Clopidogrel is a prodrug, which is activated in two steps, first by CYP2C19, CYP1A2 and CYP2B6, then by CYP2C19, CYP2C9, CYP2B6 and CYP3A. The active metabolite then specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor, which is important in activation of platelets and eventual cross-linking by the protein fibrin. Platelet inhibition can be demonstrated two hours after a single dose of oral clopidogrel, but the onset of action is slow, so a loading dose of either 600 or 300 mg is administered when a rapid effect is needed.
Clopidogrel is used to prevent heart attack and stroke in people who are at high risk of these events, including those with a history of myocardial infarction and other forms of acute coronary syndrome, stroke, and those with peripheral artery disease.
Treatment with clopidogrel or a related drug is recommended by the American Heart Association and the American College of Cardiology for people who:
It is also used, along with acetylsalicylic acid (ASA, aspirin), for the prevention of thrombosis after placement of a coronary stent or as an alternative antiplatelet drug for people intolerant to aspirin.
Clopidogrel's benefit is primarily in those who smoke cigarettes (25% benefit), with only slight (8%) benefit in those who do not smoke cigarettes.
Consensus-based therapeutic guidelines also recommend the use of clopidogrel rather than ASA for antiplatelet therapy in people with a history of gastric ulceration, as inhibition of the synthesis of prostaglandins by ASA can exacerbate this condition. In people with healed ASA-induced ulcers, however, those receiving ASA plus the proton pump inhibitor esomeprazole had a lower incidence of recurrent ulcer bleeding than those receiving clopidogrel. However, prophylaxis with proton pump inhibitors along with clopidogrel following acute coronary syndrome may increase adverse cardiac outcomes, possibly due to inhibition of CYP2C19, which is required for the conversion of clopidogrel to its active form. The European Medicines Agency has issued a public statement on a possible interaction between clopidogrel and proton pump inhibitors. However, several cardiologists have voiced concern that the studies on which these warnings are based have many limitations and that it is not certain whether an interaction between clopidogrel and proton pump inhibitors is real.
Side effects associated with use of Clopidogrel, include the following:
Less common side effects of clopidogrel include:
Postmarketing side effects of clopidogrel reported include:
Acute Coronary Syndrome
Unstable angina, non-ST-segment elevation heart attack (myocardial infarction [MI]) (NSTEMI): 300 mg loading dose; initiating therapy without a loading dose will delay establishment of antiplatelet effect by several days; following the loading dose, administer 75 mg/day orally for up to 12 months; may administer beyond 12 months if used in combination with aspirin (75-100 mg/day); long-term combination therapy with aspirin, following stent placement, is individualized depending on how a patient tolerates long-term dual antiplatelet therapy (DAPT), whether they have stable coronary artery disease, and do NOT have risk factors (e.g., transient ischemic attack [TIA] or stroke, age over 75 years, bleeding risk, low body weight, concurrent medications)
ST-segment elevation myocardial infarction (MI) (STEMI): 75 mg/day orally in combination with aspirin 162-325 mg/day and then 81-162 mg/day
Age under 75 years
Age over 75 years
Recent heart attack (Myocardial Infarction [MI]), Stroke, or Established Peripheral Arterial Disease
Coronary Artery Disease
If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.
Severe interactions of clopidogrel include:
Clopidogrel has serious interactions with at least 42 different drugs.
Clopidogrel has moderate interactions with at least 141 different drugs.
Mild Interactions of clopidogrel include:
It is not known whether clopidogrel is excreted in human milk; because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from clopidogrel, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account importance of drug to mother.