Clopidogrel

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Clopidogrel is an antiplatelet agent used to inhibit blood clots in a variety of conditions. Platelets are very small structures in the blood, which clump together during blood clotting. By preventing this clumping, Clopidogrel reduces the chances of blood clots forming in hardened blood vessels (arteries), a process known as atherothrombosis, which can lead to atherothrombotic events (such as stroke, heart attack, or death).

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[edit] STRUCTURE

Clopidogrel.jpg

[edit] MECHANISM OF ACTION

Clopidogrel, is an inhibitor of platelet aggregation, structurally and pharmacologically similar to ticlopidine. Clopidogrel helps to prevent blood clots from forming. When the blood clots, this is due to special cells in the blood, the platelets, sticking together (aggregating).

The active metabolite of clopidogrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor P2Y12, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation.

This action is irreversible. Consequently, platelets exposed to clopidogrel’s active metabolite are affected for the remainder of their lifespan (about 7 to 10 days).

[edit] INDICATIONS

  • To reduce atherosclerotic events such as myocardial infarction, stroke, and vascular death in patients who have had a recent stroke, recent MI, or have established peripheral vascular disease. Clopidogrel is recommended as an alternative to aspirin in patients with aspirin hypersensitivity.
  • in combination with aspirin for Acute myocardial infarction without ST segment elevation (NSTEMI).
  • in combination with aspirin for Acute myocardial infarction with ST segment elevation (STEMI).

[edit] DOSAGE

  • Recent MI, recent stroke, or established peripheral arterial disease: 75 mg once daily
  • Acute myocardial infarction without ST segment elevation (NSTEMI): 300 mg loading dose followed by 75 mg once daily, in combination with aspirin (75-325 mg once daily). NICE recommends aspirin 75 mg daily in combination with clopidogrel 75 mg daily for 12 months after the most recent acute episode.
  • Acute myocardial infarction with ST segment elevation (STEMI): 75 mg once daily, in combination with aspirin (75-325 mg once daily), with or without a loading dose and with or without thrombolytics. Patients should be treated as early as possible or at the time of primary percutaneous coronary intervention (PCI). this combination should be continued for at least four weeks.

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Clopidogrel or any of the other ingredients.
  • Active pathological bleeding such as peptic ulcer or intracranial hemorrhage

[edit] WARNINGS AND PRECAUTIONS

  • CYP2C19 : Clopidogrel is a prodrug, its effectiveness depends on activation to an active metabolite, principally by CYP2C19. Genetic variations in CYP2C19 affects the metabolic transformation of clopidogrel into its active form. Tests are available to identify a patient’s CYP2C19 genotype and can be used as an aid in determining therapeutic strategy and an alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers should be considered.
  • Bleeding: Clopidogrel increases the risk of bleeding. Discontinue 5 days prior to elective surgery.
  • Discontinuations: Patients who require discontinuation of Clopidogrel are at increased risk for cardiac events. Premature discontinuation of treatment should be avoided.
  • Recent transient ischemic attack or stroke: Combination use of Clopidogrel and aspirin in these patients was not shown to be more effective than Clopidogrel alone, but was shown to increase major bleeding.
  • Thrombotic thrombocytopenic purpura (TTP): TTP has been reported with Clopidogrel, including fatal cases (very rarely).

[edit] INTERACTIONS

  • Avoid concomitant use with omeprazole or esomeprazole (they diminish the antiplatelet activity of clopidogrel by inhibiting the CYP2C19 isoenzyme)
  • Nonsteroidal anti-inflammatory drugs (NSAIDs): Combination use increases risk of gastrointestinal bleeding.
  • Warfarin: Combination use increases risk of bleeding

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category B (US). Reproduction studies performed in rats and rabbits at doses up to 500 and 300 mg/kg/day, respectively (65 and 78 times the recommended daily human dose, respectively, on a mg/m2 basis), revealed no evidence of impaired fertility or fetotoxicity due to clopidogrel. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of a human response, Clopidogrel should be used during pregnancy only if clearly needed.
  • Nursing Mothers: It is not known whether Clopidogrel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from clopidogrel, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

[edit] SIDE EFFECTS

Bleeding, including epistaxis (nose bleeds), gastrointestinal hemorrhage (bleeding in the stomach or gut), hematoma (bruising), and bleeding at the procedural site (where a blood vessel has been punctured), is the most commonly reported adverse reaction.

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