clopidogrel
Brand: Plavix
Prototype Drug
Drug Class: antiplatelet
Drug Family: antiplatelet
Subclass: P2Y12 ADP receptor antagonist (thienopyridine prodrug)
Organ Systems: cardiovascular
Mechanism of Action
Prodrug activated by CYP2C19 (and CYP3A4); active thiol metabolite irreversibly alkylates P2Y12 receptor preventing ADP-mediated platelet aggregation.
P2Y12 ADP receptor on platelets
Indications
- ACS with DAPT (dual antiplatelet therapy)
- stroke/TIA prevention
- PAD
- PCI stent thrombosis prevention
Contraindications
- active pathological bleeding
- severe hepatic impairment
Adverse Effects
Common
- bleeding
- rash
- GI upset
Serious
- major hemorrhage
- TTP (rare)
- neutropenia (rare)
Pharmacokinetics (ADME)
| Absorption | 50% absorbed; CYP2C19-dependent activation |
| Distribution | irreversible platelet binding |
| Metabolism | hepatic CYP2C19 (primary), CYP3A4 |
| Excretion | renal 50%, fecal 46% |
| Half-life | 7-10 days (platelet lifespan) |
| Onset | peak active metabolite 6h |
| Peak | peak effect 6h |
| Duration | 7-10 days |
| Protein Binding | 98% |
| Vd | variable |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| omeprazole/esomeprazole | CYP2C19 inhibition reduces active metabolite generation — may reduce efficacy | moderate |
| aspirin | synergistic antiplatelet (DAPT) | beneficial |
| NSAIDs | additive bleeding risk | major |
Nursing Considerations
- CYP2C19 poor metabolizers (15-20% of Asians, 2-4% Caucasians) have reduced antiplatelet effect — consider genotyping or alternative agent
- Hold 5-7 days before elective surgery (platelet regeneration time)
- Avoid omeprazole (use pantoprazole or famotidine if PPI needed with clopidogrel)
- DAPT: aspirin + clopidogrel for 12 months post-ACS/DES stent
Clinical Pearls
- Prodrug requiring CYP2C19 activation — poor metabolizers (loss-of-function alleles *2, *3) have reduced efficacy
- CURE trial: clopidogrel + aspirin reduced CV events in NSTEMI
- COMMIT/CLARITY-TIMI 28: benefit in STEMI
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.