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Metabolization of Clopidogrel

Clopidogrel is a platelet antiaggregant analogous to ticlopidine (thienopyridine). It is a prodrug that needs to be pre-processed to be effective and its mechanism of action consists in preventing platelet aggregation by inhibiting the binding of ADP to its platelet receptor and the subsequent activation of the ADP-mediated GPIIb-IIIa complex.

CONTRAINDICATIONS

Hypersensitivity.

Severe hepatic impairment, active pathological haemorrhage (peptic ulcer or intracranial hemorrhage).

CAUTIONS:

Caution should be exercised when prescribing clopidogrel in the following cases:

Patients at risk of bleeding from trauma, surgery, gastrointestinal, intraocular lesions, etc., since it increases the risk of bleeding if administered together with: acetyl salicylic acid, heparin, glycoprotein IIb / IIIa inhibitors, NSAIDs, SSRIs and others medications such as pentoxifylline, thrombolytics and oral anticoagulants.

Discontinuation of clopidogrel therapy is recommended 7 days prior to surgery.

Cautions should be taken with patients at risk for: thrombotic thrombocytopenic purpura (mortal) and hemophilia acquired following administration of clopidogrel (discontinuation of therapy is highly recommended), allergic cross reactivity (assessing if there is a history of hypersensitivity to thienopyridines and monitoring during treatment).

Precaution in patients with renal impairment and moderate hepatic impairment.

Do not use this drug in children or adolescents. The treatment with clopidogrel is not recommended during the 7 days after suffering an acute ischemic cerebral infarction.

Clopidogrel is not recommended for concomitant treatment with substrates of CYP2C8 (prepaglinide, paclitaxel).

SIDE EFFECTS

Hematoma, epistaxis, gastrointestinal bleeding, diarrhea, abdominal pain, dyspepsia and bleeding in the place of injection.

PHARMACOLOGIC INTERACTIONS:

Clopidogrel is not recommended in combination with potent or moderate CYP2C19 inhibitors (omeprazole, esomeprazole, fluvoxamine, fluoxetine, moclobemide, voriconazole, fluconazole, ticlopidine, carbamazepine, efavirenz) as they may lead to a reduction in the levels of the active metabolite of clopidogrel.

BRAND NAMES:

  • Agrelan ®
  • Clopidogrel ®
  • Iscover ®
  • Maboclop ®
  • Plavix ®
  • Vatoud ®
  • Zyllt ®

Gene or region studied

  • CYP2C19
  • ABCB1
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