Makindo Medical Notes

⚠️ Important: Clopidogrel is a prodrug that requires activation by hepatic CYP450 (especially CYP2C19). Delayed onset of full platelet inhibition may occur (~48 hours without a loading dose). Always consult cardiology before stopping dual antiplatelet therapy (DAPT) after PCI or ACS.

📖 About

• Clopidogrel is a thienopyridine antiplatelet agent, a selective and irreversible P2Y₁₂ ADP receptor blocker on platelets.
• It prevents ADP-mediated platelet activation and aggregation.
• Works synergistically with aspirin in dual antiplatelet regimens.
• Always check the BNF for current dosing guidance.

⚙️ Mode of Action

• Clopidogrel is a prodrug requiring hepatic activation (CYP2C19-dependent).
• Irreversibly blocks platelet P2Y₁₂ receptors → prevents ADP binding and downstream GP IIb/IIIa activation.
• Effect lasts for the lifespan of the platelet (~7–10 days).
• Bleeding time is prolonged.

🩺 Indications (NICE/BNF)

• Acute coronary syndrome (ACS): with aspirin for up to 12 months (NSTEMI, unstable angina, STEMI).
• Post-PCI with stenting:
  • Bare-metal stent: minimum 1 month DAPT (aspirin + clopidogrel).
  • Drug-eluting stent: at least 12 months DAPT (unless bleeding risk dictates otherwise).
• Secondary prevention: after ischaemic stroke, TIA, or in established peripheral arterial disease (75 mg OD).
• Aspirin intolerance: as alternative single antiplatelet therapy.

💊 Dosing – Clopidogrel (verify with BNF/datasheet)

🚫 Contraindications

• Active bleeding (e.g. GI haemorrhage, intracranial haemorrhage).
• Severe hepatic impairment.
• Known hypersensitivity.
• Caution in trauma, planned surgery, or thrombocytopenia.

❗ Side Effects

• GI upset: dyspepsia, diarrhoea, abdominal pain.
• Rash, pruritus, bleeding (major bleeding risk ~1%).
• Rare but serious: thrombotic thrombocytopenic purpura (TTP) with microangiopathic haemolysis.
• Bruising, epistaxis, prolonged bleeding time.

🔄 Interactions

• PPIs: Omeprazole and esomeprazole ↓ efficacy (avoid). Use lansoprazole or pantoprazole if gastroprotection required.
• Other anticoagulants / antiplatelets: additive bleeding risk.
• CYP2C19 inhibitors (e.g. fluoxetine, fluvoxamine): may ↓ clopidogrel activation.

📚 References

• Summary of Product Characteristics
• NICE CG94: ACS: Unstable angina and NSTEMI
• NICE TA210: Clopidogrel and modified-release dipyridamole for vascular disease