Plavix
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clopidogrel bisulfate
Pharmacologic class: Platelet aggregation inhibitor
Therapeutic class: Antiplatelet drug
Pregnancy risk category B
FDA Box Warning
• Effectiveness of clopidogrel depends on activation to an active metabolite by the cytochrome P(CYP) 450 system, principally CYP2C19.
• Patients identified as CYP2C19 poor metabolizers treated with clopidogrel at recommended dosages exhibit higher cardiovascular event rates following acute coronary syndrome or percutaneous coronary intervention than patients with normal CYP2C19 function.
• Tests are available to identify a patient's CYP2C19 genotype and can be used as an aid in determining therapeutic strategy.
• Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolizers.
Action
Inhibits platelet aggregation by blocking binding of adenosine diphosphate to platelets, thereby preventing thrombus formation
Availability
Tablets: 75 mg, 300 mg
Indications and dosages
➣ Recent myocardial infarction (MI) or stroke or established peripheral arterial disease
Adults: 75 mg/day P.O.
➣ Acute coronary syndrome (ACS)
Adults: 300 mg P.O. as a loading dose, then 75 mg/day P.O. in combination with aspirin (75 to 325 mg once daily) for patients with non-ST-segment elevation ACS (unstable angina, non-ST-elevation MI)
Adults: 75 mg P.O. once daily in combination with aspirin (75 to 325 mg once daily), with or without a loading dose and with or without thrombolytics for patients with ST-elevation MI
Contraindications
• Hypersensitivity to drug
• Active pathologic bleeding
Precautions
Use cautiously in:
• thrombotic thrombocytopenic purpura
• increased risk of bleeding
• concomitant use of drugs that inhibit CYP2C19 (such as esomeprazole, omeprazole)
• concomitant use of aspirin in patients with recent transient ischemic attack or cerebrovascular accident
• premature discontinuation of drug
• pregnant or breastfeeding patients
• children (safety and efficacy not established).
Administration
• Give with or without food.
• Know that drug may need to be discontinued 5 days before surgery.

Adverse reactions
CNS: depression, dizziness, fatigue, headache
CV: chest pain, hypertension
EENT: epistaxis, rhinitis
GI: diarrhea, abdominal pain, dyspepsia, gastritis, GI bleeding
Hematologic: bleeding, neutropenia, thrombotic thrombocytopenic purpura
Metabolic: hypercholesterolemia, gout
Musculoskeletal: joint pain, back pain
Respiratory: cough, dyspnea, bronchitis, upper respiratory tract infection, bronchospasm
Skin: pruritus, rash, angioedema
Other: hypersensitivity reactions, anaphylactic reactions
Interactions
Drug-drug. Abciximab, aspirin, eptifibatide, heparin, heparinoids, nonsteroidal anti-inflammatory drugs (NSAIDs), thrombolytics, ticlopidine, tirofiban, warfarin: increased risk of bleeding
CYP2C19 inhibitors (such as esomeprazole, omeprazole): significantly reduced clopidogrel antiplatelet activity
Fluvastatin, many NSAIDs, phenytoin, tamoxifen, tolbutamide, torsemide: interference with metabolism of these drugs
Drug-diagnostic tests. Bilirubin, hepatic enzymes, nonprotein nitrogen, total cholesterol, uric acid: increased levels
Platelets: decreased count
Drug-herbs. Anise, arnica, chamomile, clove, fenugreek, feverfew, garlic, ginger, ginkgo, ginseng: increased risk of bleeding
Patient monitoring
• Monitor hemoglobin and hematocrit periodically.
• Monitor patient for unusual bleeding or bruising; drug significantly increases risk of bleeding.
• Assess for occult GI blood loss if patient is receiving naproxen concurrently with clopidogrel.
Patient teaching
• Tell patient to take tablets with or without food.
☞ Advise patient to immediately report unusual or acute chest pain, respiratory difficulty, rash, purplish bruises on skin or in mouth, purple skin patches, unusual fatigue, fast heart rate, confusion, signs and symptoms of stroke (including weakness on one side, speech changes), low urine output, unresolved bleeding, diarrhea, GI distress, nosebleed, or acute headache.
☞ Instruct patient not to discontinue drug without consulting prescriber.
• Instruct patient to tell all health care providers that he's taking clopidogrel, especially if surgery is scheduled or new drugs are prescribed.
• Advise patient to contact prescriber before taking over-the-counter products, particularly nonsteroidal anti-inflammatory drugs.
• Tell patient drug may cause headache and dizziness. Caution him to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Advise patient to minimize adverse GI effects by eating small, frequent meals or chewing gum.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.