Clopidogrel

Overview

Clopidogrel is an oral antiplatelet medicine in the thienopyridine class that reduces the risk of blood clots by irreversibly blocking the platelet P2Y₁₂ ADP receptor. By preventing ADP-mediated activation of the glycoprotein IIb/IIIa complex, clopidogrel inhibits platelet aggregation for the lifespan of the platelet (~7–10 days). It is a prodrug that requires hepatic biotransformation via cytochrome P450 enzymes (notably CYP2C19) into its active thiol metabolite. This activation step partly explains response variability between patients.

In contemporary cardiovascular care, clopidogrel is used to prevent arterial thrombotic events in people with atherosclerotic disease, including after heart attack, ischaemic stroke or transient ischaemic attack (TIA), and following percutaneous coronary intervention (PCI) with stent placement. It is also used in symptomatic peripheral arterial disease and as an alternative to aspirin in those who are intolerant. In many clinical pathways, clopidogrel is combined with aspirin as dual antiplatelet therapy (DAPT) for a defined period to protect new coronary stents and reduce recurrent events; later, most patients continue with a single antiplatelet agent long-term.

Because clopidogrel modifies haemostasis, its major safety consideration is bleeding. The balance between protection from thrombosis and bleeding risk is individualised, taking into account age, weight, history of bleeding or stroke, concomitant medicines (e.g., anticoagulants, NSAIDs), and procedural needs (e.g., planned surgery or endoscopy). Patients are counselled to report signs of bleeding early and to communicate use of clopidogrel to all healthcare providers and dentists.

Interactions

Because clopidogrel is a CYP-metabolised prodrug and an antiplatelet, interactions are both pharmacokinetic and pharmacodynamic:

May reduce clopidogrel activation (use with caution)

• Strong CYP2C19 inhibitors: Omeprazole, esomeprazole, fluvoxamine, fluoxetine, ticlopidine. These can blunt formation of the active metabolite. If gastroprotection is needed, many guidelines prefer pantoprazole over omeprazole/esomeprazole.
• Other inhibitors/competitive substrates: Cimetidine, ketoconazole, voriconazole. Clinical significance varies; monitor.

Increase bleeding risk (additive effects)

• Anticoagulants: Warfarin, DOACs (apixaban, rivaroxaban, dabigatran, edoxaban).
• Other antiplatelets/NSAIDs: Aspirin, ibuprofen, naproxen, ketorolac; SSRIs/SNRIs also modestly increase bleeding risk by affecting platelet serotonin.
• Systemic corticosteroids and alcohol: Raise GI bleed risk; consider gastroprotection.

Other considerations

• Opioids (e.g., morphine): Can delay absorption and reduce peak exposure of oral P2Y₁₂ inhibitors in ACS; clinical teams may adjust loading strategy.
• Herbal products/supplements: Ginkgo, garlic, ginseng, fish-oil in high doses may increase bleeding risk. St John’s wort may induce metabolism and impact response.

Provide a complete list of medicines and supplements to your clinician and pharmacist. Avoid new OTC NSAIDs without advice.

Overdose / Missed Dose

Overdose: Main concern is bleeding. There is no specific antidote to reverse clopidogrel’s platelet inhibition. Management is supportive: local measures for minor bleeding; in serious bleeding, consider platelet transfusion (new platelets are not inhibited), tranexamic acid, and specialist care. Activated charcoal may help if ingestion was very recent.

Accidental double dose: Usually no immediate danger in otherwise stable patients, but monitor for bruising, nosebleeds, gum bleeding, or black stools. Skip the next dose if advised and contact a clinician or pharmacist for personalised guidance.

Missed dose: Take as soon as remembered the same day; if the next dose is due soon, skip the missed dose—do not double up. In the early weeks after stent placement or ACS, adherence is critical; if more than one dose is missed, contact your cardiology team promptly.

Always carry your medicine list. In an emergency, inform clinicians you take clopidogrel to guide safe treatment.

Storage

• Store at room temperature (typically 15–25 °C), protected from moisture and direct heat.
• Keep tablets in the original blister until use to protect from humidity and to retain batch/expiry information.
• Keep out of sight and reach of children.
• Do not use after the expiry date. Return unused tablets to a pharmacy take-back scheme.

When travelling, keep clopidogrel in hand luggage in its original labelled packaging and carry a medication list; abrupt interruption without medical advice may be hazardous after coronary stenting.