Oskela
Get started

Drug Reference

clopidogrel

antiplatelet agent· Brands: Plavix, Iscover, Clopidogrel WinthropPO

Mechanism of action
Clopidogrel is a prodrug that is activated in the liver to an active metabolite. It irreversibly inhibits the P2Y12 subtype of ADP receptors on platelet surfaces, preventing ADP-mediated activation of the glycoprotein IIb/IIIa complex and thereby inhibiting platelet aggregation for the lifespan of the platelet (7-10 days).
Pharmacokinetics
Clopidogrel is well absorbed after oral administration, but extensive first-pass metabolism results in low systemic exposure to the parent drug. It is metabolised by CYP2C19 to the active thiol metabolite. Peak plasma concentrations of the active metabolite occur about 30-60 minutes after dosing. The parent compound and metabolites are bound to plasma proteins. Elimination is mainly via urine (50%) and faeces (46%). The half-life of the active metabolite is about 30 minutes, but the antiplatelet effect persists for the platelet lifetime.
Indications & dosing

Acute coronary syndrome (unstable angina, NSTEMI, STEMI) - loading dose

Give as a single loading dose at presentation. Use 300 mg if no PCI, 600 mg if primary PCI planned.

  • adult · PO: 300–600 mg once · Give as a single loading dose at presentation. Use 300 mg if no PCI, 600 mg if primary PCI planned.

Acute coronary syndrome (unstable angina, NSTEMI, STEMI) - maintenance

Start maintenance 75 mg daily after loading dose. Continue indefinitely unless contraindicated.

  • adult · PO: 75 mg once daily · Start maintenance 75 mg daily after loading dose. Continue indefinitely unless contraindicated.

Ischaemic stroke or transient ischaemic attack - secondary prevention

No loading dose usually required; start 75 mg daily.

  • adult · PO: 75 mg once daily · No loading dose usually required; start 75 mg daily.

Symptomatic peripheral arterial disease - secondary prevention

Start 75 mg daily to reduce atherothrombotic events.

  • adult · PO: 75 mg once daily · Start 75 mg daily to reduce atherothrombotic events.
Contraindications & precautions
  • Active pathological bleeding (e.g., peptic ulcer, intracranial haemorrhage) · Clopidogrel increases bleeding risk and is contraindicated in any active bleeding.
  • Hypersensitivity to clopidogrel or any excipient · Hypersensitivity reactions including angio-oedema have been reported.
  • Severe hepatic impairment · Clopidogrel is a prodrug requiring hepatic activation; use caution in severe hepatic disease.
  • Caution in patients at increased risk of bleeding (e.g., trauma, surgery, concurrent anticoagulants or NSAIDs)
  • Caution in patients with hepatic impairment; avoid in severe hepatic disease
  • Caution in patients with CYP2C19 poor metabolizer status; consider alternative antiplatelet therapy
  • Caution in patients with a history of bleeding disorders or recent ischaemic stroke
  • Monitor for signs of bleeding, including occult gastrointestinal bleeding, during therapy
Adverse effects
  • Bleeding (including gastrointestinal, intracranial, and epistaxis)serious
  • Bruising and haematoma
  • Diarrhoea
  • Abdominal pain and dyspepsia
  • Rash and pruritus
  • Thrombotic thrombocytopenic purpura (TTP)serious
  • Neutropenia and agranulocytosisserious
  • Aplastic anaemiaserious
  • Stevens-Johnson syndrome and toxic epidermal necrolysisserious
Interactions
  • ibuprofenmajorAvoid the combination if possible. Consider alternative analgesics such as paracetamol or a selective COX-2 inhibitor, depending on the clinical context. If an NSAID is necessary, use the lowest effective dose for the shortest duration, and consider gastroprotection with a proton pump inhibitor (e.g., omeprazole or pantoprazole). Monitor patients for signs of gastrointestinal bleeding (e.g., melaena, haematemesis) and for reduced antiplatelet efficacy. Advise patients to report any unusual bleeding or bruising. Note that the interaction may be less pronounced with ibuprofen doses taken intermittently or after clopidogrel administration, but the safest approach is to avoid concurrent use.
  • omeprazolemajorAvoid the combination. If gastroprotection is required, consider an H2-receptor antagonist such as famotidine or a proton pump inhibitor with less CYP2C19 inhibition, such as pantoprazole. If omeprazole is considered necessary, weigh the risk of reduced clopidogrel efficacy and monitor for signs of thrombotic events, but no reliable laboratory measure exists to adjust therapy.
  • esomeprazolemajorAvoid co-prescription when possible. If a proton pump inhibitor is needed, consider using pantoprazole, which has minimal CYP2C19 inhibition, or an alternative antiplatelet agent such as ticagrelor or prasugrel. If the combination is considered necessary, monitor patients closely for signs of cardiovascular events and assess platelet function if available.
  • warfarinmajorAvoid concomitant use unless the benefit clearly outweighs the bleeding risk and no alternative exists. If combination therapy is considered essential, use the shortest possible duration, monitor INR frequently, and closely observe for signs of bleeding. Consider gastroprotection with a proton pump inhibitor (e.g., omeprazole or pantoprazole) in patients at risk of gastrointestinal bleeding. If invasive procedures or surgery are planned, the combination should be stopped appropriately in advance.
  • aspirinmajorWhen prescribed for a valid indication, use the lowest effective doses (e.g., aspirin 75-100 mg daily and standard clopidogrel maintenance). Monitor for signs of bleeding, and consider gastroprotective strategies such as a proton pump inhibitor, especially in patients at high risk. Avoid concurrent use of other anticoagulants or antiplatelets without careful assessment. Contraindicated in active pathological bleeding or when the patient has a severe bleeding disorder.
  • fluoxetinemoderateIf concomitant use is necessary, consider an alternative SSRI that is less likely to inhibit CYP2C19 (e.g., sertraline, citalopram), or use an alternative P2Y12 inhibitor (e.g., prasugrel or ticagrelor) if clinically appropriate. Monitor for signs of bleeding and thrombotic events. Where possible, prescribe the lowest effective dose of fluoxetine and regularly review the combination.
  • apixabanmajorAvoid the combination unless there is a clear indication for dual antithrombotic therapy as recommended by guidelines. If co-prescription is necessary, use the lowest effective doses and the shortest duration. Monitor closely for signs of bleeding (e.g., dark stools, haematuria, bruising) and check haemoglobin and haematocrit periodically. Consider omeprazole or other gastroprotective agents. Assess renal function and adjust apixaban dose accordingly.
  • rivaroxabanmajorAvoid concomitant use unless the clinical benefit outweighs the bleeding risk. If the combination is necessary, use the lowest effective doses of both agents, monitor the patient closely for signs of bleeding, and consider using a proton pump inhibitor for gastroprotection. Regularly review the ongoing need for dual therapy.
  • dabigatranmajorAvoid co-prescription unless the benefit clearly outweighs the risk, such as in specific cardiac indications. If combined, use the lowest effective doses, monitor closely for signs of bleeding, and consider gastroprotective therapy. Perform regular full blood counts and renal function tests.
  • edoxabanmajorAvoid the combination unless the anticipated benefit outweighs the risk. When co-prescription is necessary, use the lowest effective doses and limit the duration of dual therapy. Monitor the patient closely for signs of bleeding, including haemoglobin and haematocrit checks, and assess for occult blood loss. Consider using a proton pump inhibitor for gastroprotection. Evaluate renal function regularly and adjust edoxaban dose as needed. Review the indication for clopidogrel at each visit and discontinue when no longer required.
Renal & hepatic adjustment
  • Hepatic impairment (severe): No dosage adjustment, but use with caution. Monitor for bleeding.
Monitoring, pregnancy & toxicity
  • Signs of bleeding · Ongoing
  • Haemoglobin · Periodic if bleeding suspected
  • Pregnancy: Use only if potential benefit justifies risk to fetus. Limited data; consider alternative antiplatelet agent.
  • Toxicity: Bleeding, bruising, epistaxis, GI bleeding · Discontinue drug. Supportive care. For severe bleeding, consider platelet transfusion.
Clinical notes
Clopidogrel is used to prevent thrombotic events in patients with recent myocardial infarction, recent ischaemic stroke, or established peripheral arterial disease. It is also used in combination with aspirin for acute coronary syndrome and after percutaneous coronary intervention. The standard maintenance dose is 75 mg once daily; a loading dose of 300 mg or 600 mg may be given. Because it is a prodrug, patients with reduced CYP2C19 activity (e.g., poor metabolisers) may have higher residual platelet reactivity, though routine genetic testing is not universally recommended. Clopidogrel increases bleeding risk; it should be discontinued 5 days before elective surgery. It is contraindicated with active bleeding. Regional formulary guidance may vary regarding use as first-line antiplatelet versus alternatives like ticagrelor or prasugrel.

Log in to read the full clopidogrel monograph

A free account unlocks the complete drug reference, the interaction checker, prescription practice and every other learning tool.

Log inCreate a free account

BNF; local formulary