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38-606: Clopidogrel , sold under the brand name Plavix among others, is an antiplatelet medication used to reduce the risk of heart disease and stroke in those at high risk. It is also used together with aspirin in heart attacks and following the placement of a coronary artery stent ( dual antiplatelet therapy ). It is taken by mouth . Its effect starts about two hours after intake and lasts for five days. Common side effects include headache, nausea , easy bruising, itching, and heartburn . More severe side effects include bleeding and thrombotic thrombocytopenic purpura . While there

76-479: A court order halted further production until resolution of a patent infringement case brought by Bristol-Myers Squibb . The court ruled that Bristol-Myers Squibb's patent was valid and provided protection until November 2011. The FDA extended the patent protection of clopidogrel by six months, giving exclusivity that would expire in May 2012. The FDA approved generic versions of clopidogrel in May 2012. Generic clopidogrel

114-453: A difference in mortality, major bleeds that require surgery, or ischaemic events. The same review found moderate certainty evidence that continuing or discontinuing therapy also did not have a big difference on the incidence of bleeds requiring a blood transfusion. Dentists should be aware of the risk of prolonged bleeding time in patients taking antiplatelet drugs when planning dental treatments that are likely to cause bleeding. Therefore, it

152-633: A low potential to interact with other pharmaceutical drugs. Combination with other drugs that affect blood clotting, such as aspirin , heparins and thrombolytics , showed no relevant interactions. Naproxen did increase the likelihood of occult gastrointestinal bleeding , as might be the case with other nonsteroidal anti-inflammatory drugs . 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

190-805: A related drug is recommended by the American Heart Association and the American College of Cardiology for people who: It is also used, along with acetylsalicylic acid (ASA, aspirin), for the prevention of thrombosis after placement of a coronary stent or as an alternative antiplatelet drug for people intolerant to aspirin. It is available as a fixed-dose combination with aspirin. 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. Consensus-based therapeutic guidelines also recommend

228-419: A stroke or heart attack. In this trial the following rates of bleeding were observed. 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. Rashes and itching were uncommon in studies (between 0.1 and 1% of people); serious hypersensitivity reactions are rare. Clopidogrel generally has

266-469: 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

304-508: Is a prodrug which is metabolized by the liver into its active form. The active form specifically and irreversibly inhibits the P2Y 12 subtype of ADP receptor , which is important in activation of platelets and eventual cross-linking by the protein fibrin . 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

342-414: Is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch , become warm, bumpy, chapped , dry, cracked or blistered , swell, and may be painful. The causes, and therefore treatments for rashes, vary widely. Diagnosis must take into account such things as the appearance of

380-417: Is important for dentists to know how to assess patient's bleeding risk and how to manage them. Identify the likelihood and risk of dental treatment causing bleeding complications. Antiplatelet drugs effect may be affected by patient's medications, current medical conditions, food and supplements taken. Antiplatelet drugs effect may be increased or decreased. An increase in antiplatelet effect would increase

418-565: Is irrelevant for practical purposes. In November 2009, the US Food and Drug Administration (FDA) announced that clopidogrel should be used with caution in people using the proton-pump inhibitors omeprazole or esomeprazole , but pantoprazole appears to be safe. The newer antiplatelet agent prasugrel has minimal interaction with (es)omeprazole, hence might be a better antiplatelet agent (if no other contraindications are present) in people who are on these proton-pump inhibitors. Clopidogrel

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456-3164: Is marketed by many companies worldwide under many brand names. 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. As of 2017, it

494-520: Is no evidence of harm from use during pregnancy , such use has not been well studied. Clopidogrel is in the thienopyridine -class of antiplatelets. It works by irreversibly inhibiting a receptor called P2Y 12 on platelets . Clopidogrel was patented in 1982, and approved for medical use in 1997. It is on the World Health Organization's List of Essential Medicines . In 2022, it was the 47th most commonly prescribed medication in

532-409: Is not used in low-risk patients because it significantly increases the risks of major bleeding . Classes of antiplatelet drugs include: Prevention and treatment of arterial thrombosis is essential in patients with certain medical conditions whereby the risk of thrombosis or thromboembolism may result in disastrous consequences such as heart attack, pulmonary embolism or stroke. Patients who require

570-429: Is one of the drugs metabolized by this enzyme. 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;

608-487: Is real. Serious adverse drug reactions associated with clopidogrel therapy include: 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: The CAPRIE trial compared clopidogrel monotherapy to aspirin monotherapy for 1.6 years in people who had recently experienced

646-422: Is required for the conversion of clopidogrel to its active form. The European Medicines Agency has issued a public statement on a possible interaction between clopidogrel and proton-pump inhibitors. 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

684-435: Is used as a single medication in cases of uncomplicated stable angina , and in some cases of unstable angina . If a patient does not tolerate aspirin , ADP/P2Y inhibitors may be used as single-drug therapy instead. More severe and complicated cases are treated with dual antiplatelet therapy, or in some cases triple therapy that includes direct oral anticoagulants . Clinicians must make a choice that balances patient risk with

722-459: The P2Y 12 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. Plavix is marketed worldwide in nearly 110 countries, with sales of US$ 6.6 billion in 2009. It

760-447: 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. 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

798-463: The United States, with more than 13   million prescriptions. It is available as a generic medication . 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 . Treatment with clopidogrel or

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836-487: The ability of blood clots to form by interfering with the platelet activation process in primary hemostasis . Antiplatelet drugs can reversibly or irreversibly inhibit the process involved in platelet activation resulting in decreased tendency of platelets to adhere to one another and to damaged blood vessels' endothelium. Antiplatelet medications are one of the primary recommendations for treatment of both stable and unstable ischemic heart disease . Most commonly, aspirin

874-426: The examination include: A patch test may be ordered, for diagnostic purposes. Treatment differs according to which rash a patient has been diagnosed with. Common rashes can be easily remedied using steroid topical creams (such as hydrocortisone ) or non-steroidal treatments. Many of the medications are available over the counter in the United States. The problem with steroid topical creams i.e. hydrocortisone;

912-433: The head, and spreads downwards. Common causes of rashes include: Uncommon causes: The causes of a rash are numerous, which may make the evaluation of a rash extremely difficult. An accurate evaluation by a provider may only be made in the context of a thorough history, i.e. medications the patient is taking, the patient's occupation, where the patient has been and complete physical examination. Points typically noted in

950-400: The high-functioning allele. Following an oral dose of C-labeled clopidogrel in humans, about 50% was excreted in the urine and 46% in the feces in the five days after dosing. 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. In 2010,

988-625: The increased risks of bleeding associated with combination therapy. Often a combination of aspirin plus an ADP/P2Y inhibitor (such as clopidogrel , prasugrel , ticagrelor , or another) is used to obtain greater effectiveness than with either agent alone. This is known as "dual antiplatelet therapy" (or DAPT ). DAPT is used in patients who have, or are at high risk of developing, unstable angina, NSTEMI myocardial infarctions, and other high-risk thrombotic conditions. Dual antiplatelet therapy has been found to significantly reduce rates of heart attacks, strokes , and overall cardiovascular death, but

1026-403: The quantification limit (0.258 μg/L) beyond two hours after dosing. 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 . The thiophene ring is converted to a thiolactone , which undergoes ring-opening. The active metabolite has three sites that are stereochemically relevant, making

1064-440: The rash, other symptoms, what the patient may have been exposed to, occupation, and occurrence in family members. The diagnosis may confirm any number of conditions. The presence of a rash may aid diagnosis; associated signs and symptoms are diagnostic of certain diseases. For example, the rash in measles is an erythematous , morbilliform , maculopapular rash that begins a few days after the fever starts. It classically starts at

1102-690: The risk of bleeding and could cause prolonged or excessive bleeding. A decrease in antiplatelet effect would reduce the risk of bleeding, but increase the thromboembolic risk. Drug toxicity may increase when multiple antiplatelet drugs are used. Gastrointestinal bleeding is a common adverse event seen in many patients. Medications that may increase antiplatelet drug effect: Medications that may decrease antiplatelet drug effect: Use of NSAIDs as part of dental management of patients with vascular disease should be discouraged as NSAIDs have antiplatelet effect. Instead, simple analgesics such as paracetamol or co-codamol should be of first choice. If NSAIDs are required,

1140-549: The risk of bleeding increases with duration of dental treatment. Medical conditions that may increase antiplatelet drugs' effect include: Chronic kidney failure , liver disease , haematological malignancy, recent or current chemotherapy , advanced heart failure, mild forms of inherited bleeding disorders (e.g. haemophilia , Von Willebrand's disease ) and idiopathic thrombocytopenic purpura . Food and supplements that may increase antiplatelet drugs' effect: St. John's wort, ginkgo biloba, garlic. Rashes A rash

1178-579: The risk was greatest in CYP2C19 poor metabolizers. 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. The active metabolite of clopidogrel specifically and irreversibly inhibits

Clopidogrel - Misplaced Pages Continue

1216-414: The risk-benefit ratio in the perioperative period, one must consider the risk of stopping the medication and a clot forming versus the risk of bleeding during or after the surgery if medication is continued. A 2018 Cochrane Review that included five randomized controlled trials found low-certainty evidence to suggest that continuing or discontinuing antiplatelet therapy for a non-cardiac surgery does not make

1254-524: 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 P2Y 12 and platelet-inhibitory activity. 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

1292-410: The use of antiplatelet drugs and thrombolytic therapy . Antiplatelet drugs alter the platelet activation at the site of vascular damage crucial to the development of arterial thrombosis. Antiplatelet therapy may increase the risk of a bleed during surgery, however, stopping therapy may increase the risk of other thrombotic problems including myocardial infarction. When considering these medications and

1330-407: The use of antiplatelet drugs are: stroke with or without atrial fibrillation, any heart surgery (especially prosthetic replacement heart valve), Coronary Heart Disease such as stable angina, unstable angina and heart attack, patients with coronary stent, Peripheral Vascular Disease/Peripheral Arterial Disease and apical/ventricular/mural thrombus. Treatment of established arterial thrombosis includes

1368-609: 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. 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

1406-1167: 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. 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. Antiplatelet drug Antiplatelet drugs are widely used in primary and secondary prevention of thrombotic disease, especially myocardial infarction and ischemic stroke . Antiplatelet therapy with one or more of these drugs decreases

1444-404: Was the second-top-selling drug in the world in 2007 and was still growing by over 20% in 2007. US sales were US$ 3.8 billion in 2008. 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. In 2006, generic clopidogrel was briefly marketed by Apotex , a Canadian generic pharmaceutical company before

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