Drug Name
Generic Name
Clopidogrel
Brand Name(s)
- Pakistan: Plavix
- India: Plavix, Clopilet
- US: Plavix
- UK: Plavix
Pharmacological Class
Class
Antiplatelet Agent
Subclass
P2Y12 Platelet Inhibitor
Mechanism of Action
Clopidogrel is a prodrug that requires hepatic biotransformation to its active metabolite. It irreversibly inhibits the P2Y12 component of ADP receptors on the platelet surface, which prevents activation of the GPIIb/IIIa receptor complex, thereby reducing platelet aggregation.
Indications
Primary Indications
Reduction of atherothrombotic events in patients with acute coronary syndrome (ACS), recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease.
Off-label Uses
Clopidogrel may be used off-label for the prevention of thrombosis in patients with atrial fibrillation who are not candidates for oral anticoagulants, and in combination with aspirin for certain high-risk patients.
Dosage and Administration
Standard Dosage
The standard dosage for adults is 75 mg once daily. For acute coronary syndrome, an initial loading dose of 300-600 mg may be followed by 75 mg daily.
Route of Administration
Oral
Special Populations
- Pediatric: Safety and efficacy have not been established.
- Geriatric: No dosage adjustment necessary but increased monitoring may be required.
- Hepatic Impairment: Use with caution due to potential increased exposure to the active metabolite.
Pharmacokinetics
Absorption
Clopidogrel is rapidly absorbed after oral administration, with peak plasma concentrations of the active metabolite occurring approximately 1 hour after dosing.
Distribution
The active metabolite is approximately 98% plasma protein bound.
Metabolism
Clopidogrel is extensively metabolized by the liver, primarily by CYP2C19, with contributions from CYP3A4, CYP2B6, and other isoenzymes.
Excretion
Clopidogrel and its metabolites are excreted in the urine (50%) and feces (46%).
Half-life
The half-life of the active metabolite is approximately 8 hours.
Contraindications
Clopidogrel is contraindicated in patients with active pathological bleeding, such as peptic ulcer or intracranial hemorrhage, and in those with a known hypersensitivity to clopidogrel or any component of the product.
Warnings and Precautions
Patients should be advised of the risk of bleeding, including gastrointestinal and intracranial bleeding. Clopidogrel should be used with caution in patients with a history of bleeding disorders or those undergoing surgery. Genetic differences in metabolism may affect the drug's efficacy; patients with reduced CYP2C19 function may experience diminished antiplatelet effects.
Side Effects
Common Side Effects
Bleeding, bruising, rash, and diarrhea.
Serious Side Effects
Severe bleeding, thrombotic thrombocytopenic purpura (TTP), liver dysfunction, and hypersensitivity reactions including anaphylaxis.
Drug Interactions
Major Interactions
Proton pump inhibitors (e.g., omeprazole) can reduce the effectiveness of clopidogrel by inhibiting CYP2C19. Concurrent use should be avoided or alternatives considered.
Moderate Interactions
Other antiplatelet agents, anticoagulants, NSAIDs, and SSRIs/SNRIs may increase the risk of bleeding.
Minor Interactions
Fluoxetine and fluvoxamine may also inhibit CYP2C19 and reduce clopidogrel's effectiveness.
Pregnancy and Lactation
Pregnancy Category
Category B: No adequate and well-controlled studies in pregnant women. Clopidogrel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Breastfeeding Considerations
It is not known whether clopidogrel is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when clopidogrel is administered to a nursing woman.
Patient Counseling Information
Patients should be informed about the importance of adherence to prescribed doses, potential side effects, and the need for regular follow-up visits. They should be advised to report any unusual bleeding or bruising, and to avoid activities that may increase the risk of injury. Patients should also be aware of potential drug interactions and to consult their healthcare provider before taking any new medications or supplements.