SIDE EFFECTS CNS: Headache, dizziness, depression CV: Edema, hypertension, chest pain GI: Diarrhea, constipation, GI discomfort HEMA: Bleedi

clopidogrel (Rx) Plavix Func. class.: Platelet aggregation inhibitor Chem. class.: Thienopyridine derivative Do not confuse: Plavix/Paxil

SIDE EFFECTS CNS: Headache, dizziness, depression CV: Edema, hypertension, chest pain GI: Diarrhea, constipation, GI discomfort HEMA: Bleeding (major/minor from any site), neutropenia, aplastic anemia, agranulocytosis, thrombotic thrombocytopenic purpura INTEG: Rash, pruritus, anaphylaxis MISC: Fatigue, intracranial hemorrhage, toxic epidermal necrolysis, Stevens-Johnson syndrome, flulike syndrome MS: Arthralgia RESP: Bronchospasm PHARMACOKINETICS Rapidly absorbed; metabolized by liver (CYP3A4, CYP2B6, CYP1A2, CYP2C8); excreted in urine, feces; half-life 6 hr.; protein binding 95%; effect on platelets after 3-7 days

DOSAGE AND ROUTES Recent MI, stroke, peripheral arterial disease, TIA • Adult: PO 75 mg/day with/without aspirin Acute MI (ST-segment elevation, MI) • Adult: PO 75 mg/day with aspirin 75-325 mg/day; with or without loading dose or thrombolytics; those >75 yr no loading dose should be given; continue this product for 2 wk to <1 yr with aspirin 81 mg indefinitely Acute coronary syndrome • Adult: PO loading dose 300 mg, then 75 mg/day with aspirin Available forms: Tablets 75, 300 mg Administer: • Without regard to food • Should be discontinued 5 days prior to elective surgery if an antiplatelet action is not desired

ACTION: Inhibits ADP-induced platelet aggregation USES: Reducing the risk of stroke, MI, vascular death, peripheral arterial disease in high-risk patients, acute coronary syndrome, transient ischemic attack (TIA), unstable angina CONTRAINDICATIONS Hypersensitivity, active bleeding Precautions: Pregnancy, breastfeeding, children, previous hepatic disease, increased bleeding risk, neutropenia, agranulocytosis, renal disease, Asian/Black/Caucasian patients Black Box Warning: CYP2C19 allele (poor metabolizers)

NURSING CONSIDERATIONS Assess: • Thrombotic/thrombolytic purpura: fever, thrombocytopenia, hemolytic anemia, neurologic changes, treat immediately Black Box Warning: CYP2C19 allele (poor metabolizers): consider using another antiplatelet product; higher CV reaction occurs after acute coronary syndrome or PCI; tests are available to determine CYP2C19 allele • Hepatic studies: AST, ALT, bilirubin, creatinine (long-term therapy) • Blood studies: CBC, differential, Hct, HB, PT, cholesterol (long-term therapy); thrombocytopenia, neutropenia are rare • Hypersensitivity: rash, angioedema may occur Evaluate: • Therapeutic response: absence of stroke, MI Teach patient/family: • That blood work will be necessary during treatment (CBC, LFTs) • To report any unusual bruising, bleeding to prescriber; that it may take longer to stop bleeding • To take without regard to food • To tell all health care providers that clopidogrel is being used; may be held for 5 days before surgery, restart as soon as possible • Hypersensitivity: To report immediately rash, pruritus • Pregnancy/breastfeeding: to notify provider if pregnancy is planned or suspected or if breastfeeding; do not breastfeed, use cautiously in pregnancy

INTERACTIONSBlack Box Warning: Avoid use with CYP2C19 inhibitors (omeprazole, esomeprazole) CYP2C8 substrates (repaglinide): Increased level of CYP2C8 substrates, avoid using together Increase: bleeding risk—anticoagulants, aspirin, NSAIDs, abciximab, eptifibatide, tirofiban, thrombolytics, ticlopidine, SSRIs, Treprostinil, rifampin, SNRIs, prasugrel, monitor closely Increase: action of some NSAIDs, phenytoin, Tolbutamide, tamoxifen, torsemide, fluvastatin, warfarin, monitor closely Decrease: clopidogrel effect—proton pump inhibitors (PPIs) Decrease: CYP3A4 inhibitors/substrates— atorvastatin, simvastatin, cerivastatin Drug/Food Grapefruit juice: may decrease antiplatelet effect Drug/Herb Increase: clopidogrel effect—feverfew, fish oil, omega-3 fatty acid, garlic, ginger, ginkgo biloba, green tea, horse chestnut Decrease: clopidogrel effect—bilberry, saw palmetto Drug/Lab Test Increase: AST, ALT, bilirubin, uric acid, total cholesterol, nonprotein nitrogen (NPN)

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