, Eago, Egitromb, Espelio, Eurogrel, Expansia, Farcet, Flucogrel, Fluxx, Freeclo, Globel, Glopenel, Grelet, Greligen, Grelix, Grepid, Grepid, Grindokline, Heart-Free, Hemaflow, Hyvix, Idiavix, Insigrel, Iscover, Iskimil, Kafidogran, Kaldera, Kardogrel, Karum, Kerberan, Keriten, Klepisal, Klogrel, Klopide, Klopidex, Klopidogrel, Klopik, Klopis, Kogrel, Krossiler, Larvin, Lodigrel, Lodovax, Lofradyk, Lopigalel, Lopirel, Lyvelsa, Maboclop, Medigrel, Miflexin, Mistro, Mogrel, Monel, Monogrel, Moytor, Myogrel, Nabratin, Nadenel, Nefazan, Niaclop, Nivenol, Noclog, Nofardom, Nogreg, Nogrel, Noklot, Norplat, Novigrel, Oddoral, Odrel, Olfovel, Opirel, Optigrel, Panagrel, Pedovex, Pegorel, Piax, Piclokare, Pidgrel, Pidogrel, Pidogul, Pidovix, Pigrel, Pingel, Placta, Pladel, Pladex, Pladogrel, Plagerine, Plagrel, Plagril, Plagrin, Plahasan, Plamed, Planor, PlaquEx, Plasiver, Plataca, Platarex, Platec, Platel, Platelex, Platexan, Platil, Platless, Platogrix, Platrel, Plavedamol, Plavicard, Plavictonal, Plavidosa, Plavigrel, Plavihex, Plavitor, Plavix, Plavocorin, Plavogrel, Plavos, Pleyar, Plogrel, Plvix, Pravidel, Pregrel, Provic, Psygrel, Q.O.L, Ravalgen, Replet, Respekt, Revlis, Ridlor, Roclas, Rozak, Sanvix, Sarix, Sarovex, Satoxi, Shinclop, Sigmagrel, Simclovix, Sintiplex, Stazex, Stroka, Stromix, Sudroc, Synetra, Talcom, Tansix, Tessyron, Thinrin, Throimper, Thrombifree, Thrombo, Timiflo, Tingreks, Torpido, Triosal, Trogran, Troken, Trombex, Trombix, Tuxedon, Unigrel, Unplaque, Vaclo, Vasocor, Vatoud, Venicil, Vidogrel, Vivelon, Vixam, Xydrel, Zakogrel, Zillt, Zopya, Zylagren, Zyllt, and Zystol.{{cite web |title=Clopidogrel International brand names |url=https://www.drugs.com/international/clopidogrel.html |publisher=Drugs.com |access-date=1 April 2017 |url-status=live |archive-url=https://web.archive.org/web/20170401144417/https://www.drugs.com/international/clopidogrel.html |archive-date=1 April 2017}} [204] => [205] => {{As of|2017}}, it was marketed as a [[combination drug]] with [[acetylsalicylic acid]] (aspirin) under the brand names Anclog Plus, Antiban-ASP, Asclop, Asogrel-A, Aspin-Plus, Cargrel-A, Clas, Clasprin, Clavixin Duo, Clodrel Forte, Clodrel Plus, Clofre AS, Clognil Plus, Clontas, Clopid-AS, Clopid-AS, Clopida A, Clopil-A, Clopirad-A, Clopirin, Clopitab-A, Clorel-A, Clouds, Combiplat, Coplavix, Coplavix, Cugrel-A, Dorel Plus, DuoCover, DuoCover, DuoPlavin, DuoPlavin, Ecosprin Plus, Grelet-A, Lopirel Plus, Myogrel-AP, Noclog Plus, Noklot Plus, Norplat-S, Odrel Plus, Pidogul A, Pladex-A, Plagerine-A, Plagrin Plus, Plavix Plus, Replet Plus, Stromix-A, and Thrombosprin. [206] => {{collapse bottom}} [207] => [208] => == Veterinary uses == [209] => Clopidogrel has been shown to be effective at decreasing platelet aggregation in cats, so its use in prevention of feline aortic thromboembolism has been advocated.{{cite journal | vauthors=Hogan DF, Andrews DA, Green HW, Talbott KK, Ward MP, Calloway BM | title = Antiplatelet effects and pharmacodynamics of clopidogrel in cats | journal = J Am Vet Med Assoc |year = 2004 | volume = 225 | issue = 9 | pages = 1406–1411 | doi = 10.2460/javma.2004.225.1406 | pmid=15552317| doi-access = free | title-link = doi }} [210] => [211] => == References == [212] => {{Reflist}} [213] => [214] => ==Further reading== [215] => * {{cite book | title=Medical Genetics Summaries | chapter=Clopidogrel Therapy and CYP2C19 Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK84114/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=3 | publisher=[[National Center for Biotechnology Information]] (NCBI) | year=2012 | pmid=28520346 | id=Bookshelf ID: NBK84114 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }} [216] => [217] => == External links == [218] => * [https://patents.google.com/patent/US4847265A/en US Patent US4847265A] for "Dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chlorophenyl)-acetate and the pharmaceutical compositions containing it" [219] => [220] => {{Antithrombotics}} [221] => {{Portal bar | Medicine}} [222] => {{Authority control}} [223] => [224] => [[Category:Adenosine diphosphate receptor inhibitors]] [225] => [[Category:Drugs developed by Bristol Myers Squibb]] [226] => [[Category:Carboxylate esters]] [227] => [[Category:Chlorobenzene derivatives]] [228] => [[Category:CYP2C8 inhibitors]] [229] => [[Category:Hepatotoxins]] [230] => [[Category:Methyl esters]] [231] => [[Category:Prodrugs]] [232] => [[Category:Sanofi]] [233] => [[Category:Thienopyridines]] [234] => [[Category:World Health Organization essential medicines]] [235] => [[Category:Wikipedia medicine articles ready to translate]] [] => )
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Clopidogrel

Clopidogrel is an antiplatelet medication used to prevent blood clots in people with various heart and blood vessel conditions. It is primarily prescribed to individuals with a history of heart attack, stroke, peripheral artery disease, or acute coronary syndrome.

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It is primarily prescribed to individuals with a history of heart attack, stroke, peripheral artery disease, or acute coronary syndrome. Clopidogrel works by inhibiting platelets from sticking together, reducing the formation of clots and preventing blockages in arteries. The drug is typically taken orally and its effects last for several days. Common side effects include bleeding, dizziness, and indigestion. Clopidogrel is considered safer in comparison to other similar medications due to a lower risk of excessive bleeding. The medication has been extensively studied and its effectiveness has been established through clinical trials.

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