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Unstable angina, non-ST-segment elevation 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 PO 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 (eg, TIA or stroke, age 300 mg PO plus aspirin 81-325 mg for 1 dose on day before carotid artery stenting (CAS), then 75 mg/day PO plus aspirin 81-325 mg/day for at least 30 days after CAS Alternative: 300-600 mg PO once, then 75 mg/day for 4 days before CAS in combination with aspirin 81-325 mg/day CYP2C19 poor metabolizers associated with diminished antiplatelet response to clopidogrel; although hher-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 Upper respiratory tract infection (8.7%) Chest pain (8.3%) Headache (7.6%) Flulike syndrome (7.5%) Arthralgia (6%) Pain (6%) Dizziness (6%) Diarrhea (4.5%) Rash (4.2%) Rhinitis (4.2%) Depression (3.6%) Urinary tract infection (3.1%) 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, myalgia, arthralgia, 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 pruritus, acute generalized exanthematous pustulosis (AGEP) Vascular disorders: Vasculitis, hypotension 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 Use with caution in patients with bleeding or platelet disorders Premature discontinuation increases risk of cardiovascular events; 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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 Pregnancy: There are no adequate and well-controlled studies in pregnant women; because animal reproduction studies are not always predictive of human response, clopidogrel should be used during pregnancy only if clearly needed Lactation: Not known whether drug is excreted in human milk; because many drugs are excreted in human milk and because of 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 Metabolized in liver by hepatic CYP450 enzymes (in vitro by CYP3A4, CYP2C19 [predominantly], others) to generate active metabolite and also by esterase to generate inactive metabolite Metabolites: Thiol (active); 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