Clopidogrel
From Wikipedia, the free encyclopedia
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Clopidogrel
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| Systematic (IUPAC) name | |
| (+)-(S)-methyl 2-(2-chlorophenyl)- 2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate |
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| Identifiers | |
| CAS number | |
| ATC code | B01 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C16H16ClNO2S |
| Mol. mass | 321.82 |
| Pharmacokinetic data | |
| Bioavailability | >50% |
| Metabolism | hepatic |
| Half life | 7–8 hours (inactive metabolite) |
| Excretion | 50% renal 46% biliary |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status | |
| Routes | oral |
Clopidogrel 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. 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. [1]In 2007, the production was halted to many retail pharmacies and will be changing back to Plavix. In 2005 it was the world's second highest selling pharmaceutical with sales of US$5.9 billion. [2]
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[edit] Pharmacology
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, but the onset of action is slow, so that a loading-dose of 300-600 mg is usually administered.
[edit] Clinical use
[edit] 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, as inhibition of the synthesis of prostaglandins by aspirin (acetylsalicylic acid) can exacerbate this condition. 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)
[edit] Dosage forms
Clopidogrel is marketed as clopidogrel bisulfate (clopidogrel hydrogen sulfate), most commonly under the trade name Plavix, as 75 mg oral tablets.
[edit] 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%)
[edit] References
- 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
[edit] External links
- Plavix : Information for the General Public
- Plavix, Aspirin and Stents : Patients' Forum : Angioplasty.Org
