Bedside Snapshot
- Use It For
- STEMI with fibrinolysis; ACS when ticagrelor or prasugrel is not an option, or with an oral anticoagulant; minor stroke or high-risk TIA (with aspirin); long-term monotherapy after MI or stroke, or in PAD
- Adult Dose
- ACS: 300–600 mg PO load before PCI, then 75 mg daily (600 mg exceeds FDA label 300 mg)
- Fibrinolysis: 300 mg load if ≤75 yr; 75 mg, no load, if >75 yr
- Minor stroke/TIA: 300 mg load, then 75 mg daily with aspirin for 21 days
- Pediatric Dose
- Not established in children: specialist/medical-control use only. Infants ≤24 months: 0.2 mg/kg PO once daily (specialist use); never exceed the adult 75 mg/day
- Onset / Duration
- PO: effect from about 2 hr; full by about 2 hr after 600 mg in stable patients (later with opioids or after cardiac arrest), slower after 300 mg; no load: steady state day 3–7 / recovers about 5 days after stopping
- Do Not Give / Hold If
- Active pathological bleeding (peptic ulcer, intracranial hemorrhage); clopidogrel hypersensitivity; hold 5 days before major-bleeding-risk surgery, 5–7 days before neuraxial block
- Watch For
- Bleeding (melena, falling Hgb, hematuria); intracranial hemorrhage (headache, new deficit); TTP (low platelets, schistocytes, confusion, renal injury), even after <2 weeks
- Reversal / Rescue
- No reversal agent: hold, control the source; platelets for life-threatening bleeding or emergency surgery (less effective within 4 hr of a load); not routinely in nonsurgical ICH
- Must Remember
- Never stop it without a plan after a stent: early discontinuation raises the risk of MI and stent thrombosis. Holds for bleeding or surgery need cardiology input and a restart plan
Indications
Emergency & Prehospital
- STEMI treated with fibrinolysis: the P2Y12 inhibitor to give alongside aspirin and the fibrinolytic. It is the only P2Y12 inhibitor with a Class 1 recommendation in this setting
- NSTE-ACS and STEMI going to PCI: the second-line choice when ticagrelor or prasugrel is unavailable, contraindicated or not tolerated. Ticagrelor or prasugrel is still the first pick
ED / ICU / Transport
- NSTE-ACS without planned invasive care: the fallback when ticagrelor (preferred) is unavailable or not tolerated
- ACS or PCI in a patient who needs an oral anticoagulant (e.g. atrial fibrillation): pair it with the anticoagulant. It is the preferred P2Y12 inhibitor here
- De-escalation after ACS-PCI: after 1 month, switch from ticagrelor or prasugrel to clopidogrel. The goal is less bleeding
- Minor ischemic stroke or high-risk TIA: short-course dual antiplatelet therapy (DAPT) with aspirin. The combination is off-label, though guidelines recommend it
- Who may give it: an oral antiplatelet ordered by a prescriber. An RN gives it in the ED, ICU or cath lab, and transport continues it on the sending order. Prehospital use varies by state, agency and facility protocol.
Other Uses
- Recent MI, recent stroke or established peripheral artery disease (PAD): long-term monotherapy to cut MI and stroke risk. It is also the usual alternative when aspirin is not tolerated or the patient is allergic to it
- PAD after endovascular revascularization: DAPT with low-dose aspirin
- Elective PCI for chronic coronary disease: P2Y12 component of DAPT (off-label)
Dosing & Administration
Doses vary by protocol; follow local protocols and medical direction.
Available Forms
- Tablets: 75 mg (pink, round) and 300 mg (pink, oblong), film-coated; generic and Plavix
Adult Dosing
| Indication | Dose & Route | Repeat / Max | Notes |
|---|---|---|---|
| NSTE-ACS (PCI or medical management) | 300–600 mg PO load before PCI, then 75 mg PO daily with low-dose aspirin | Load once; maintenance max 75 mg/day | The 600 mg end of the range differs from the FDA label dose of 300 mg PO load. The load is set by cath lab protocol. Second-line: with PCI, ticagrelor or prasugrel is preferred; with medical management, ticagrelor is preferred (no prasugrel before the coronary anatomy is known). Upstream load may be considered if angiography is >24 hr away |
| STEMI with primary PCI | 600 mg PO load, then 75 mg PO daily with low-dose aspirin | Load once; maintenance max 75 mg/day | Only when prasugrel or ticagrelor is unavailable or contraindicated |
| STEMI with fibrinolysis, age ≤75 yr | 300 mg PO load with the fibrinolytic, then 75 mg PO daily | Load once; maintenance max 75 mg/day | Give with aspirin and a parenteral anticoagulant. Continue DAPT for the ACS default duration (see Dosing Notes) |
| STEMI with fibrinolysis, age >75 yr | 75 mg PO, no loading dose, then 75 mg PO daily | No load; max 75 mg/day | Guideline regimen for older patients. Continue DAPT for the ACS default duration (see Dosing Notes) |
| PCI after fibrinolysis (STEMI) | Loaded with the fibrinolytic: continue 75 mg PO daily, no repeat load. Not loaded: 300 mg PO before PCI if within 24 hr of the fibrinolytic; 600 mg PO if more than 24 hr | Load once; maintenance max 75 mg/day | Protocol-dependent: load per cath lab and cardiology; use 600 mg with caution at age 75 or older. Alternatives to support PCI: ticagrelor (age under 75, within 24 hr of the fibrinolytic) or prasugrel (more than 24 hr after) |
| Minor stroke (NIHSS ≤3) or high-risk TIA (ABCD² ≥4), within 24 hr | 300 mg PO load with aspirin, then 75 mg PO daily with aspirin for 21 days | Then single antiplatelet therapy; DAPT beyond 90 days adds bleeding without benefit | Patients not given IV thrombolysis. Known CYP2C19 loss-of-function carrier: ticagrelor-aspirin is an option |
| Minor stroke (NIHSS ≤5) or high-risk TIA (ABCD² ≥4) of presumed atherosclerotic cause, 24–72 hr; or NIHSS 4–5 within 24 hr | 300 mg PO load with aspirin, then 75 mg PO daily with aspirin for 21 days | Then single antiplatelet therapy | Patients not given IV thrombolysis. Atherosclerotic cause: a relevant ≥50% stenosis or new infarcts of presumed large-artery origin. 2026 AHA/ASA extension; a weaker recommendation than DAPT started within 24 hr |
| Elective PCI for chronic coronary disease (off-label) | 600 mg PO load if not already taking clopidogrel, then 75 mg PO daily with low-dose aspirin | Load once; maintenance max 75 mg/day | DAPT usually 6 months, then single antiplatelet therapy; shorter DAPT for selected patients per cardiology |
| Recent MI, recent stroke or established PAD | 75 mg PO daily, no loading dose | Max 75 mg/day | Monotherapy, including when aspirin is not tolerated; for symptomatic PAD, clopidogrel alone or aspirin alone is recommended |
| PAD after endovascular revascularization | 75 mg PO daily with low-dose aspirin | Max 75 mg/day; DAPT for at least 1–6 months | Then single antiplatelet therapy per vascular team |
| ACS or PCI on an oral anticoagulant | If not already taking clopidogrel, load as for ACS or PCI above (300–600 mg PO), then 75 mg PO daily with the oral anticoagulant | Load once; maintenance max 75 mg/day | Clopidogrel is the preferred P2Y12 inhibitor; aspirin is usually stopped after 1–4 weeks |
| De-escalation from ticagrelor or prasugrel | From ticagrelor: 600 mg PO load 24 hr after the last ticagrelor dose, then 75 mg PO daily. From prasugrel (after the first 30 days): 75 mg PO daily, starting 24 hr after the last dose | Load once; maintenance max 75 mg/day | After 1 month of DAPT to reduce bleeding (weaker recommendation). With bleeding concerns, 75 mg without a load may be used. Switch plan per cardiology |
Pediatric Dosing
Not established in children: Safety and effectiveness are unproven in children. Specialist use only, under pediatric cardiology or hematology direction. See weight-based dosing.
| Indication | Dose (per kg) & Route | Max Single / Max Total | Notes |
|---|---|---|---|
| Thromboprophylaxis, infants ≤24 months with cardiac disease (specialist use) | 0.2 mg/kg PO once daily | No established max; never exceed the adult 75 mg/day | Dose from infant platelet-inhibition data (PICOLO); CLARINET showed no clinical benefit in shunted infants |
| Children older than 24 months | Not established in children | Adult maximum 75 mg/day | Cardiology or hematology consult; no validated weight-based dose |
Preparation & Administration
- Food: it can be given with or without food
- Loading: you need a load when you want an effect within hours. Without one, full effect takes several days
- Opioids: morphine and other opioids slow and cut absorption of the load
- Enteral tube: tablets may be crushed and given via NG/OG tube. In healthy volunteers, crushed tablets were absorbed faster than whole ones. After cardiac arrest, absorption is impaired (see below)
- After cardiac arrest: in ventilated patients on targeted temperature management, a crushed load via NG tube was absorbed late or not at all. Most did not reach adequate platelet inhibition at 24 hr. Discuss a parenteral P2Y12 inhibitor (cangrelor) with cardiology
Dosing Notes:
- DAPT after ACS: by default, at least 12 months, provided bleeding risk is not high
- Want less bleeding after ACS-PCI? Ticagrelor monotherapy from 1 month on ticagrelor-based DAPT is recommended (Class 1). Selected patients, such as those at high bleeding risk, can reasonably take 1–3 months of DAPT, then P2Y12 inhibitor monotherapy. Clopidogrel de-escalation is the weaker option. Cardiology picks the agent and timing
- Elective surgery with major bleeding risk: stop 5 days before. Restart once hemostasis is secure
- Renal and hepatic notes: see Special Populations
Contraindications & Precautions
Contraindications
- Active pathological bleeding, such as peptic ulcer or intracranial hemorrhage
- Hypersensitivity (e.g. anaphylaxis) to clopidogrel or any tablet component
Precautions
- Omeprazole or esomeprazole: avoid them. Both significantly reduce antiplatelet effect
- Surgery: stop 5 days before surgery with major bleeding risk when possible; restart once hemostasis allows
- Labor, delivery and neuraxial anesthesia: spinal hematoma is the risk. Stop 5–7 days before when possible
- Prior reaction to another thienopyridine: rash, angioedema or hematologic reactions to another thienopyridine can cross-react here
- High bleeding risk: prior intracranial hemorrhage, recent GI bleeding, anticoagulant use
Hold / Reassess If
- Active bleeding, falling Hgb or hypotension: hold, control the source, notify the prescriber and cardiology
- New neurologic deficit or sudden severe headache: hold and obtain emergent head CT
- Falling platelets with anemia, confusion or renal injury: stop and evaluate for thrombotic thrombocytopenic purpura (TTP)
FDA Boxed Warning: The effect depends on CYP2C19 activation. Two loss-of-function alleles make a poor metabolizer, and those patients get less platelet inhibition. Tests can identify them. Consider another P2Y12 inhibitor.
Never Stop Without a Plan: Stopping early raises the risk of MI and stent thrombosis. The risk is highest soon after a stent. Involve cardiology before any hold.
Adverse Effects & Toxicity
Common
- Minor bleeding: bruising, epistaxis, hematoma, hematuria (5.1% with aspirin vs 2.4% on aspirin alone)
- Major bleeding with aspirin: 3.7% vs 2.7% on aspirin alone, mostly GI and puncture sites
- Pruritus, rash, diarrhea
Serious / Life-Threatening
| Effect | Recognition | Management |
|---|---|---|
| Major bleeding | GI bleeding (melena, hematemesis), puncture-site or retroperitoneal bleeding, falling Hgb, hypotension | Hold; source control; transfuse; see Bleeding Management |
| Intracranial hemorrhage | Headache, vomiting, new deficit, falling GCS | Hold; emergent CT; neurosurgery; see Bleeding Management |
| TTP (rare, can be fatal) | Low platelets, schistocytes on smear, neuro changes, renal injury, fever; can follow <2 weeks of use | Stop; urgent hematology; plasma exchange |
| Severe hypersensitivity | Angioedema, anaphylactoid reaction, Stevens-Johnson syndrome, DRESS, bullous rash | Stop; treat the reaction; avoid other thienopyridines |
| Hematologic and immune effects | Agranulocytosis, aplastic anemia, acquired hemophilia A (isolated prolonged aPTT with bleeding), insulin autoimmune hypoglycemia | Stop; CBC, aPTT, glucose; specialist referral |
Bleeding Management
- First steps: hold clopidogrel; local, endoscopic or surgical control; red cells as needed; call cardiology if a stent is recent
- Platelet transfusion: consider it for life-threatening bleeding or emergency surgery. It may work less well within 4 hr of a load or 2 hr of a maintenance dose. An in vitro study in volunteers taking aspirin or clopidogrel estimated 2–3 adult doses to restore platelet function. That estimate came from the aspirin results. Clinical outcome data are limited (PATCH gave clopidogrel users 2 adult doses). Dose per blood bank protocol
- Spontaneous ICH, no surgery planned: do not transfuse platelets routinely. In the PATCH trial, mostly aspirin users with some on clopidogrel, platelets made death or dependence worse. The 2022 AHA/ASA guideline calls platelet transfusion potentially harmful in aspirin-associated ICH without emergency surgery. Clopidogrel data are limited. Follow neurocritical care or blood bank protocol
- ICH needing emergency neurosurgery: platelet transfusion may be considered. The evidence comes mainly from aspirin users
- Desmopressin (DDAVP): effectiveness is uncertain. Some protocols give 0.3–0.4 mcg/kg IV once. Check sodium afterward for hyponatremia
- Tranexamic acid: it does not reverse platelet inhibition. Use it for its usual indications
Overdose & Toxicity Management
- Signs: bleeding from irreversible platelet inhibition
- Management: no antidote. Supportive care and bleeding control as above. Platelet transfusion may restore clotting
Monitoring
| Parameter | When / How Often | Target / Act If |
|---|---|---|
| Clinical: bleeding | Every assessment; after procedures and sheath removal | New bleeding, falling BP or rising HR: hold, notify, STAT CBC |
| Clinical: neuro checks | Every assessment; after falls or head injury | New deficit or severe headache: hold, emergent head CT |
| Laboratory: Hgb and platelets | Baseline; with bleeding or bruising; if TTP suspected (CBC) | |
| Laboratory: glucose | Unexplained or recurrent hypoglycemia | Consider insulin autoimmune syndrome; stop and refer |
| Laboratory: CYP2C19 genotype | When ordered or already on file | Intermediate or poor metabolizer after ACS or PCI: switch to prasugrel or ticagrelor if no contraindication |
| Medication review | Admission, handoff, every new order | Omeprazole or esomeprazole: change to pantoprazole; review anticoagulants, NSAIDs, opioids |
| Procedure timing | Before surgery, neuraxial block or invasive procedures | Record last dose: hold 5 days for major-bleeding-risk surgery and 5–7 days for neuraxial block when possible |
Interactions & Compatibility
Clinically Significant Interactions
| Drug / Class | Effect | What To Do |
|---|---|---|
| Omeprazole, esomeprazole and other CYP2C19 inhibitors | Less active metabolite and platelet inhibition; with omeprazole the effect persists even when doses are 12 hr apart | Avoid omeprazole and esomeprazole; if a PPI is needed, pantoprazole, lansoprazole or dexlansoprazole affect it less. Review other CYP2C19 inhibitors with a pharmacist |
| Opioids (morphine, fentanyl) | Delay and reduce absorption (5 mg IV morphine cut metabolite exposure 34%) | In ACS needing opioids, consider a parenteral antiplatelet agent; give the load early |
| Anticoagulants (heparin, enoxaparin, DOACs, warfarin) and fibrinolytics | Additive bleeding | Expected in ACS and PCI; keep triple therapy as short as possible |
| Aspirin, other antiplatelets, NSAIDs, SSRIs, SNRIs | Additive bleeding | Avoid chronic NSAIDs; evaluate any blood loss promptly |
| Strong CYP2C19 inducers (rifampin) | More active metabolite and platelet inhibition; bleeding | Avoid the combination |
| Repaglinide and other drugs cleared mainly by CYP2C8 | Repaglinide exposure up 3.9–5.1-fold (hypoglycemia); exposure to other CYP2C8 substrates can rise | Avoid repaglinide; if unavoidable, 0.5 mg before meals (max 4 mg/day) with closer glucose checks. Other CYP2C8 substrates: adjust dose and monitor |
| Cangrelor (IV P2Y12 inhibitor) | Clopidogrel given during the infusion has no antiplatelet effect until the next dose | Give clopidogrel 600 mg immediately after the cangrelor infusion stops |
It is an oral tablet only. No IV compatibility issues need checking.
Special Populations
- Pediatrics: not established. Specialist use only. See the Pediatric Dosing table.
- Neonates: CLARINET enrolled neonates and infants with systemic-to-pulmonary shunts. It found no benefit. Specialist use only.
- Pregnancy: Published cases and postmarketing data have not found a drug-linked risk of major birth defects or miscarriage. Don't withhold it for MI or stroke. It raises bleeding at delivery. Stop 5–7 days before labor, delivery or neuraxial block when possible.
- Lactation: human milk data are missing. No adverse effects were reported in a small number of breastfed infants. Weigh the benefits of breastfeeding against the mother's need.
- Older Adults: no dose adjustment. Bleeding still rises with age. With fibrinolysis in patients older than 75 yr, give no loading dose.
- Renal Impairment: no specific adjustment is established. Experience in moderate and severe impairment is limited. Platelet inhibition was lower in studies.
- Hepatic Impairment: no dose adjustment. Severe disease raises bleeding risk.
- Obesity / Dosing Weight: fixed dose. No weight-based adjustment is established.
- CYP2C19 Poor Metabolizers: about 2% of White, 4% of Black and 14% of Chinese patients. After ACS or PCI, prefer prasugrel or ticagrelor.
Clinical Pearls
Exam Discriminator, Which P2Y12 Inhibitor:
- For STEMI on fibrinolysis: clopidogrel
- ACS going to PCI: ticagrelor or prasugrel. Clopidogrel only as the fallback
- Prior stroke or TIA: never prasugrel
- On an oral anticoagulant too: clopidogrel
- IV P2Y12 inhibition needed in the cath lab: cangrelor
The PPI Swap: New omeprazole or esomeprazole on a patient taking clopidogrel? Antiplatelet effect is slipping away. Ask for pantoprazole instead. Spacing the doses apart does not fix it.
GP IIb/IIIa Inhibitors: Giving them upstream before PCI as routine adds bleeding without ischemic benefit. Their job is add-on bailout during PCI. No-reflow is one example.
Handoff Essentials: Hand over the indication, the stent date, the loading dose and time, and the planned DAPT duration. This gets lost easily between ED, ICU and floor.
Low Platelets Plus Confusion: Thrombocytopenia with anemia, neuro changes or renal injury, new on clopidogrel? That is TTP until proven otherwise. Check the smear for schistocytes. Call hematology for plasma exchange.
Pharmacology
Mechanism of Action
- Prodrug: hepatic CYP enzymes, mainly CYP2C19, make a short-lived active thiol metabolite. Esterases make an inactive carboxylic acid, about 85% of circulating metabolites
- The active metabolite irreversibly blocks the platelet P2Y12 ADP receptor. With no ADP signal, GP IIb/IIIa does not activate, so platelets aggregate less
- The binding is irreversible. Each exposed platelet stays inhibited for its 7–10 day lifespan. Function returns only as new platelets are made
Pharmacokinetics
| Route | Onset | Peak | Duration |
|---|---|---|---|
| PO, loading dose | First effect about 2 hr; full effect by about 2 hr after 600 mg in stable patients, later with opioids or after cardiac arrest; slower and weaker after 300 mg | Active metabolite peaks 30–60 min after a dose | Platelets inhibited for their lifespan (7–10 days) |
| PO, 75 mg daily without load | Partial inhibition on day 1 | Steady state day 3–7 (40–60% inhibition) | Function near baseline about 5 days after stopping |
- Half-life: parent drug about 6 hr; active metabolite about 30 min
- Metabolism: esterases take the inactive pathway. CYP2C19 and other CYP enzymes take the active one. The glucuronide metabolite strongly inhibits CYP2C8
- Elimination: about 50% in urine and 46% in feces over 5 days
- Absorption: at least 50%. Food does not change overall exposure
Names & Classification
- Generic Name
- Clopidogrel bisulfate
- Brand Names
- Plavix (US); multiple generics
- Pharmacologic Class
- Thienopyridine P2Y12 ADP-receptor inhibitor (irreversible, prodrug)
- Therapeutic Class
- Oral antiplatelet agent
- Controlled Substance
- Not controlled
- ISMP High-Alert
- No
- Look-Alike / Sound-Alike
- Plavix / Paxil (paroxetine); Plavix / Pradaxa (dabigatran)
References
- Sanofi-Aventis U.S. LLC. (2025). Plavix (clopidogrel tablets): Prescribing information. DailyMed, U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=de8b0b67-eb25-4684-83b5-7ad785314227
- Rao, S. V., O'Donoghue, M. L., Ruel, M., et al. (2025). 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes. Circulation, 151(13), e771–e862. https://doi.org/10.1161/CIR.0000000000001309
- Prabhakaran, S., Gonzalez, N. R., Zachrison, K. S., et al. (2026). 2026 guideline for the early management of patients with acute ischemic stroke: A guideline from the American Heart Association/American Stroke Association. Stroke, 57(8), e316–e436. https://doi.org/10.1161/STR.0000000000000513
- Greenberg, S. M., Ziai, W. C., Cordonnier, C., et al. (2022). 2022 guideline for the management of patients with spontaneous intracerebral hemorrhage: A guideline from the American Heart Association/American Stroke Association. Stroke, 53(7), e282–e361. https://doi.org/10.1161/STR.0000000000000407
- Gornik, H. L., Aronow, H. D., Goodney, P. P., et al. (2024). 2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS guideline for the management of lower extremity peripheral artery disease. Circulation, 149(24), e1313–e1410. https://doi.org/10.1161/CIR.0000000000001251
- Lee, C. R., Luzum, J. A., Sangkuhl, K., et al. (2022). Clinical Pharmacogenetics Implementation Consortium guideline for CYP2C19 genotype and clopidogrel therapy: 2022 update. Clinical Pharmacology & Therapeutics, 112(5), 959–967. https://doi.org/10.1002/cpt.2526
- Maynard, S., Bye, A. P., & Desborough, M. J. R. (2026). Can drug-induced platelet dysfunction be reversed? Research and Practice in Thrombosis and Haemostasis, 10, e103286. https://doi.org/10.1016/j.rpth.2025.103286
- Li, J. S., Yow, E., Berezny, K. Y., et al. (2008). Dosing of clopidogrel for platelet inhibition in infants and young children: Primary results of the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial (landmark trial). Circulation, 117(4), 553–559. https://doi.org/10.1161/CIRCULATIONAHA.107.715821
- Angiolillo, D. J., Rollini, F., Storey, R. F., et al. (2017). International expert consensus on switching platelet P2Y12 receptor-inhibiting therapies. Circulation, 136(20), 1955–1975. https://doi.org/10.1161/CIRCULATIONAHA.117.031164
- Hochholzer, W., Trenk, D., Frundi, D., et al. (2005). Time dependence of platelet inhibition after a 600-mg loading dose of clopidogrel in a large, unselected cohort of candidates for percutaneous coronary intervention. Circulation, 111(20), 2560–2564. https://doi.org/10.1161/01.CIR.0000160869.75810.98
- Součková, L., Opatřilová, R., Suk, P., et al. (2013). Impaired bioavailability and antiplatelet effect of high-dose clopidogrel in patients after cardiopulmonary resuscitation (CPR). European Journal of Clinical Pharmacology, 69(3), 309–317. https://doi.org/10.1007/s00228-012-1360-0
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