Clopidogrel

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 the 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 an alternative to aspirin or concomitantly with aspirin if patient not at increased risk for bleeding but high risk for cardiovascular disease

Coronary Artery Disease

• 75 mg orally once/day

Cardioembolic Stroke

• Prophylaxis if patient not a 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 have been established in clinical outcome trials
• Not recommended for pediatric use

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

• Upper respiratory tract infection
• Chest pain
• Headache
• Flulike syndrome
• Joint pain
• Pain
• Dizziness
• Diarrhea
• Rash
• Runny or stuffy nose
• Depression
• Urinary tract infection
• Increased bleeding
• Nosebleeds
• Itching
• Bruising

Less common side effects of clopidogrel include:

• Severely low white blood cell counts (neutropenia)
• Thrombotic thrombocytopenic purpura
• Acute liver failure
• Aplastic anemia
• Low blood pressure (hypotension)
• Hepatitis
• Muscle pain
• Eczema
• Skin redness
• Agranulocytosis

Postmarketing side effects of clopidogrel reported include:

• Blood and lymphatic system disorders: Agranulocytosis, aplastic anemia/pancytopenia, thrombotic thrombocytopenic purpura (TTP), acquired hemophilia A
• Eye disorders: Eye (conjunctival, ocular, retinal) bleeding
• Gastrointestinal disorders: Gastrointestinal and retroperitoneal hemorrhage with fatal outcome, colitis (including ulcerative or lymphocytic colitis), pancreatitis, stomatitis, gastric/duodenal ulcer, diarrhea
• General disorders and administration site condition: Fever, hemorrhage of operative wound
• Hepato-biliary disorders: Acute liver failure, hepatitis (non-infectious), abnormal liver function test
• Immune system disorders: Hypersensitivity reactions, anaphylactoid reactions, serum sickness
• Musculoskeletal, connective tissue and bone disorders: Musculoskeletal bleeding, muscle pain, joint pain, arthritis
• Nervous system disorders: Taste disorders, fatal intracranial bleeding, headache
• Psychiatric disorders: Confusion, hallucinations
• Respiratory, thoracic, and mediastinal disorders: Bronchospasm, interstitial pneumonitis, respiratory tract bleeding, eosinophilic pneumonia
• Renal and urinary disorders: Increased creatinine levels
• Skin and subcutaneous tissue disorders: Maculopapular, erythematous, or exfoliative rash, urticaria, bullous dermatitis, eczema, toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, drug-induced hypersensitivity syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), erythema multiforme, skin bleeding, lichen planus, generalized itching, acute generalized exanthematous pustulosis (AGEP)
• Vascular disorders: Vasculitis, hypotension

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

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:
  • aspirin rectal
  • devil's claw
  • ethotoin
  • fluvastatin
  • fosphenytoin
  • ginger
  • ginkgo biloba
  • horse chestnut seed
  • ibuprofen/famotidine
  • phenytoin
  • salicylates (non-ASA)
  • tolbutamide
  • torsemide
  • verteporfin

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.

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 the 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

• Hypersensitivity
• Active pathologic bleeding (e.g., peptic ulcer, intracranial hemorrhage)

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 the risk of cardiovascular events; discontinue 5 days before elective surgery that has a major risk of bleeding
• Use caution in patients with atrial fibrillation; assess bleeding risk carefully; a 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 the 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 the patient for a 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; the 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 the 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 the 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 the formation of the 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 the drug, taking into account importance of the drug to mother