Plavix
Plavix
Generic Name
Plavix
Mechanism
- Irreversible inhibition of the *P2Y12* ADP receptor on platelet surfaces.
- Prevents GPIIb/IIIa conformational change → ↓ platelet aggregation.
- Requires hepatic CYP2C19 activation; parent drug is inactive.
- Antagonizes platelet activation triggered by ADP, thrombin, and collagen pathways.
- Effect onset 30‑60 min after dose, with maximal platelet inhibition after ~6 h; duration ≈ 5‑7 days due to irreversible binding.
Pharmacokinetics
| Parameter | Typical Value |
| Absorption | Oral, 70‑80 % bioavailability; GI pH‑dependent absorption; peak plasma 1–3 h post‑dose. |
| Metabolism | Hepatic via CYP2C19, CYP3A4, CYP1A2; active 2‑OH‑clopidogrel metabolite. |
| Half‑life | 20 min (parent) → 8–12 h (active metabolite). |
| Elimination | 60 % renal, 15 % fecal; 40 % via hepatic excretion. |
| Drug interactions | Strong CYP2C19 inhibitors (ketoconazole, clarithromycin) ↑ plasma levels; P‑gp substrates (digoxin) may be affected. |
Indications
- Acute coronary syndrome (ACS) – secondary prevention (1 year; may be extended with dual antiplatelet therapy, DAPT).
- Percutaneous coronary intervention (PCI) with stent implantation – dual therapy with aspirin + clopidogrel for 6 months (drug-eluting stent) or 12 months (bare‑metal stent).
- Stable coronary artery disease (CAD) – secondary prevention in patients on dual antiplatelet therapy when aspirin intolerant.
- Carotid artery stenting – dual antiplatelet therapy for 6–12 weeks.
- Ischemic stroke (non–cardioembolic) – dual therapy after intracranial stenting or in specific high‑risk patients.
- Peripheral arterial disease – used off‑label for long‑term secondary prevention. |
Contraindications
- Active pathological bleeding (stroke, GI bleed, intracranial hemorrhage).
- Plow‑grade platelet function (e.g., HLA‑B*5701 carriers – all‑opurinol hypersensitivity – *note*: cross‑reactivity with clopidogrel).
- Severe hepatic impairment (due to CYP metabolism).
- Known hypersensitivity to clopidogrel or any excipient.
- Use caution:
- Pregnancy: Class B; risks not established.
- Childbearing: Low risk but avoid when possible.
- Chronic kidney disease: Dialysis patients may need dose adjustment.
Dosing
| Situation | Dose | Schedule | Comments |
| Initial loading dose | 300–600 mg oral | Single dose | Rapid platelet inhibition. |
| Maintenance (stable) | 75 mg daily | Oral | Continuous therapy. |
| Post‑PCI (stable) | 75 mg daily | Oral | DAPT with aspirin. |
| Acute coronary syndrome | 600 mg loading, then 75 mg daily | Oral | Dual therapy for 12 months (beyond 12 months consider individual risk). |
| Intubated/IV | 600 mg IV (rare) | Single dose |
*Adjust for age or concomitant therapy as clinical scenarios dictate.*
Adverse Effects
- Bleeding (most serious): GI, intracranial, mucosal, surgical bleeding. Rate ~6 %–10 % in high‑risk cohorts.
- Reversible bruising, epistaxis, hematuria.
- Allergic reactions: rash, pruritus, anaphylaxis (rare).
- Drug‑induced thrombocytopenia (very uncommon).
- Metabolic: rarely ↑ liver enzymes (monitor in hepatic disease).
Monitoring
| Parameter | Frequency | Rationale |
| Platelet function tests (VerifyNow, LTA) | Before therapy & when bleeding risk increases | Detect clopidogrel resistance. |
| Hemoglobin/hematocrit | Baseline, 1–2 weeks, then monthly if bleeding | Monitor anemia. |
| Liver enzymes | Baseline, at 1 month, then as clinically indicated | Liver function. |
| Renal function | Baseline | Dose adjustment for CKD stage 3–5. |
| Bleeding signs | Continuous | Prompt intervention. |
Clinical Pearls
- Genetic testing: HLA‑B*5701 screening improves safety in patients with a known history of hypersensitivity to clopidogrel or other thienopyridines.
- Drug interactions: Co‑administration with proton pump inhibitors (PPIs) like omeprazole may reduce clopidogrel activation; use PPIs sparingly or choose *rabeprazole*.
- Switch to ticagrelor: For patients with clopidogrel resistance or requiring higher platelet inhibition (e.g., high‑risk ACS), ticagrelor is an effective alternative, though it carries a higher dyspnea risk.
- Platelet‐rich plasma: Clopidogrel’s effect persists for up to 7 days; a platelet transfusion in emergent bleeding may still not reverse inhibition quickly.
- Age adjustment: Older adults (>65 y) have higher bleeding risk; consider dose reduction if possible, particularly if on other anticoagulants.
- Post‑stent bleeding risk: Dual therapy beyond 6 months with stents can be shortened in high‑bleeding risk individuals; consider clopidogrel 75 mg daily + aspirin 81 mg daily for 3–6 months, then aspirin alone.
- Kidney disease: For Stage 4–5 CKD (eGFR <30 mL/min), clopidogrel remains safe but monitor for bleeding; no dose adjustment required for most CKD stages.
--
• Key Takeaway: *Plavix* is a cornerstone of dual antiplatelet therapy, widely used after PCI and in ACS. Understanding its metabolism, interaction profile, and the balance between thrombotic and bleeding risks is essential for safe and effective prescribing.