Clopidogrel (IPA: ) is a potent oral antiplatelet agent often used in the treatment of coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix.

Pharmacology

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The mechanism of action of clopidogrel is irreversible blockade of the adenosine diphosphate (ADP) receptor on platelet cell membranes. This receptor is named P2Y12 and is important in platelet aggregation, the cross-linking of platelets by fibrin. The blockade of this receptor inhibits platelet aggregation by blocking activation of the glycoprotein IIb/IIIa pathway.

Platelet inhibition can be demonstrated two hours after a single dose of oral clopidogrel.

Clinical use

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Indications

Clopidogrel is indicated for (Rossi, 2006):

• Prevention of vascular ischaemic events in patients with symptomatic atherosclerosis
• Acute coronary syndrome without ST-segment elevation (NSTEMI), along with aspirin

It is also used, along with aspirin, for the prevention of thromboembolism after placement of intracoronary stent. (Rossi, 2006)

Most consensus-based therapeutic guidelines recommend the use of clopidogrel, over aspirin, in patients requiring antiplatelet therapy but with a history of gastric ulceration, due to the lower incidence of gastric ulceration associated with the use of clopidogrel vs aspirin. A recent 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. (Chan et al., 2005)

Dosage forms

Clopidogrel is marketed as clopidogrel bisulfate (clopidogrel hydrogen sulfate), most commonly under the trade name Plavix, as 75 mg tablets.

Adverse effects

Serious adverse drug reactions associated with clopidogrel therapy include:

• Severe neutropenia (Incidence: 5/10,000)
• Thrombotic thrombocytopenic purpura (TTP) (Incidence: 4/1,000,000 patients treated)
• Hemorrhage - The incidence of hemorrhage may be increased by the co-administration of aspirin.
  • Gastrointestinal Hemorrhage (Incidence: 2.0%)
  • Cerebral Hemorrhage (Incidence: 0.1 to 0.4%)

References

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• Chan FKL, Ching JYL, Hung LCT, Wong VWS, Leung VKS, Kung NNS, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. New Engl J Med 2005;352(3):238-244.
• Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3

External links

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• Plavix : Information for the General Public
• Plavix : Primary Care Physician
• Plavix : Cardiology
• Plavix : Neurology

Antiplatelet drugs | ADP receptor inhibitors | Sanofi-Aventis

Clopidogrel | Clopidogrel | Clopidogrel