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Clopidogrel

Medical and Pharmacy Editor:

Brand Name: Plavix

Generic Name: clopidogrel

Drug Class: Antiplatelet Agents, Cardiovascular; Antiplatelet Agents, Hematologic

What Is Clopidogrel and How Does It Work?

Clopidogrel is used to prevent heart attacks and strokes in persons with heart disease (recent heart attack), recent stroke, or blood circulation disease (peripheral vascular disease).

Clopidogrel is also used with aspirin to treat new/worsening chest pain (new heart attack, unstable angina) and to keep blood vessels open and prevent blood clots after certain procedures (such as cardiac stent).

Clopidogrel works by blocking platelets from sticking together and prevents them from forming harmful clots. It is an antiplatelet drug. It helps keep blood flowing smoothly in your body.

Clopidogrel is available under the following different brand names: Plavix.

Dosages of Clopidogrel:

Dosage Forms and Strengths

Tablet

  • 75 mg
  • 300 mg

Dosage Considerations – Should be Given as Follows:

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

  • 300 mg loading dose followed by 75 mg for 14 days up to 12 months (if no bleeding)
  • Concomitant therapy with aspirin: Administer in combination with aspirin 75-325 mg once/day with or without thrombolytics

Age over 75 years

  • No loading dose
  • 75 mg for 14 days up to 12 months (if no bleeding)

Recent heart attack (Myocardial Infarction [MI]), Stroke, or Established Peripheral Arterial Disease

  • 75 mg orally once/day without a loading dose; recommended as alternative to aspirin or concomitantly with aspirin if patient not at increased risk for bleeding but at high risk for cardiovascular disease

Coronary Artery Disease

  • 75 mg orally once/day

Cardioembolic Stroke

  • Prophylaxis if patient not candidate for oral anticoagulation
  • 75 mg/day orally

Dosing Modifications

  • Renal impairment: Dose adjustment not necessary
  • Hepatic impairment: Use caution; experience limited

Dosing Considerations

  • CYP2C19 poor metabolizers associated with diminished antiplatelet response to clopidogrel; although higher-dose regimen (600 mg loading dose followed by 150 mg once daily) in poor metabolizers increases antiplatelet response, no appropriate dosing regimen for poor metabolizers has been established in clinical outcome trials
  • Not recommended for pediatric use

What Are Side Effects Associated with Using Clopidogrel?

Side effects associated with use of Clopidogrel, include the following:

Less common side effects of clopidogrel include:

Postmarketing side effects of clopidogrel reported include:

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

What Other Drugs Interact with Clopidogrel ?

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:

  • ombitasvir/paritaprevir/ritonavir, and dasabuvir

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:

This information does not contain all possible interactions or adverse effects. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns or for more information about this medicine.

What Are Warnings and Precautions for Clopidogrel ?

Warnings

  • Clopidogrel's antiplatelet activity is dependent on conversion to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19
  • Tests are available to identify patients who are CYP2C19 poor metabolizers
  • Consider use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers
  • This medication contains clopidogrel. Do not take Plavix if you are allergic to clopidogrel or any ingredients contained in this drug
  • Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately

Contraindications

Effects of Drug Abuse

  • No information provided

Short-Term Effects

  • See "What Are Side Effects Associated with Using Clopidogrel?"

Long-Term Effects

  • See "What Are Side Effects Associated with Using Clopidogrel?"

Cautions

  • Use with caution in patients with bleeding or platelet disorders
  • Premature discontinuation increases risk of cardiovascular events; discontinue 5 days prior to elective surgery that has a major risk of bleeding
  • Use caution in patients with atrial fibrillation; assess bleeding risk carefully; significant increase in major bleeding events reported in patients receiving clopidogrel plus aspirin instead of aspirin alone
  • Patients allergic to aspirin who are undergoing percutaneous coronary intervention (PCI); see American Heart Association (AHA)/American College of Chest Physicians (ACCP)/American College of Cardiology (ACC) recommendations
  • Rare but potentially fatal thrombotic thrombocytopenic purpura associated with use
  • Risk of bleeding with potentially fatal outcome
  • Hepatic or renal impairment
  • Allergic cross-reactivity including rash, angioedema, or hematologic reaction among thienopyridines (e.g., ticlopidine, prasugrel) reported; evaluate patient for history of hypersensitivity
  • Use caution in patients with severe hepatic or renal impairment
  • Use caution or avoid in patients with hypersensitivity or hematologic reactions to previous thienopyridine use, including ticlopidine and prasugrel
  • Use caution in patients receiving either anticoagulants, including heparin and warfarin, or other platelet aggregation inhibitors; risk of bleeding increases
  • Premature interruption of therapy may result in stent thrombosis with subsequent fatal and nonfatal myocardial infarction; duration of therapy is determined by type of stent placed
  • May increase risk of major hemorrhage in patients with recent lacunar stroke
  • CYP2C19 inhibition and poor metabolizers:
    • Metabolism of clopidogrel to its active metabolite can be impaired by genetic variations in CYP2C19
    • Clopidogrel is a pro-drug and requires CYP2C19 to convert to active metabolite; inhibition of platelet aggregation is entirely due to active metabolite
    • CYP2C19*2 and *3 alleles have no functional metabolism of clopidogrel to active metabolite; CYP2C19*4, *5, *6, *7, and *8 may be associated with absent or reduced metabolism of clopidogrel but are less frequent than CYP2C19*2 and *3
    • More than 50% of Asians have CYP2C19 genetic variants that inhibit clopidogrel metabolism
    • Use of CYP2C19 inhibitors (e.g., proton pump inhibitors [PPIs]) or use in poor metabolizers may decrease formation of active metabolite, thereby decreasing antiplatelet effect; observational studies and 1 randomized clinical trial have shown concomitant use of clopidogrel and PPIs to have inconsistent effects on cardiovascular outcomes

Pregnancy and Lactation

  • There are no adequate and well-controlled studies of clopidogrel use in pregnant women; because animal reproduction studies are not always predictive of human response, clopidogrel should be used during pregnancy only if clearly needed
  • 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
Reviewed on 4/17/2017


SOURCE:
Medscape. Clopidogrel.
https://reference.medscape.com/drug/plavix-clopidogrel-342141
https://www.rxlist.com/plavix-side-effects-drug-center.htm

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