Clopidogrel (Plavix) | Medication Reference

Bedside Snapshot

P2Y12 Receptor Inhibitor: Irreversibly blocks ADP-mediated platelet activation; key drug for ACS, PCI stents, and ischemic stroke/TIA prevention
Dual Antiplatelet Therapy (DAPT): Almost always used with aspirin initially after ACS or stenting; may be used alone long term in some stroke/TIA patients or those with aspirin intolerance
Prodrug Activation: Requires hepatic CYP enzymes (especially CYP2C19); genetic polymorphisms and drug-drug interactions can reduce active metabolite exposure and blunt effect
Typical Dosing: 300-600 mg loading dose, then 75 mg PO daily maintenance
Persistent Effect: Platelet inhibition persists for life of platelet (~7-10 days); no direct reversal agent—reversal relies on holding drug and sometimes transfusing platelets in major bleeding
Cost & Availability: Compared to newer P2Y12 inhibitors (ticagrelor, prasugrel), clopidogrel is slightly less potent but cheaper, widely available, and often preferred in patients with higher bleeding risk

Brand & Generic Names

Generic Name: Clopidogrel bisulfate
Brand Names: Plavix, generics

Medication Class

Thienopyridine antiplatelet agent; P2Y12 receptor inhibitor

Pharmacology

Mechanism of Action:

Clopidogrel is a prodrug: requires hepatic biotransformation via CYP enzymes (CYP2C19, 3A4, 2B6, others) to an active thiol metabolite
The active metabolite irreversibly binds to the P2Y12 ADP receptor on platelets, blocking ADP-mediated activation and subsequent GPIIb/IIIa receptor expression
Prevents ADP-induced platelet aggregation, especially important in thrombus formation on disrupted atherosclerotic plaques and stents
Because inhibition is irreversible, platelets remain inhibited for their lifespan; new platelet production restores function over 7-10 days

Pharmacokinetics:

Absorption: Well absorbed orally; unaffected significantly by food
Activation: ~85% of dose hydrolyzed to inactive metabolites; ~15% metabolized to active thiol via CYP2C19 and other hepatic enzymes
Onset: With 300 mg loading dose, significant platelet inhibition at ~4-6 hours; with 600 mg loading, onset faster (~2 hours). Without loading, steady-state effect after ~3-7 days of 75 mg daily
Elimination: Inactive metabolites excreted renally (~50%) and in feces (~50%); effective half-life of active metabolite is short, but functional effect persists due to irreversible receptor binding
CYP2C19 Poor Metabolizers: Patients with genetic polymorphisms or those taking strong inhibitors (e.g., omeprazole) may have reduced response; some centers use alternative P2Y12 inhibitors in high-risk patients

Indications

Acute coronary syndrome: STEMI, NSTEMI, unstable angina with PCI and stent placement as part of DAPT
Medically managed ACS: No PCI, alongside aspirin to reduce recurrent ischemic events
Ischemic stroke or TIA: Secondary prevention, either as monotherapy or short-course DAPT initially (e.g., clopidogrel + aspirin in minor stroke/TIA per neuro guidelines)
Peripheral arterial disease: Symptomatic claudication or prior limb ischemia
Aspirin intolerance: Alternative antiplatelet agent in patients with aspirin allergy

Dosing & Administration

Available Forms:

Tablets: 75 mg (most common), 300 mg loading tablets in some markets
Crushed tablets can be given via NG/OG tube if needed; absorption remains reasonably good
Combination products with aspirin exist but are less common in acute ICU/ED setting

Adult Dosing (Always Follow Cardiology/Neuro Protocols):

Indication / Scenario	Loading Dose	Maintenance Dose	Notes
STEMI/NSTEMI with planned PCI	600 mg PO once	75 mg PO daily	Start as early as possible; 300 mg load if bleeding risk high or PCI delayed
Fibrinolytic-treated STEMI (no PCI initially available)	300 mg PO once	75 mg PO daily	Guideline-based; duration typically ≥14 days, often up to 1 year
Medically managed NSTEMI/UA (no PCI)	300-600 mg PO once	75 mg PO daily	Used with aspirin; duration often 12 months
Ischemic stroke / TIA (minor stroke, high-risk TIA)	300-600 mg PO once	75 mg PO daily	Short-course DAPT (aspirin + clopidogrel) often 21-90 days, then monotherapy
Established peripheral arterial disease	None (or 300 mg in some regimens)	75 mg PO daily	Monotherapy or in combination with aspirin per vascular/cardiology guidance
Post-stent (DES or BMS)	600 mg PO once (often given pre-PCI)	75 mg PO daily	Duration: at least 6-12 months depending on stent type and bleeding risk
Renal/hepatic impairment	Standard	75 mg PO daily	No routine dose adjustment, but bleeding risk is higher in severe disease

Contraindications

Contraindications:

Active pathological bleeding (e.g., gastrointestinal bleeding, intracranial hemorrhage)
Known hypersensitivity to clopidogrel or any component of the formulation

Major Precautions:

History of intracranial hemorrhage or major GI bleeding: weigh ischemic benefit vs bleeding risk closely
Concurrent use with other antiplatelets or anticoagulants increases bleeding risk; ensure indication is strong and duration is appropriate
CYP2C19 poor metabolizers or patients on strong CYP2C19 inhibitors (omeprazole, esomeprazole, some SSRIs) may have reduced clopidogrel effect; consider alternative P2Y12 agents in high-risk patients
Rare but serious thrombotic thrombocytopenic purpura (TTP): presents with thrombocytopenia, hemolytic anemia, neurologic signs, renal dysfunction, and fever

CYP2C19 Interactions: Omeprazole and esomeprazole significantly reduce clopidogrel activation. Consider using pantoprazole or other PPIs with less interaction when PPI therapy is needed.

Adverse Effects

Common:

Bleeding (epistaxis, bruising, ecchymoses)
Gastrointestinal upset: dyspepsia, diarrhea
Rash or pruritus

Serious:

Major bleeding: GI bleed, intracranial hemorrhage, surgical site bleeding
Thrombotic thrombocytopenic purpura (TTP)
Severe neutropenia or aplastic anemia (rare)

Monitoring

Clinical Monitoring:

Signs of bleeding: overt bleeding (GI, GU, surgical drains), declining hemoglobin/hematocrit, hemodynamic instability
Neurologic status for possible intracranial hemorrhage in setting of new or worsening neurologic deficits or severe headache
CBC and platelet count periodically in long-term therapy or if bruising/bleeding seems excessive
Review medication list for interacting drugs (especially PPIs, SSRIs, and other antithrombotics)
Timing of last dose before high-bleeding-risk procedures: typically held 5-7 days pre-op in elective surgery or neuraxial procedures

Clinical Pearls

600 mg Load for Emergent PCI: For emergent PCI in ACS, a 600 mg load provides faster and more complete platelet inhibition than 300 mg and is often preferred in the cath lab setting.

Life-Threatening Bleeding Management: If stented patient on clopidogrel has life-threatening bleed, management is mostly supportive: hold clopidogrel, transfuse platelets and blood products as needed, and involve cardiology early for stent thrombosis risk assessment.

Short-Course DAPT in Stroke/TIA: In minor stroke/TIA, short-course DAPT with aspirin and clopidogrel started early has been shown to reduce recurrent ischemic events; long-term DAPT increases bleeding and is usually avoided.

Alternative P2Y12 Inhibitors: Consider ticagrelor or prasugrel in high-risk ACS/PCI patients if bleeding risk is acceptable and cost/access allow; clopidogrel remains excellent for many lower-risk patients.

Document DAPT Duration: Always document indication and planned duration of DAPT in your notes and handoffs—this is often lost between ED, ICU, and floor transitions.

References

1. Lexicomp. (2024). Clopidogrel: Drug information. Wolters Kluwer.
2. Levine, G. N., Bates, E. R., Bittl, J. A., et al. (2016). 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease. Circulation, 134(10), e123–e155. https://doi.org/10.1161/CIR.0000000000000404
3. Kleindorfer, D. O., Towfighi, A., Chaturvedi, S., et al. (2021). 2021 Guideline for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke, 52(7), e364–e467. https://doi.org/10.1161/STR.0000000000000375