NOCLOG

Indications

• Prevention of atherothrombotic events in patients with a history of myocardial infarction, stroke, or established peripheral arterial disease
• Management of acute coronary syndrome, including unstable angina and non-ST elevation myocardial infarction
• Post-stenting in patients undergoing percutaneous coronary intervention
• Secondary prevention in patients with a history of cardiovascular events

Dosage

Children: Refer to BNF for Children for specific paediatric dosing recommendations.

Adults: Refer to BNF for specific adult dosing recommendations based on clinical indications.

Mechanism of action

Clopidogrel is converted to its active metabolite by cytochrome P450 enzymes, primarily CYP2C19. The active metabolite irreversibly binds to the P2Y12 receptor on platelets, preventing ADP from activating the receptor. This action inhibits the activation of the glycoprotein IIb/IIIa complex, which is necessary for platelet aggregation.

Pharmacodynamics

The pharmacodynamic effects of clopidogrel include a dose-dependent inhibition of platelet aggregation. The onset of action occurs within 2 hours of administration, with peak antiplatelet effects typically observed within 3 to 7 days of continuous use. The duration of action can persist for up to 5 days after discontinuation due to the irreversible binding of the drug to the P2Y12 receptor.

Pharmacokinetics

Clopidogrel is rapidly absorbed following oral administration, with peak plasma concentrations reached within 1 to 2 hours. It has a bioavailability of approximately 50%. The drug undergoes extensive hepatic metabolism, primarily via CYP2C19, leading to the formation of its active metabolite. The elimination half-life of clopidogrel is about 6 hours, but this can be prolonged due to its active metabolite's effects. Clopidogrel and its metabolites are primarily excreted in the urine.

Contra-indications

• Active bleeding such as peptic ulcer or intracranial hemorrhage
• Severe liver impairment
• Hypersensitivity to clopidogrel or any component of the formulation

Adverse effects

• Bleeding complications including hematoma, ecchymosis, and gastrointestinal bleeding
• Thrombocytopenic purpura
• Diarrhea
• Rash
• Nausea
• Headache
• Dizziness
• Fatigue

Interactions

• CYP2C19 inhibitors such as omeprazole may reduce the effectiveness of clopidogrel
• Concurrent use with anticoagulants (e.g., warfarin) increases bleeding risk
• NSAIDs may increase the risk of gastrointestinal bleeding
• Thrombolytics may increase the risk of bleeding when used together

Precautions

• Use with caution in patients with a history of bleeding disorders
• Monitor for signs of bleeding, especially in the elderly or those with renal impairment
• Discontinue use prior to surgical procedures due to increased bleeding risk

Pregnancy

Clopidogrel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data are available on its safety in pregnant women.

Breast-feeding

It is not known whether clopidogrel is excreted in human milk. Caution should be exercised when clopidogrel is administered to a nursing woman.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets: 75 mg, 300 mg