Clopidogrel
Encyclopedia
Clopidogrel is an oral, thienopyridine
class antiplatelet agent
used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease
. It is marketed by Bristol-Myers Squibb
and Sanofi-Aventis
under the trade name
Plavix. The drug works by irreversibly inhibiting a receptor called P2Y12
, an adenosine diphosphate
ADP chemoreceptor. Adverse effects include hemorrhage, severe neutropenia
, and thrombotic thrombocytopenic purpura
(TTP).
, the action of which may be related to an adenosine diphosphate (ADP) receptor on platelet
cell membranes. The drug specifically and irreversibly inhibits the P2Y12
subtype of ADP receptor, which is important in aggregation of platelets and cross-linking by the protein fibrin
. The blockade of this receptor inhibits platelet aggregation by blocking activation of the glycoprotein IIb/IIIa
pathway. The IIb/IIIa complex functions as a receptor mainly for fibrinogen
and vitronectin
but also for fibronectin and von Willebrand factor
. Activation of this receptor complex is the "final common pathway" for platelet aggregation and is important in the cross-linking of platelets by fibrin.
Platelet inhibition can be demonstrated two hours after a single dose of oral clopidogrel, but the onset of action is slow, so that a loading-dose of 300–600 mg is usually administered.
a stereocentre at C4 (attached to the —SH thiol group), a stereobond at C3—C16 double bound and
the original stereocentre at C7.
Only one of the eight structures is an active antiplatelet drug. This has the following configuration; a (Z) configuration at C3—C16 double bound, the original (S) configuration stereocentre at C7 and although the stereocentre at C4 can't be directly determined, as the thiol group is too reactive, work with the active metabolite of the related drug Prasugrel suggests that the (R)-configuration of the C4 group is critical for P2Y12 and platelet-inhibitory activities.
It is also used, along with aspirin, for the prevention of thrombosis
after placement of intracoronary stent
or as an alternative antiplatelet drug for patients who are intolerant to aspirin.
International guidelines granted the highest grade of recommendation for NSTE-ACS, PCI and stent, for clopidogrel in addition to aspirin. Consensus-based therapeutic guidelines recommend also the use of clopidogrel, instead of aspirin
, in patients requiring antiplatelet therapy but with a history of gastric ulceration, as inhibition of the synthesis of prostaglandins by aspirin (acetylsalicylic acid) can exacerbate this condition. A study has shown that in patients with healed aspirin-induced ulcers, however, patients receiving aspirin plus the proton pump inhibitor
esomeprazole
had a lower incidence of recurrent ulcer bleeding than patients receiving clopidogrel. However, a more recent study suggested that prophylaxis with proton pump inhibitor
s 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. 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 there really is an interaction between clopidogrel and proton pump inhibitors.
Clopidogrel is a pro-drug activated in the liver by cytochrome P450 enzymes, including CYP2C19
. The active metabolite has an elimination half-life of about eight hours 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.
Following an oral dose of 14C-labeled clopidogrel in humans, approximately 50% was excreted in the urine and approximately 46% in the feces in the five days after dosing.
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.
Absorption and Distribution: Clopidogrel is rapidly absorbed after oral administration of repeated doses of 75 mg clopidogrel (base), with peak plasma levels (appx. 3 mg/L) of the main circulating metabolite occurring approximately 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.
Clopidogrel and the main circulating metabolite bind reversibly in vitro to human plasma proteins (98% and 94%, respectively). The binding is nonsaturable in vitro up to a concentration of 110 μg/mL.
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.
In March 2010, the U.S. Food and Drug Administration (FDA) added a boxed warning to Plavix alerting that the drug can be less effective in people who cannot metabolize the drug to convert it to its active form.
Several recent landmark studies have proven the importance of 2C19 genotyping in treatment using clopidogrel or Plavix. In March 2010, the FDA put a black box warning on Plavix to make patients and healthcare providers aware that CYP2C19 poor metabolizers, representing up to 14% of patients, are at high risk of treatment failure and that testing is available. Researchers have found that patients 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.
s associated with clopidogrel therapy include:
s (except possibly pantoprazole
), phenytoin
(Dilantin); tamoxifen
(Nolvadex); tolbutamide
(Orinase); torsemide (Demadex); fluvastatin
(Lescol); a blood thinner such as warfarin
(Coumadin), heparin
, ardeparin
(Normiflo), dalteparin
(Fragmin), danaparoid
(Orgaran), enoxaparin
(Lovenox), or tinzaparin
(Innohep); (Activase), anistreplase
(Eminase), dipyridamole
(Persantine), streptokinase
(Kabikinase, Streptase), ticlopidine
(Ticlid), and urokinase
(Abbokinase).
In November 2009, the FDA announced that clopidogrel should not be taken with proton pump inhibitors such as omeprazole
and esomeprazole
.
Plavix is marketed worldwide in nearly 110 countries, with sales of US$6.6 billion in 2009. It had been the 2nd top selling drug in the world for a few years as of 2007 and was still growing by over 20% in 2007. U.S. sales were US$3.8 billion in 2008.
In 2006, generic clopidogrel was briefly marketed by Apotex
, a Canadian
generic pharmaceutical company
before 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.
Generic clopidogrel is also produced by several pharmaceutical companies in India. Clopidogrel is marketed by Sun Pharmaceuticals
under the trade name
Clopilet, by Ranbaxy Laboratories under the trade name Ceruvin, and under the name "Clavix" by Intas Pharmaceuticals and under the name "Deplatt" by Torrent Pharmaceuticals. In India, it is sold as Clopigrel, Clopitab, Clopijoy, and Clasprin (mixed with aspirin).
Thienopyridine
Thienopyridines are a class of ADP receptor/P2Y12 inhibitors used for their anti-platelet activity.-Examples:These drugs include:Prasugrel ,Ticlopidine ,Clopidogrel ....
class antiplatelet agent
Antiplatelet drug
An antiplatelet drug is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation...
used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease
Cerebrovascular disease
Cerebrovascular disease is a group of brain dysfunctions related to disease of the blood vessels supplying the brain. Hypertension is the most important cause; it damages the blood vessel lining, endothelium, exposing the underlying collagen where platelets aggregate to initiate a repairing process...
. It is marketed by Bristol-Myers Squibb
Bristol-Myers Squibb
Bristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...
and Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
under the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
Plavix. The drug works by irreversibly inhibiting a receptor called P2Y12
P2Y12
In the field of molecular biology, the P2Y12 protein is found mainly but not only on the surface of blood platelet cells and is an important regulator in blood clotting....
, an adenosine diphosphate
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
ADP chemoreceptor. Adverse effects include hemorrhage, severe neutropenia
Neutropenia
Neutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
, and thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body...
(TTP).
Pharmacology
Clopidogrel is a prodrugProdrug
A prodrug is a pharmacological substance administered in an inactive form. Once administered, the prodrug is metabolised in vivo into an active metabolite, a process termed bioactivation. The rationale behind the use of a prodrug is generally for absorption, distribution, metabolism, and...
, the action of which may be related to an adenosine diphosphate (ADP) receptor on platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
cell membranes. The drug specifically and irreversibly inhibits the P2Y12
P2Y12
In the field of molecular biology, the P2Y12 protein is found mainly but not only on the surface of blood platelet cells and is an important regulator in blood clotting....
subtype of ADP receptor, which is important in aggregation of platelets and cross-linking by the protein fibrin
Fibrin
Fibrin is a fibrous, non-globular protein involved in the clotting of blood. It is a fibrillar protein that is polymerised to form a "mesh" that forms a hemostatic plug or clot over a wound site....
. The blockade of this receptor inhibits platelet aggregation by blocking activation of the glycoprotein IIb/IIIa
Glycoprotein IIb/IIIa
In medicine, glycoprotein IIb/IIIa is an integrin complex found on platelets. It is a receptor for fibrinogen and aids in platelet activation. The complex is formed via calcium-dependent association of gpIIb and gpIIIa, a required step in normal platelet aggregation and endothelial adherence...
pathway. The IIb/IIIa complex functions as a receptor mainly for fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
and vitronectin
Vitronectin
Vitronectin also known as VTN is a protein that in humans is encoded by the VTN gene.The protein encoded by this gene is a member of the pexin family...
but also for fibronectin and von Willebrand factor
Von Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...
. Activation of this receptor complex is the "final common pathway" for platelet aggregation and is important in the cross-linking of platelets by fibrin.
Platelet inhibition can be demonstrated two hours after a single dose of oral clopidogrel, but the onset of action is slow, so that a loading-dose of 300–600 mg is usually administered.
Chemistry
Due to opening of the thiophene ring, the metabolite chemical structure now has three sites of chirality, making a total of eight possible isomers. These are;a stereocentre at C4 (attached to the —SH thiol group), a stereobond at C3—C16 double bound and
the original stereocentre at C7.
Only one of the eight structures is an active antiplatelet drug. This has the following configuration; a (Z) configuration at C3—C16 double bound, the original (S) configuration stereocentre at C7 and although the stereocentre at C4 can't be directly determined, as the thiol group is too reactive, work with the active metabolite of the related drug Prasugrel suggests that the (R)-configuration of the C4 group is critical for P2Y12 and platelet-inhibitory activities.
Indications
Clopidogrel is indicated for:- Prevention of vascular ischemic events in patients with symptomatic atherosclerosisAtherosclerosisAtherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
- Acute coronary syndrome without ST-segment elevation (NSTEMIMyocardial infarctionMyocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
), - ST elevation MI (STEMI)
It is also used, along with aspirin, for the prevention of thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
after placement of intracoronary stent
Stent
In the technical vocabulary of medicine, a stent is an artificial 'tube' inserted into a natural passage/conduit in the body to prevent, or counteract, a disease-induced, localized flow constriction. The term may also refer to a tube used to temporarily hold such a natural conduit open to allow...
or as an alternative antiplatelet drug for patients who are intolerant to aspirin.
International guidelines granted the highest grade of recommendation for NSTE-ACS, PCI and stent, for clopidogrel in addition to aspirin. Consensus-based therapeutic guidelines recommend also the use of clopidogrel, instead of aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
, in patients requiring antiplatelet therapy but with a history of gastric ulceration, as inhibition of the synthesis of prostaglandins by aspirin (acetylsalicylic acid) can exacerbate this condition. A study has shown that in patients with healed aspirin-induced ulcers, however, patients receiving aspirin plus the proton pump inhibitor
Proton pump inhibitor
Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...
esomeprazole
Esomeprazole
Esomeprazole is a proton pump inhibitor developed and marketed by AstraZeneca which is used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease and Zollinger-Ellison syndrome...
had a lower incidence of recurrent ulcer bleeding than patients receiving clopidogrel. However, a more recent study suggested that prophylaxis with proton pump inhibitor
Proton pump inhibitor
Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...
s along with clopidogrel following acute coronary syndrome
Acute coronary syndrome
Acute coronary syndrome is usually one of three diseases involving the coronary arteries: ST elevation myocardial infarction , non ST elevation myocardial infarction , or unstable angina ....
may increase adverse cardiac outcomes, possibly due to inhibition of CYP2C19
CYP2C19
Cytochrome P450 2C19 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. It is involved in the metabolism of several...
, which is required for the conversion of clopidogrel to its active form. The European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
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 there really is an interaction between clopidogrel and proton pump inhibitors.
Dosage forms
Clopidogrel is marketed as clopidogrel bisulfate (clopidogrel hydrogen sulfate), most commonly under the trade names Plavix, as 75 mg oral tablets.Pharmacokinetics and metabolism
After repeated 75-mg oral doses of clopidogrel (base), plasma concentrations of the parent compound, which has no platelet inhibiting effect, are very low and are generally below the quantification limit (0.000258 mg/L) beyond two hours after dosing.Clopidogrel is a pro-drug activated in the liver by cytochrome P450 enzymes, including CYP2C19
CYP2C19
Cytochrome P450 2C19 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. It is involved in the metabolism of several...
. The active metabolite has an elimination half-life of about eight hours 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.
Following an oral dose of 14C-labeled clopidogrel in humans, approximately 50% was excreted in the urine and approximately 46% in the feces in the five days after dosing.
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.
Absorption and Distribution: Clopidogrel is rapidly absorbed after oral administration of repeated doses of 75 mg clopidogrel (base), with peak plasma levels (appx. 3 mg/L) of the main circulating metabolite occurring approximately 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.
Clopidogrel and the main circulating metabolite bind reversibly in vitro to human plasma proteins (98% and 94%, respectively). The binding is nonsaturable in vitro up to a concentration of 110 μg/mL.
Metabolism and Elimination: In vitro and in vivo, clopidogrel undergoes rapid hydrolysis into its carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
derivative. In plasma and urine, the glucuronide of the carboxylic acid derivative is also observed.
In March 2010, the U.S. Food and Drug Administration (FDA) added a boxed warning to Plavix alerting that the drug can be less effective in people who cannot metabolize the drug to convert it to its active form.
Pharmacogenetics
CYP2C19 is an important drug-metabolizing enzyme that catalyzes the biotransformation of many clinically useful drugs including antidepressants, barbiturates, proton pump inhibitors, antimalarial and antitumor drugs. Clopidogrel is one of the drugs metabolized by this enzyme.Several recent landmark studies have proven the importance of 2C19 genotyping in treatment using clopidogrel or Plavix. In March 2010, the FDA put a black box warning on Plavix to make patients and healthcare providers aware that CYP2C19 poor metabolizers, representing up to 14% of patients, are at high risk of treatment failure and that testing is available. Researchers have found that patients 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.
Adverse effects
Serious adverse drug reactionAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s associated with clopidogrel therapy include:
- Severe neutropeniaNeutropeniaNeutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
(low white blood cells) (Incidence: 1/2,000) - Thrombotic thrombocytopenic purpuraThrombotic thrombocytopenic purpuraThrombotic thrombocytopenic purpura is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body...
(TTP) (Incidence: 4/1,000,000 patients treated) - Hemorrhage - The annual incidence of hemorrhage may be increased by the co-administration of aspirinAspirinAspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
.- Gastrointestinal Hemorrhage (Incidence: 2.0% annually)
- Cerebral Hemorrhage (Incidence: 0.1 to 0.4% annually)
- Use of non-steroidal anti-inflammatory drugNon-steroidal anti-inflammatory drugNonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
s is discouraged in those taking clopidogrel due to increased risk of digestive tract hemorrhage
- Certain serious side effects include: skin irritations, respiratory difficulties, bloody stools and vomit, bloating of facial features, limbs and joints, exhaustion etc.
Interactions
Clopidogrel interacts with the following drugs: proton pump inhibitorProton pump inhibitor
Proton-pump inhibitors are a group of drugs whose main action is a pronounced and long-lasting reduction of gastric acid production. They are the most potent inhibitors of acid secretion available today. The group followed and has largely superseded another group of pharmaceuticals with similar...
s (except possibly pantoprazole
Pantoprazole
Pantoprazole is a proton pump inhibitor drug that inhibits gastric acid secretion.-Use:...
), phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
(Dilantin); tamoxifen
Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
(Nolvadex); tolbutamide
Tolbutamide
Tolbutamide is a first generation potassium channel blocker, sulfonylurea oral hypoglycemic drug sold under the brand name Orinase. This drug may be used in the management of type II diabetes if diet alone is not effective. Tolbutamide stimulates the secretion of insulin by the pancreas...
(Orinase); torsemide (Demadex); fluvastatin
Fluvastatin
Fluvastatin is a member of the drug class of statins, used to treat hypercholesterolemia and to prevent cardiovascular disease....
(Lescol); a blood thinner such as warfarin
Warfarin
Warfarin is an anticoagulant. It is most likely to be the drug popularly referred to as a "blood thinner," yet this is a misnomer, since it does not affect the thickness or viscosity of blood...
(Coumadin), heparin
Heparin
Heparin , also known as unfractionated heparin, a highly sulfated glycosaminoglycan, is widely used as an injectable anticoagulant, and has the highest negative charge density of any known biological molecule...
, ardeparin
Ardeparin
Ardeparin is an anticoagulant. It was used for the prevention of deep vein thrombosis, but was withdrawn form the US market in 2000....
(Normiflo), dalteparin
Dalteparin
Dalteparin is a low molecular weight heparin. It is marketed as Fragmin by Pfizer Inc. Like other low molecular weight heparins, dalteparin is used for prophylaxis or treatment of deep vein thrombosis and pulmonary embolism....
(Fragmin), danaparoid
Danaparoid
Danaparoid sodium is an anticoagulant that works by inhibiting activated factor X .Danaparoid is considered a "low molecular weight heparin" by some sources, but is chemically distinct from heparin and thus has little cross-reactivity in heparin-intolerant patients.It consists of a mixture of...
(Orgaran), enoxaparin
Enoxaparin
Enoxaparin is a low molecular weight heparin marketed under the trade names Lovenox and Clexane, among others. It is an anticoagulant used to prevent and treat deep vein thrombosis or pulmonary embolism, and is given as a subcutaneous injection...
(Lovenox), or tinzaparin
Tinzaparin
Tinzaparin is an antithrombotic drug in the heparin group. It is a low molecular weight heparin marketed as Innohep worldwide. It has been approved by the U.S. Food and Drug Administration for once daily treatment and prophylaxis of deep vein thrombosis and pulmonary embolism...
(Innohep); (Activase), anistreplase
Anistreplase
Anistreplase is a thrombolytic drug.Anistreplase has been developed by Beecham as Eminase. It is also known as anisoylated plasminogen streptokinase activator complex -Mechanism:...
(Eminase), dipyridamole
Dipyridamole
Dipyridamole is a drug that inhibits thrombus formation when given chronically and causes vasodilation when given at high doses over a short time.-Mechanism and effects:...
(Persantine), streptokinase
Streptokinase
Streptokinase , a protein secreted by several species of streptococci can bind and activate human plasminogen. SK is used as an effective and inexpensive thrombolysis medication in some cases of myocardial infarction and pulmonary embolism...
(Kabikinase, Streptase), ticlopidine
Ticlopidine
Ticlopidine is an antiplatelet drug in the thienopyridine family. Like clopidogrel, it is an adenosine diphosphate receptor inhibitor. It is used in patients in whom aspirin is not tolerated, or in whom dual antiplatelet therapy is desirable...
(Ticlid), and urokinase
Urokinase
Urokinase , also called urokinase-type plasminogen activator , is a serine protease . Urokinase was originally isolated from human urine, but is present in several physiological locations, such as blood stream and the extracellular matrix...
(Abbokinase).
In November 2009, the FDA announced that clopidogrel should not be taken with proton pump inhibitors such as omeprazole
Omeprazole
Omeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease , laryngopharyngeal reflux and Zollinger–Ellison syndrome...
and esomeprazole
Esomeprazole
Esomeprazole is a proton pump inhibitor developed and marketed by AstraZeneca which is used in the treatment of dyspepsia, peptic ulcer disease , gastroesophageal reflux disease and Zollinger-Ellison syndrome...
.
Marketing and litigation
In 2006, generic clopidogrel was briefly marketed by Apotex
Apotex
Apotex is a Canadian pharmaceutical corporation. Founded in 1974, the company is the largest producer of generic drugs in Canada, with sales exceeding one billion dollars a year...
, a Canadian
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
generic pharmaceutical company
Pharmaceutical company
The pharmaceutical industry develops, produces, and markets drugs licensed for use as medications. Pharmaceutical companies are allowed to deal in generic and/or brand medications and medical devices...
before a court order halted further production until resolution of a patent infringement case brought by Bristol-Myers Squibb
Bristol-Myers Squibb
Bristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...
. The court ruled that Bristol-Myers Squibb's patent was valid and provided protection until November 2011.
Generic clopidogrel is also produced by several pharmaceutical companies in India. Clopidogrel is marketed by Sun Pharmaceuticals
Sun Pharmaceuticals
Sun Pharmaceutical is an international pharmaceutical company based in Mumbai, India. It should not be confused with Sun Pharmaceuticals Corp, which is a manufacturer of sun care products, owned by the Playtex branch of Energizer Holdings.Sun Pharmaceutical, often known just as Sun Pharma, makes...
under the trade name
Trade name
A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....
Clopilet, by Ranbaxy Laboratories under the trade name Ceruvin, and under the name "Clavix" by Intas Pharmaceuticals and under the name "Deplatt" by Torrent Pharmaceuticals. In India, it is sold as Clopigrel, Clopitab, Clopijoy, and Clasprin (mixed with aspirin).
External links
- Plavix official website Bristol-Myers SquibbBristol-Myers SquibbBristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...
/Sanofi-AventisSanofi-AventisSanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the... - Plavix prescribing information Bristol-Myers SquibbBristol-Myers SquibbBristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...
/Sanofi-AventisSanofi-AventisSanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the... - Plavix, Aspirin and Stents : Patients' Forum : Angioplasty.Org
- Drug promises end to migraine misery
- U.S. National Library of Medicine: Drug Information Portal - Clopidogrel