Clognil

Approved Indications:

• Acute Coronary Syndrome (ACS):
• Unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI), in combination with aspirin.
• ST-elevation myocardial infarction (STEMI), with or without thrombolytics.
• Recent Myocardial Infarction (MI), Stroke, or Established Peripheral Arterial Disease:
• To reduce the risk of atherothrombotic events (secondary prevention).
• Post–Percutaneous Coronary Intervention (PCI):
• To prevent stent thrombosis and recurrent ischemic events.

Clinically Accepted Off-Label Uses:

• Ischemic Stroke (Minor) or Transient Ischemic Attack (TIA):
• Dual antiplatelet therapy (DAPT) with aspirin for short duration (e.g., 21 days).
• Peripheral Arterial Revascularization:
• Prevent restenosis or thrombosis.
• Coronary artery bypass graft (CABG):
• To prevent graft occlusion in selected high-risk patients.

Adults:

• ACS (UA/NSTEMI):
• Loading dose: 300 mg orally once
• Maintenance: 75 mg orally once daily
• STEMI:
• Loading: 300–600 mg (preferred in PCI)
• Maintenance: 75 mg daily, with aspirin
• Post-MI, Stroke, PAD:
• 75 mg once daily

Pediatrics:

• Not routinely recommended due to limited data.

Elderly:

• No dose adjustment required, but bleeding risk should be assessed.

Renal Impairment:

• No dose adjustment; monitor for bleeding in severe impairment.

Hepatic Impairment:

• Use with caution in moderate impairment; avoid in severe liver disease due to bleeding risk.

Administration Route:

• Oral. Administer with or without food.

Clopidogrel bisulphate is a prodrug that undergoes hepatic biotransformation, primarily via the CYP2C19 enzyme, to its active thiol metabolite. This metabolite irreversibly binds to the P2Y₁₂ class of ADP receptors on platelet surfaces, inhibiting ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. As a result, platelet aggregation is prevented. This inhibition persists for the lifespan of the platelet (approximately 7–10 days), thereby reducing the formation of arterial thrombi in conditions like atherosclerosis and acute coronary syndromes.

• Absorption: Rapid after oral administration; peak plasma levels in ~1 hour
• Bioavailability: ~50% due to first-pass metabolism
• Metabolism: Hepatic; two-step activation via CYP enzymes (mainly CYP2C19, also CYP3A4, CYP1A2, CYP2B6)
• Active Metabolite: Irreversibly binds to platelet P2Y₁₂ receptor
• Half-life: Parent compound ~6 hours; active metabolite ~30 minutes
• Elimination: ~50% renal (as inactive metabolites), ~46% fecal
• Onset of Action: Within 2 hours (faster with loading dose)
• Duration: Platelet inhibition lasts 5–7 days

• Pregnancy:
• FDA Category B (older classification). Animal studies have not shown harm; human data are limited. Use only if clearly needed.
• Lactation:
• Unknown if excreted in breast milk. Due to potential for serious adverse effects in the nursing infant, consider discontinuation of drug or breastfeeding.

• Primary Class: Antiplatelet Agent
• Subclass: P2Y₁₂ ADP Receptor Inhibitor (Thienopyridine Class)

• Known hypersensitivity to clopidogrel or any excipients
• Active pathological bleeding (e.g., gastrointestinal bleeding, intracranial hemorrhage)
• Severe hepatic impairment
• Suspected thrombotic thrombocytopenic purpura (TTP)
• Concomitant use of strong CYP2C19 inhibitors (e.g., omeprazole) may reduce efficacy

• Bleeding Risk: Use with caution in patients at risk of bleeding (e.g., trauma, surgery, peptic ulcer)
• Poor Metabolizers: Reduced effectiveness in patients with CYP2C19 loss-of-function alleles; consider genotyping
• Thrombotic Thrombocytopenic Purpura (TTP): Rare but potentially fatal; monitor for thrombocytopenia and hemolytic anemia
• Hypersensitivity Reactions: Includes rash, angioedema, or anaphylaxis
• Recent Surgery or Trauma: Discontinue 5–7 days prior to elective procedures with bleeding risk
• Combination with Other Antiplatelets or Anticoagulants: Increases risk of bleeding; monitor closely

Common Side Effects:

• Gastrointestinal: Dyspepsia, abdominal pain, diarrhea
• Hematologic: Easy bruising, epistaxis, minor bleeding
• Skin: Rash, pruritus

Serious Side Effects:

• Major bleeding (GI bleeding, intracranial hemorrhage)
• Thrombotic thrombocytopenic purpura (TTP)
• Neutropenia, agranulocytosis (rare)
• Hypersensitivity (angioedema, anaphylaxis)

Rare Effects:

• Liver enzyme elevation
• Aplastic anemia
• Eosinophilic pneumonia

• CYP2C19 Inhibitors (e.g., omeprazole, esomeprazole): Reduce clopidogrel activation → decreased efficacy
• NSAIDs, anticoagulants, other antiplatelet agents: Additive bleeding risk
• SSRIs/SNRIs (e.g., sertraline, fluoxetine): Increased bleeding risk
• Warfarin: Increased INR and bleeding risk
• Rifampin: Induces metabolism → reduced effect
• Alcohol: Potential GI irritation and bleeding

• AHA/ACC/ESC Guidelines (2023):
• Clopidogrel remains a recommended agent for dual antiplatelet therapy (DAPT) in ACS and post-PCI patients.
• Genotype-guided therapy is encouraged in high-risk patients.
• FDA Warning: Reinforced concern about reduced efficacy in CYP2C19 poor metabolizers.
• DAPT Duration Adjustment: Shorter durations (3–6 months) may be acceptable in high bleeding risk settings.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C
• Humidity & Light: Store in a dry place, protected from light and moisture
• Handling: Keep tablets in original blister pack until use
• Reconstitution: Not applicable