see also:

• antiplatelet agents

• platelet aggregation inhibitor used in prophylaxis of thromboembolic disorders and with aspirin (acetylsalicylic acid) in acute coronary syndrome
• marketed as Plavix and Iscover.
• prodrug that requires hepatic metabolism (partly by CYP2C19) to become biologically active as a platelet inhibitor.

• acute coronary syndromes:
  • if age < 75yrs and not going for PCI, then 300 mg loading dose then 75 mg once daily (with aspirin)
  • if patient going to PCI:
    • 600mg loading dose as anti-platelet effects by 2hrs, compared with 300mg dose onset of effect is 6 hours.
    • ongoing dosing post PCI: 150mg daily for 7 days then 75mg/d for at least 12 months ²⁾
  • HOWEVER, giving clopidogrel MAY delay CABG if this is needed as it increases bleeding and mortality if given within 5 days of CABG!
• TIA or minor stroke in patients who have had haemorrhage excluded:
  • dual antiplatelet therapy (DAPT)
    • clopidogrel (initial dose 300 mg, followed by 75 mg per day) plus aspirin (initial dose 300 mg followed by 75 mg per day for 21 days - but no aspirin if high bleeding risk)
    • then after 21 days, clopidogrel 75 mg, once daily monotherapy, as long-term, maintenance dose
  • NB. for those with PU or GORD, add a PPI such as pantoprazole or lansoprazole, as other PPI’s, including omeprazole, are known to reduce the efficacy of clopidogrel.
  • NB. if poor metabolizer of clopidogrel, consider ticagrelor 90mg twice daily for 21 days instead of clopidogrel then change to dipyridamole MR 200mg twice daily plus aspirin 75mg once daily³⁾

• severe hepatic impairment
• active pathological bleeding
• lactation

• monitor for bleeding
• bleeding risk incl surgery, trauma, intraocular or GI lesion; elective surgery (may discontinue greater than or equal to 5 days prior if antiplatelet effect not desired);
• coronary artery bypass (interrupt therapy greater than or equal to 5 days prior);
• moderate hepatic, severe renal impairment;
• acute ischaemic stroke (< 7 days);
• elderly greater than or equal to 75 yrs;
• pregnancy, children < 18 yrs

• bleeding
• blood dyscrasias
• thrombotic thrombocytopenic purpura (very rare)
• fatigue
• rash incl bullous dermatitis

• some patients have genetic polymorphisms which reduce CYP2C19 function⁴⁾ and thus result in diminished anti-platelet effectiveness whilst others are poor metabolizers and may have increased bleeding risk
  • ~25% of Europeans are ultra-fast metabolizers
  • 20-30% of European populations may have impaired metabolism of clopidogrel
  • 50-60% of East Asian populations may have impaired metabolism of clopidogrel
  • 30-46% of some South Asian populations may have impaired metabolism of clopidogrel
• some drugs inhibit CYP2C19 and thus may reduce anti-platelet effectiveness including:
  • proton pump inhibitors (PPIs) - especially omeprazole
• CYP2C9 substrates incl phenytoin, tamoxifen, tolbutamide, fluvastatin
• other medications that increase bleeding risk:
  • aspirin (acetylsalicylic acid); heparin, thrombolytics; glycoprotein IIb/IIIa inhibitors; warfarin; non-steroidal anti-inflammatory drugs (NSAIDs)