No

Antiplatelet Agent

Reduce atherosclerotic events (myocardial infarction, stroke, vascular deaths) in patients with atherosclerosis documented by recent myocardial infarction, recent stroke, or established peripheral arterial disease; prevention of thrombotic complications after coronary stenting

B

Hypersensitivity to clopidogrel or any component; active pathological bleeding such as PUD or intracranial hemorrhage; coagulation disorders

Use with caution in patients who may be at risk of increased bleeding. Consider discontinuing 7 days before elective surgery. Use caution in mixing with other antiplatelet drugs. Use with caution in patients with severe liver disease (experience is limited). Cases of thrombotic thrombocytopenic purpura (usually occurring within the first 2 weeks of therapy) have been reported.

As with all drugs which may affect hemostasis, bleeding is associated with clopidogrel. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents which alter hemostasis and patient susceptibility.

Gastrointestinal: The overall incidence of gastrointestinal events (including abdominal pain, vomiting, dyspepsia, gastritis and constipation) has been documented to be 27.1% compared to 29.8% in patients receiving aspirin.

2.5% to 10%:

Cardiovascular: Chest pain (8.3%), edema (4.1%), hypertension (4.3%)

Central nervous system: Headache (7.6%), dizziness (6.2%), depression (3.6%), fatigue (3.3%), general pain (6.4%)

Dermatologic: Rash (4.2%), pruritus (3.3%)

Endocrine and metabolic: Hypercholesterolemia (4.0%)

Gastrointestinal: Abdominal pain (5.6%), dyspepsia (5.2%), diarrhea (4.5%), nausea (3.4%), hemorrhage (2%)

Genitourinary: Urinary tract infection (3.1%)

Hematologic: Purpura (5.3%), epistaxis (2.9%)

Hepatic: Liver function test abnormalities (<3%; discontinued in 0.11%)

Neuromuscular and skeletal: Arthralgia (6.3%), back pain (5.8%)

Respiratory: Dyspnea (4.5%), rhinitis (4.2%), bronchitis (3.7%), coughing (3.1%), upper respiratory infections (8.7%)

Miscellaneous: Flu-like syndrome (7.5%)

1% to 2.5%: Syncope, palpitation, weakness, cardiac failure, leg cramps, neuralgia, paresthesia, vertigo, atrial fibrillation, hyperuricemia, gout, arthritis, GI hemorrhage, hematoma, anxiety, insomnia, anemia, eczema, cystitis, cataract, conjunctivitis

<1% (Limited to important or life-threatening symptoms): Allergic reaction, angioedema, bronchospasm, anaphylactoid reaction, ischemic necrosis, bilirubinemia, fatty liver, hematuria, hemoptysis, intracranial hemorrhage (0.4%), retroperitoneal bleeding, hepatitis, ocular hemorrhage, pulmonary hemorrhage, purpura, thrombocytopenia, aplastic anemia, hypochromic anemia, menorrhagia, hemothorax, bullous eruption, maculopapular rash, urticaria, agranulocytosis, granulocytopenia, leukopenia, neutropenia (0.05%), thrombotic thrombocytopenic purpura

Symptoms of acute toxicity include vomiting, prostration, difficulty breathing, and gastrointestinal hemorrhage. Only one case of overdose with clopidogrel has been reported to date, no symptoms were reported with this case and no specific treatments were required.

Based on its pharmacology, platelet transfusions may be an appropriate treatment when attempting to reverse the effects of clopidogrel. After decontamination, treatment is symptomatic and supportive.

CYP2C9 inhibitor

Anticoagulants or other antiplatelet agents may increase the risk of bleeding.

Warfarin metabolism may be decreased due to clopidogrel inhibition of CYP2C9. Hypoprothrombinemic effects may be increased; monitor INR carefully during initiation or withdrawal.

Blocks the ADP receptors, which prevent fibrinogen binding at that site and thereby reduce the possibility of platelet adhesion and aggregation

Onset:

Maximal effect on bleeding time: 5-6 days

Maximal effect on platelet function: 3-7 days

Metabolism: Hydrolysis in the liver; biotransformation of clopidogrel is needed to produce inhibition of platelet aggregation, but an active metabolite responsible for the activity of the drug has not yet been isolated

Half-life, elimination: ~8 hours

Time to peak serum concentration: Oral: ~1 hour

Elimination: Excretion via the kidneys

Adults: Oral: 75 mg once daily

Food: May be taken without regard to meals

Signs of bleeding

Clopidogrel may be considered in aspirin-intolerant patients. It has not been as extensively studied as aspirin or even ticlopidine when used in patients with coronary artery disease. When used instead of aspirin, cost may become an issue. In one study (CAPRIE), small but significantly superior effects of clopidogrel versus aspirin occurred in patients at risk for ischemic events. For the prevention of thrombotic complications, clopidogrel is similar in efficacy to ticlopidine and is not associated with neutropenia.

None reported

Rarely may produce neutropenia; use caution with clozapine and carbamazepine

No information available to require special precautions

If a patient is to undergo elective surgery and an antiplatelet effect is not desired, clopidogrel should be discontinued 7 days prior to surgery

Take as directed. May cause headache or dizziness; use caution when driving or engaging in tasks that require alertness until response to drug is known. Small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may reduce nausea or vomiting. Mild analgesics may reduce arthralgia or back pain. Report immediately unusual or acute chest pain or respiratory difficulties, skin rash, unresolved diarrhea or gastrointestinal distress, nosebleed, or acute headache. Breast-feeding precautions: Breast-feeding is not recommended.

Tablet, as bisulfate: 75 mg

Boneu B and Destelle G, "Platelet Antiaggregating Activity and Tolerance of Clopidogrel in Atherosclerotic Patients," Thromb Haemost, 1996, 76(6):939-43.

CAPRIE Steering Committee, "A Randomized, Blinded Trial of Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE)," Lancet, 1996, 348:1329-39.

Coukell AJ and Markham A, "Clopidogrel," Drugs, 1997, 54(5):745-51.