Dosing & Uses
Dosage Forms & Strengths
tablet
- 75mg
- 300mg
Acute Coronary Syndrome
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 >75 years, bleeding risk, low body wt, concurrent medications)
ST-segment elevation MI (STEMI): 75 mg/day PO in combination with aspirin 162-325 mg/day and then 81-162 mg/day
<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 qDay with or without thrombolytics
>75 years
- No loading dose
- 75 mg for 14 days up to 12 months (if no bleeding)
Recent MI, Stroke, or Established Peripheral Arterial Disease
75 mg PO qDay without a loading dose; recommended as alternative to aspirin or concomitantly with aspirin if patient not at increased risk for bleeding but at high risk for cardiovascular disease
Coronary Artery Disease
75 mg PO qDay
Cardioembolic Stroke
Prophylaxis if patient not candidate for oral anticoagulation
75 mg/day PO
Carotid Artery Stenting (Off-label)
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
Dosage 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 has been established in clinical outcome trials
Not recommended
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
1-10%
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%)
<1%
Severe neutropenia
Thrombotic thrombocytopenic purpura
Acute liver failure
Aplastic anemia
Hypotension
Hepatitis
Myalgia
Eczema
Erythema
Agranulocytosis
Postmarketing Reports
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
Warnings
Black Box 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 use of another platelet P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers
Contraindications
Hypersensitivity
Active pathologic bleeding (eg, peptic ulcer, intracranial hemorrhage)
Cautions
Use with caution in patients with bleeding or platelet disorders
Premature discontinuation increases risk of cardiovascular events; discontinue 5 days prior to elective surgery that has a major risk of bleeding
Use caution in patients with atrial fibrillation; assess bleeding risk carefully; significant increase in major bleeding events reported in patients receiving clopidogrel plus aspirin instead of aspirin alone
Patients allergic to aspirin who are undergoing 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 use
Risk of bleeding with potentially fatal outcome
Hepatic or renal impairment
Allergic cross-reactivity including rash, angioedema, or hematologic reaction among thienopyridines (eg, ticlopidine, prasugrel) reported; evaluate patient for 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; 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
P2Y12 inhibitors (thienopyridines), including clopidogrel, inhibit platelet aggregation for lifetime of platelet (7-10 days); because half-life of clopidogrel’s active metabolite is short, it may be possible to restore hemostasis by administering exogenous platelets; however, platelet transfusions within 4 hours of loading dose or 2 hours of the maintenance dose may be less effective
May increase risk of major hemorrhage in patients with recent lacunar stroke
CYP2C19 inhibition & poor metabolizers
- Metabolism of clopidogrel to its active metabolite can be impaired by genetic variations in CYP2C19
- Clopidogrel is a prodrug and requires CYP2C19 to convert to active metabolite; inhibition of platelet aggregation is entirely due to 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
- >50% of Asians have CYP2C19 genetic variants that inhibit clopidogrel metabolism
- Use of CYP2C19 inhibitors (eg, proton pump inhibitors [PPIs]) or use in poor metabolizers may decrease formation of 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
- Use of drugs that induce the activity of CYP2C19 would be expected to result in increased drug levels of the active metabolite of clopidogrel and might potentiate bleeding risk; as a precaution, avoid concomitant use of strong CYP2C19 inducers
Pregnancy & Lactation
Pregnancy
Available data from cases reported over two decades in published literature and postmarketing surveillance have not identified any drug-associated risks for major birth defects or miscarriage; there are risks to pregnant woman and fetus associated with myocardial infarction and stroke
Myocardial infarction and stroke are medical emergencies; therapy for pregnant woman should not be withheld because of potential concerns regarding effects of clopidogrel on the fetus
Labor or delivery
- Therapy during labor or delivery will increase risk of maternal bleeding and hemorrhage; avoid neuraxial blockade during clopidogrel use because of risk of spinal hematoma; when possible, discontinue therapy 5-7 days prior to labor, delivery, or neuraxial blockade
Animal data
- Embryo-fetal development studies performed showed no evidence of fetotoxicity when drug administered to pregnant rats and rabbits during organogenesis at doses corresponding to 65 and 78 times the recommended daily human dose
Lactation
There are no data on presence of drug in human milk or effects on milk production; no adverse effects on breastfed infants observed during lactation in a small number of postmarketing cases; studies in rats have shown that clopidogrel and/or its metabolites are present in milk; when a drug is present in animal milk, it is likely that the drug will be present in human milk; consider developmental and health benefits of breastfeeding along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibitor of adenosine diphosphate (ADP)-induced pathway for platelet aggregation
Absorption
Bioavailability: >50%
Onset: 2 hr
Peak serum time: 0.75 hr
Peak plasma concentration: 3 mg/L
Distribution
Protein bound: 98%
Metabolism
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); further activation of thiol metabolite is required through hydrolysis via paraoxonase-1 (PON-1); allele variation of PON-1 may inhibit activation and increase risk for stent thrombosis
Elimination
Half-life: 6 hr (parent drug); 30 min (active metabolite)
Excretion: Urine (50%), feces (46%)
Images
Patient Handout
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.