Clopidogrel (Lexi-Drugs)

ALERT: US Boxed Warning
  Diminished antiplatelet effect in patients with two loss-of-function alleles of the CYP2C19 gene:
Pronunciation

(kloh PID oh grel)

Brand Names: US

Plavix

Brand Names: Canada

Abbott-Clopidogrel [DSC]; ACCEL-Clopidogrel [DSC]; ACT Clopidogrel; APO-Clopidogrel; Auro-Clopidogrel; DOM-Clopidogrel; JAMP-Clopidogrel; Mar-Clopidogrel; MINT-Clopidogrel; MYLAN-Clopidogrel [DSC]; Plavix; PMS-Clopidogrel; RAN-Clopidogrel; RIVA-Clopidogrel; SANDOZ Clopidogrel; TEVA-Clopidogrel

Dosing: Adult

Acute coronary syndrome (ACS): Oral:

Unstable angina, non-ST-segment elevation myocardial infarction (UA/NSTEMI) (also referred to as NSTE-ACS): Initial: 300 mg or 600 mg loading dose, followed by 75 mg once daily for up to 12 months in combination with aspirin, followed by aspirin indefinitely (ACC/AHA [Amsterdam 2014]). Note: If patient is to undergo PCI, see Percutaneous coronary intervention (PCI) for acute coronary syndrome dosing.

ST-segment elevation myocardial infarction (STEMI) receiving fibrinolytic therapy (in combination with aspirin and appropriate anticoagulant) (ACCF/AHA [O’Gara 2013]): Note: If patient is to undergo primary PCI, see Percutaneous coronary intervention (PCI) for acute coronary syndrome dosing.

Age ≤75 years: Loading dose of 300 mg followed by 75 mg once daily for at least 14 days up to 1 year (in the absence of bleeding).

Age >75 years: 75 mg once daily (no loading dose) for at least 14 days up to 1 year (in the absence of bleeding).

Percutaneous coronary intervention (PCI) for acute coronary syndrome (eg, NSTE-ACS or STEMI) (off-label use): 600 mg (loading dose) given as early as possible before or at the time of PCI, followed by 75 mg once daily (in combination with aspirin) for at least 12 months (bare metal or drug-eluting stent) (ACC/AHA [Amsterdam 2014]); ACC/AHA [Levine 2016]; ACCF/AHA/SCAI [Levine 2011]; ACCF/AHA [O’Gara 2013]).

PCI after fibrinolytic therapy (ACCF/AHA [O’Gara 2013]):

Fibrinolytic administered with a loading dose of clopidogrel: Continue 75 mg once daily and do not administer an additional loading dose.

Fibrinolytic administered within previous 24 hours without a loading dose of clopidogrel: Administer 300 mg loading dose before or at the time of PCI.

Fibrinolytic administered more than 24 hours ago without a loading dose of clopidogrel: Administer 600 mg loading dose before or at the time of PCI.

Higher versus standard maintenance dosing: May consider a maintenance dose of 150 mg once daily for 6 days, then 75 mg once daily thereafter in patients not at high risk for bleeding (CURRENT-OASIS 7 Investigators 2010); however, in another study, in patients with high on-treatment platelet reactivity, the use of 150 mg once daily for 6 months did not demonstrate a difference in 6-month incidence of death from cardiovascular causes, nonfatal MI, or stent thrombosis compared to standard dose therapy (Price 2011).

Duration of clopidogrel (in combination with aspirin) after stent placement for ACS: Premature interruption of therapy may result in stent thrombosis with subsequent fatal and nonfatal MI. According to the ACC/AHA Duration of Dual Antiplatelet Therapy (DAPT) guidelines, at least 12 months of a P2Y12 inhibitor (eg, clopidogrel) is recommended for those with ACS receiving either stent type (bare metal [BMS] or drug eluting stent [DES]). The DAPT score may be useful in determining whether to prolong or extend DAPT in patients with stent placement (Yeh 2016). In patients with DES placement with a high risk of bleeding or significant overt bleeding on DAPT, it may be reasonable to discontinue clopidogrel after 6 months of therapy (ACC/AHA [Levine 2016]).

CYP2C19 poor metabolizers (ie, CYP2C19*2 or *3 carriers): Although routine genetic testing is not recommended in patients treated with clopidogrel undergoing PCI, testing may be considered to identify poor metabolizers who would be at risk for poor outcomes while receiving clopidogrel; if identified, these patients may be considered for an alternative P2Y12 inhibitor (Levine 2011). An appropriate regimen for this patient population has not been established in clinical outcome trials. Although a 600 mg loading dose, followed by 150 mg once daily produced greater active metabolite exposure and antiplatelet response compared to the 300 mg/75 mg regimen, it does not appear that this dosing strategy improves outcomes for this patient population (Price 2011; Simon 2011).

Carotid artery stenosis, symptomatic (including recent carotid endarterectomy) (off-label use): Oral: 75 mg once daily (ACCP [Guyatt 2012])

Coronary artery bypass graft surgery (secondary prevention) (off-label use) (AHA [Kulik 2015]):

Following off-pump CABG: 75 mg once daily (in combination with aspirin) for 1 year

Aspirin-allergic or -intolerant patients: 75 mg once daily; continue indefinitely

Coronary artery disease (CAD), established (off-label use): Oral: 75 mg once daily. Note: Established CAD defined as patients 1-year post ACS, with prior revascularization, coronary stenosis >50% by angiogram, and/or evidence for cardiac ischemia on diagnostic testing (includes patients after the first year post-ACS and/or with prior CABG surgery) (ACCP [Guyatt 2012]).

Percutaneous coronary intervention (PCI), non-acute coronary syndrome (ie, stable ischemic heart disease) (off-label use): 600 mg (loading dose) given as early as possible before or at the time of PCI, followed by 75 mg once daily (in combination with aspirin) for at least 1 month (bare metal stent) or for at least 6 months (drug-eluting stent) (ACC/AHA [Levine 2016]; ACCF/AHA/SCAI [Levine 2011]).

Duration of clopidogrel (in combination with aspirin) after stent placement for stable ischemic heart disease (SIHD): Premature interruption of therapy may result in stent thrombosis with subsequent fatal and nonfatal MI. According to the ACC/AHA Duration of Dual Antiplatelet Therapy (DAPT) guidelines, those receiving a newer generation DES, at least 6 months of clopidogrel therapy is recommended. Those receiving a BMS should be given clopidogrel for a minimum of 1 month. The DAPT score may be useful in determining whether to prolong or extend DAPT in patients with stent placement (Yeh 2016). In patients with DES placement with a high risk of bleeding or significant overt bleeding on DAPT, it may be reasonable to discontinue clopidogrel after 3 months of therapy (ACC/AHA [Levine 2016]).

Peripheral artery percutaneous transluminal angioplasty (with or without stenting) or peripheral artery bypass graft surgery, postprocedure (off-label use): Oral: 75 mg once daily. Note: For below-knee bypass graft surgery with prosthetic grafts, combine with aspirin 75 to 100 mg/day (ACCP [Guyatt 2012]).

Recent MI, recent stroke, or established peripheral arterial disease (PAD): Oral: 75 mg once daily.

Guideline recommendations regarding concomitant therapy and durations of therapy (off-label):

Minor ischemic stroke or TIA, secondary prevention: The combination of clopidogrel and aspirin might be considered within 24 hours of a minor ischemic stroke or TIA and continued for 21 days (AHA/ASA [Kernan 2014]).

Intracranial atherosclerosis (70% to 99% stenosis of a major intracranial artery), secondary prevention: The combination of clopidogrel and aspirin for 90 days is recommended in patients with recent stroke/TIA (within 30 days) due to severe stenosis [70% to 99%]) (AHA/ASA [Kernan 2014]).

PAD: Clopidogrel is recommended as an alternative to aspirin or in conjunction with aspirin for those who are not at an increased risk of bleeding but are of high cardiovascular risk. These recommendations also pertain to those with intermittent claudication or critical limb ischemia, prior lower extremity revascularization, or prior amputation for lower extremity ischemia (ACCF/AHA [Rooke 2011]).

Secondary prevention of cardiovascular disease (patients with diabetes and an aspirin allergy) (off-label use): Oral: 75 mg once daily (ADA 2019)

Transcatheter aortic valve replacement (TAVR) (thromboprophylaxis) (off-label use): Oral:

Pre-procedure:

Clopidogrel naive: 300 mg on the day of procedure.

Clopidogrel experienced: Continue clopidogrel 75 mg once daily prior to procedure (Kalich 2018).

Post-procedure:

Not on anticoagulation post-procedure: 75 mg once daily for 3 to 6 months depending on valve type and patient-specific risks of bleeding or thrombosis plus life-long aspirin (Otto 2017).

On anticoagulation post-procedure: Practice varies and local protocols should be established. It may be reasonable to use anticoagulation (warfarin or a non-warfarin oral anticoagulant) plus life-long aspirin or clopidogrel 75 mg once daily for 3 to 6 months followed by life-long aspirin (eg, not dual antiplatelet therapy) (Kalich 2018).

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

No dosage adjustment necessary (Basra 2011). Note: GFR stage 5 (ie, ESRD or an eGFR <15 mL/minute) is associated with higher residual platelet reactivity with maintenance dosing (Muller 2012).

Hemodialysis: Not dialyzable (NCS/SCCM [Frontera 2016])

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

Antiplatelet effect: Limited data available:

Infants and Children ≤24 months: In the PICOLO trial, a dose of 0.2 mg/kg/dose once daily was found to achieve a mean inhibition of platelet aggregation similar to adults receiving the recommended dose; Note: This study included pediatric patients with a systemic-to-pulmonary artery shunt, intracardiac or intravascular stent, Kawasaki disease, or arterial graft; 79% of patients received concomitant aspirin (Li 2008).

Children >2 years and Adolescents: Initial dose: 1 mg/kg once daily; titrate to response; in general, do not exceed adult dose (Finkelstein 2005; Soman 2006).

CYP2C19 poor metabolizers (ie, CYP2C19*2 or *3 carriers): Specific pediatric recommendations are lacking; based on experience in adult patients, routine genetic testing is not recommended in patients treated with clopidogrel undergoing PCI, testing may be considered to identify poor metabolizers who would be at risk for poor outcomes while receiving clopidogrel; if identified, these patients may be considered for an alternative P2Y12 inhibitor (Levine 2011).

Dosing: Renal Impairment: Pediatric

No dosage adjustment is required; use with caution; experience in pediatric patients is limited; in adults, GFR stage 5 (ie, ESRD or an eGFR <15 mL/minute) is associated with higher residual platelet reactivity with maintenance dosing (Muller 2012).

Dosing: Hepatic Impairment: Pediatric

There are no specific recommendations in pediatric patients; in adults, no dosage adjustment is necessary.

Use: Labeled Indications

Acute coronary syndrome:

Acute ST-segment elevation myocardial infarction: To reduce the rate of myocardial infarction and stroke in conjunction with aspirin in patients with acute ST-elevation MI (STEMI) who are to be managed medically.

Unstable angina/non-ST-segment elevation myocardial infarction: To decrease the rate of MI and stroke in conjunction with aspirin in patients with non-ST-segment elevation acute coronary syndrome (unstable angina/non-ST-elevation myocardial infarction [UA/NSTEMI]), including patients who are to be managed medically and those who are to be managed with coronary revascularization.

Recent myocardial infarction, recent stroke, or established peripheral arterial disease: To reduce the rate of MI and stroke in patients with a history of recent MI, recent stroke, or established peripheral arterial disease.

Use: Off-Label: Adult

  Adjunctive therapy to support reperfusion with primary percutaneous coronary interventionLevel of Evidence [A, G]

Data from a prospective, randomized, double-blind, placebo-controlled trial supports the use of clopidogrel as an adjunctive therapy in this setting Ref. Additionally, a smaller study conducted in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI demonstrated a reduction in infarct size (primary endpoint) with a 600 mg loading dose versus a 300 mg loading dose Ref.

Based on the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines for the management of ST-elevation myocardial infarction, clopidogrel is an effective and recommended adjunctive antithrombotic agent to support reperfusion with primary PCI.

  Coronary artery bypass graft (CABG) surgery (secondary prevention)Level of Evidence [G]

Based on the American Heart Association (AHA) scientific statement for the secondary prevention after coronary artery bypass graft surgery, clopidogrel is a reasonable alternative to aspirin for patients who are intolerant or allergic to aspirin. Additionally, in patients following off-pump CABG, clopidogrel in combination with aspirin should be administered for 1 year to reduce graft occlusion. In patients following on-pump CABG (without recent acute coronary syndrome), clopidogrel in combination with aspirin may be considered but benefits are not well established.

  Non-ST-elevation acute coronary syndromes in patients with allergy or major gastrointestinal intolerance to aspirinLevel of Evidence [G]

Based on the American Heart Association/American College of Cardiology (AHA/ACC) guidelines for the management of patients with non-ST-elevation acute coronary syndromes (NSTE-ACS), clopidogrel (given initially and continued indefinitely) may be used as an alternative for patients with allergy or major gastrointestinal intolerance to aspirin.

  Percutaneous coronary intervention (PCI), non-acute coronary syndrome (ie, stable ischemic heart disease)Level of Evidence [G]

Based on the 2011 American College of Cardiology Foundation/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACCF/AHA/SCAI) percutaneous coronary intervention guidelines, clopidogrel is an effective and recommended adjunctive oral antithrombotic agent for patients with non-ACS (ie, stable ischemic heart disease [SIHD]) undergoing PCI.

  Peripheral artery percutaneous transluminal angioplastyLevel of Evidence [G]

Based on the American College of Chest Physicians (ACCP) guidelines for antithrombotic therapy and prevention of thrombosis, clopidogrel is an effective and recommended treatment option for patients undergoing peripheral artery percutaneous transluminal angioplasty with or without stenting.

  Secondary prevention of cardiovascular disease (patients with diabetes and an aspirin allergy)Level of Evidence [G]

Based on the American Diabetes Association (ADA) Standards of Medical Care in Diabetes, clopidogrel is effective and recommended for the secondary prevention of cardiovascular disease in patients with diabetes and atherosclerotic disease who have a documented aspirin allergy.

  Symptomatic carotid artery stenosis (including recent carotid endarterectomy)Level of Evidence [G]

Based on the American College of Chest Physicians (ACCP) guidelines for antithrombotic therapy and prevention of thrombosis, clopidogrel is effective and recommended for patients with symptomatic carotid stenosis (including recent carotid endarterectomy).

  Transcatheter aortic valve replacement (thromboprophylaxis)Level of Evidence [B, G]

Data from prospective, randomized trials of transcatheter aortic valve replacement (TAVR) versus surgical valve replacement Ref or TAVR versus standard non-surgical therapy Ref utilized periprocedure antithrombotic strategies that may include clopidogrel, aspirin, or anticoagulation.

Based on the 2017 American Heart Association/American College of Cardiology (AHA/ACC) focused update of the 2014 guideline for the management of patients with valvular heart disease, clopidogrel may be reasonable for up to 6 months after TAVR in addition to life-long aspirin. The optimal post-procedure antithrombotic strategy for TAVR is unknown, especially for patients who require concomitant anticoagulation. Various antithrombotic regimens are still under investigation. Clinicians should consider patient specific risks for bleeding and thrombosis when making pharmacotherapy plans Ref.

Level of Evidence Definitions
  Level of Evidence Scale
Clinical Practice Guidelines

Coronary Artery Bypass Graft:

“AHA Scientific Statement, Secondary Prevention After Coronary Artery Bypass Graft Surgery,” February 2015

ACCF/AHA, “2011 Guideline for Coronary Artery Bypass Graft Surgery,” November 2011

Coronary Artery Stent Thrombosis Prevention:

ACC/AHA “Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease,” March 2016

AHA/ACC/SCAI/ACS/ADA Science Advisory, “Prevention of Premature Discontinuation of Dual Antiplatelet Therapy in Patients With Coronary Artery Stents,” February 2007

Diabetes Mellitus:

American Diabetes Association, “Standards of Medical Care in Diabetes – 2019,” January 2019

Ischemic Heart Disease:

ACC/AHA/AATS/PCNA/SCAI/STS, “2014 Focused Update of the Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” July 2014

ACCF/AHA/ACP/AATS/PCNA/SCAI/STS, “2012 Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease,” November 2012

Non-ST-Elevation Acute Coronary Syndromes

AHA/ACC, “2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes,” September 2014.

Percutaneous Coronary Intervention:

ACCF/AHA/SCAI, “2011 Guideline for Percutaneous Coronary Intervention,” November 2011

Peripheral Arterial Disease:

ACC/AHA, “2005 Guidelines for the Management of Patients with Peripheral Arterial Disease,” March 2006

ACCF/AHA, “2011 Focused Update of the Guideline for the Management of Patients with Peripheral Artery Disease (Updating the 2005 Guideline),” September 2011

Prevention:

AHA/ACCF, “Secondary Prevention and Risk Reduction Therapy for Patients with Coronary and Other Atherosclerotic Vascular Disease: 2011 Update,” November 2011

Proton Pump Inhibitors & Thienopyridines:

ACCF/ACG/AHA, “2010 Expert Consensus Document on the Concomitant Use of Proton Pump Inhibitors and Thienopyridines,” December 2010

ST-Elevation Myocardial Infarction:

ACCF/AHA, “2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction,” December 2012.

Stroke:

AHA/ASA, “Guidelines for Prevention of Stroke in Patients with Stroke and Transient Ischemic Attack,” May 2014.

AHA/ASA, “Guidelines for the Prevention of Stroke in Women,” 2014

Surgery:

ACC/AHA, “2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery,” August 2014

STS, “2012 Update to the Society of Thoracic Surgeons Guideline on Use of Antiplatelet Drugs in Patients Having Cardiac and Noncardiac Operations,” November 2012

Valvular Heart Disease:

AHA/ACC, “2017 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease,” 2017

AHA/ACC, “2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease,” March 2014

Other:

American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th Edition), February 2012

Canadian Cardiovascular Society, “The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines,” May 2011

Canadian Cardiovascular Society, “Focused 2012 Update of the Canadian Cardiovascular Society Guidelines for the Use of Antiplatelet Therapy,” November 2013

Administration: Oral

Administer without regard to meals.

Administration: Pediatric

Oral: May be administered without regard to food.

Dietary Considerations

Avoid or minimize the consumption of grapefruit juice (Holmberg 2013).

Storage/Stability

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Extemporaneously Prepared

A 5 mg/mL oral suspension may be made using tablets. Crush four 75 mg tablets and reduce to a fine powder. Add a small amount of a 1:1 mixture of Ora-Sweet® and Ora-Plus® and mix to a uniform paste; mix while adding the vehicle in geometric proportions to almost 60 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 60 mL. Label “shake well”. Stable 60 days at room temperature or under refrigeration.

Skillman KL, Caruthers RL, and Johnson CE, “Stability of an Extemporaneously Prepared Clopidogrel Oral Suspension,” Am J Health Syst Pharm, 2010, 67(7):559-61.[PubMed 20237383]

Medication Patient Education with HCAHPS Considerations

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), pinpoint red spots on skin, tachycardia, severe abdominal pain, severe nausea, severe vomiting, severe headache, shortness of breath, confusion, seizures, or signs of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (bruising or bleeding; severe loss of strength and energy; dark urine or jaundice; pale skin; change in amount of urine passed; vision changes; change in strength on one side is greater than the other, difficulty speaking or thinking, or change in balance; or fever) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Medication Safety Issues
  Sound-alike/look-alike issues:
Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020839s067lbl.pdf#page=26, must be dispensed with this medication.

Contraindications

Hypersensitivity (eg, anaphylaxis) to clopidogrel or any component of the formulation; active pathological bleeding (eg, peptic ulcer, intracranial hemorrhage).

Canadian labeling: Additional contraindications (not in US labeling): Significant liver impairment or cholestatic jaundice; concomitant use of repaglinide.

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: Clopidogrel increases the risk of bleeding. Use is contraindicated in patients with active pathological bleeding (eg, peptic ulcer, intracranial hemorrhage). Additional risk factors for bleeding include age ≥75 years, propensity to bleed (eg, recent trauma or surgery, recent or recurrent GI bleeding, active peptic ulcer disease, severe hepatic impairment), body weight <60 kg, CABG or other surgical procedure, concomitant use of medications that increase risk of bleeding (eg, warfarin, NSAIDs). Use with caution in patients with platelet disorders, bleeding disorders and/or at increased risk for bleeding. Bleeding should be suspected if patient becomes hypotensive after undergoing recent coronary angiography, PCI, CABG, or other surgical procedure even if overt signs of bleeding do not exist. It may be possible to restore hemostasis by administering exogenous platelets; however, platelet transfusions within 4 hours of the loading dose or 2 hours of the maintenance dose may be less effective.

• Thienopyridine hypersensitivity: Because of structural similarities, cross-reactivity has been reported among the thienopyridines (clopidogrel, prasugrel, and ticlopidine); use with caution or avoid in patients with hypersensitivity or hematologic reactions to previous thienopyridine use. Use of clopidogrel is contraindicated in patients with hypersensitivity to clopidogrel. Although desensitization may be considered for mild-to-moderate hypersensitivity, do not desensitize patients with prior life-threatening allergic reactions to clopidogrel (eg, toxic epidermal necrolysis, exfoliative dermatitis, Stevens-Johnson syndrome, TTP) (Lokhandwala 2011).

• Thrombotic thrombocytopenic purpura (TTP): Cases of TTP (usually occurring within the first 2 weeks of therapy), resulting in some fatalities, have been reported; urgent plasmapheresis is required.

Disease-related concerns:

• Lacunar stroke: In patients with recent lacunar stroke (within 180 days), the use of clopidogrel in addition to aspirin did not significantly reduce the incidence of the primary outcome of stroke recurrence (any ischemic stroke or intracranial hemorrhage) compared to aspirin alone; the use of clopidogrel in addition to aspirin did however increase the risk of major hemorrhage and the rate of all-cause mortality (SPS3 Investigators, 2012).

• Renal impairment: Use with caution in patients with moderate to severe renal impairment (experience is limited).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• CYP2C19 poor metabolizers: [US Boxed Warning]: Effectiveness of clopidogrel results from its antiplatelet activity, which is dependent on its conversion to an active metabolite by the CYP-450 system, principally CYP2C19. In patients who are homozygous for nonfunctional alleles of the CYP2C19 genes (termed “CYP2C19 poor metabolizers”), clopidogrel at recommended doses forms less of the active metabolite and has a reduced effect on platelet activity. 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. Genetic testing may be considered prior to initiating clopidogrel in patients at moderate or high risk for poor outcomes (eg, PCI in patients with extensive and/or very complex disease). The optimal dose for CYP2C19 poor metabolizers has yet to be determined. After initiation of clopidogrel, functional testing (eg, VerifyNow P2Y12 assay) may also be done to determine clopidogrel responsiveness (Holmes 2010).

• Lower GI bleed patients: An individualized and multidisciplinary approach should be utilized to determine therapy discontinuation and management in patients with acute lower GI bleed (LGIB) who are on antiplatelet medications; risk of ongoing bleeding should be weighed with risk of thromboembolic events. In patients receiving dual antiplatelet therapy (aspirin plus P2Y12 receptor blocker [eg, clopidogrel, prasugrel, ticagrelor, ticlopidine]) or thienopyridine monotherapy, the thienopyridine should generally be resumed as soon as possible and at least within 7 days, taking into account control of bleeding and cardiovascular risk (aspirin should not be discontinued); however, dual antiplatelet therapy should not be discontinued in the 90 days post-acute coronary syndrome or 30 days post-coronary stenting (Strate 2016).

• Surgical patients: In patients undergoing elective surgery, consider discontinuing 5 days before surgery (except in patients with cardiac stents that have not completed their full course of dual antiplatelet therapy; patient-specific situations need to be discussed with cardiologist; AHA/ACC/SCAI/ACS/ADA Science Advisory provides recommendations) (Grines 2007). Elective noncardiac surgery should not be performed in patients in whom dual antiplatelet therapy (DAPT) will need to be discontinued perioperatively within 30 days following bare metal stent (BMS) placement or within 12 months after drug-eluting stent (DES) placement. In patients undergoing urgent non-cardiac surgery during the first 4 to 6 weeks after BMS or DES placement, continue DAPT. In patients with stents undergoing surgery that requires discontinuation of the P2Y12 inhibitor (eg, clopidogrel), continue aspirin and re-start the P2Y12 inhibitor as soon as possible after surgery (ACC/AHA [Fleisher 2014]). In patients undergoing elective CABG, discontinue clopidogrel at least 5 days before procedure; when urgent CABG is necessary, the ACC/AHA CABG guidelines recommend discontinuation for at least 24 hours prior to surgery (ACC/AHA [Hillis 2011]). The ACC/AHA STEMI guidelines recommend discontinuation for at least 24 hours prior to on-pump CABG if possible; off-pump CABG may be performed within 24 hours of clopidogrel administration if the benefits of prompt revascularization outweigh the risks of bleeding (ACC/AHA [O’Gara 2013]).

Other warnings/precautions:

• Coronary artery stents: Premature interruption of therapy may result in stent thrombosis with subsequent fatal and nonfatal MI. Duration of therapy, in general, is determined by the type of stent placed (bare metal or drug eluting) and whether an ACS event was ongoing at the time of placement (ACC/AHA [Levine 2016]; AHA/ACC/SCAI/ACS/ADA [Grines 2007]).

Geriatric Considerations

Plasma concentrations of the main metabolite of clopidogrel were significantly higher in the elderly (≥75 years). This was not associated with changes in bleeding time or platelet aggregation. No dosage adjustment is recommended.

Pregnancy Considerations

Information related to use during pregnancy is limited (Bauer 2012; De Santis 2011; Myers 2011). Based on available data, an increased risk of major birth defects, miscarriage, or adverse fetal outcomes has not been associated with maternal use of clopidogrel. According to the manufacturer, use should not be withheld if needed for emergent treatment of stroke or myocardial infarction during pregnancy. Discontinue use 5 to 7 days prior to labor, delivery, or neuraxial blockade if possible due to increased risk of maternal bleeding and hemorrhage.

Available guidelines recommend using clopidogrel only when strictly needed and for the shortest duration possible until additional fetal safety data are available (ESC [Regitz-Zagrosek 2018]).

Breast-Feeding Considerations

It is not known if clopidogrel is present in breast milk.

Adverse events have not been reported in breastfed infants (limited data). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Briggs’ Drugs in Pregnancy & Lactation
Adverse Reactions

As with all drugs that may affect hemostasis, bleeding is associated with clopidogrel. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents that alter hemostasis and patient susceptibility.

1% to 10%:

Gastrointestinal: Gastrointestinal hemorrhage (2%)

Hematologic & oncologic: Minor hemorrhage (4% to 5%), major hemorrhage (1% to 4%)

Frequency not defined:

Hematologic & oncologic: Hematoma

Respiratory: Epistaxis

<1%, postmarketing, and/or case reports: Abnormal hepatic function tests, acute generalized exanthematous pustulosis, acute hepatic failure, ageusia, agranulocytosis, anaphylactoid reaction, angioedema, aplastic anemia, arthralgia, arthritis, bronchospasm, bullous rash, colitis (including ulcerative or lymphocytic), confusion, diarrhea, DRESS syndrome, drug-induced hypersensitivity, duodenal ulcer, eczema, eosinophilic pneumonitis, erythema multiforme, erythematous rash, exfoliative dermatitis, fever, gastric ulcer, hallucination, headache, hemophilia A (acquired), hepatitis (noninfectious), hypersensitivity reaction, hypotension, increased serum creatinine, interstitial pneumonitis, intracranial hemorrhage, lichen planus, maculopapular rash, myalgia, pancreatitis, pancytopenia, pruritus, serum sickness, Stevens-Johnson syndrome, stomatitis, taste disorder, thrombotic thrombocytopenic purpura, toxic epidermal necrolysis, urticaria, vasculitis

Allergy and Idiosyncratic Reactions
Metabolism/Transport Effects

Substrate of CYP2C19 (major), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, CYP2B6 (weak), CYP2C8 (moderate)

Drug Interactions 

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy

Amiodarone: May decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy

Amodiaquine: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Amodiaquine. Risk X: Avoid combination

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy

Apixaban: Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk D: Consider therapy modification

BuPROPion: CYP2B6 Inhibitors (Weak) may increase the serum concentration of BuPROPion. Risk C: Monitor therapy

Calcium Channel Blockers: May diminish the therapeutic effect of Clopidogrel. Exceptions: Clevidipine. Risk C: Monitor therapy

Cangrelor: May diminish the antiplatelet effect of Clopidogrel. More specifically, while the use of Cangrelor is expected to increase total platelet inhibition in patients who have previously received Clopidogrel, Cangrelor is expected to decrease binding of Clopidogrel metabolites to P2Y12 receptors and thus reduce the extent of irreversible platelet inhibition. Management: Avoid administration of clopidogrel until cangrelor infusion is discontinued. Risk D: Consider therapy modification

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Risk C: Monitor therapy

CYP2C19 Inducers (Strong): May increase serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy

CYP2C19 Inhibitors (Moderate): May decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a moderate CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Risk D: Consider therapy modification

CYP2C19 Inhibitors (Strong): May decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to a risk for impaired clopidogrel effectiveness with such a combination, carefully consider the need for a strong CYP2C19 inhibitor in patients receiving clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Risk D: Consider therapy modification

CYP2C8 Substrates (High risk with Inhibitors): CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Dabigatran Etexilate: Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Antiplatelet Agents (P2Y12 Inhibitors) may increase the serum concentration of Dabigatran Etexilate. Specifically, clopidogrel may increase dabigatran serum concentrations. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk D: Consider therapy modification

Dasabuvir: Clopidogrel may increase the serum concentration of Dasabuvir. Risk C: Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy

Edoxaban: Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider the anticipated risks and benefits of this combination. If combined, increased monitoring for bleeding is recommended. Risk D: Consider therapy modification

Erythromycin (Systemic): May diminish the antiplatelet effect of Clopidogrel. Risk C: Monitor therapy

Esomeprazole: May diminish the antiplatelet effect of Clopidogrel. Esomeprazole may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Clopidogrel prescribing information recommends avoiding concurrent use with esomeprazole. Rabeprazole or pantoprazole may be lower-risk alternatives to esomeprazole. Risk D: Consider therapy modification

Etravirine: May decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Consider alternatives to clopidogrel in patients treated with etravirine. If combined, monitor for reduced clopidogrel effectiveness. Risk D: Consider therapy modification

Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

FentaNYL: May diminish the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). FentaNYL may decrease the serum concentration of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor therapy

FluvoxaMINE: May enhance the adverse/toxic effect of Clopidogrel. Specifically, the risk for bleeding may be increased. FluvoxaMINE may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Grapefruit Juice: May decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Advise patients receiving clopidogrel to minimize consumption of grapefruit and grapefruit juice. Consumption of three 200 mL glasses of grapefruit juice a day may substantially reduce clopidogrel antiplatelet effects. Risk D: Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk D: Consider therapy modification

Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Lansoprazole: May decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Morphine (Systemic): May diminish the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). Morphine (Systemic) may decrease the serum concentration of Antiplatelet Agents (P2Y12 Inhibitors). Management: Consider alternative anti-ischemic/analgesic therapies (eg, beta-blockers, nitroglycerin) in patients with acute coronary syndromes treated with a P2Y12 inhibitor when possible. The risks associated with other opioids are unknown. Risk D: Consider therapy modification

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased.Risk C: Monitor therapy

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: Clopidogrel may increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the concentrations of dasabuvir may increase. Risk C: Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Omeprazole: May diminish the antiplatelet effect of Clopidogrel. Omeprazole may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Clopidogrel labeling recommends avoiding concurrent omeprazole due to a possible decrease in clopidogrel effectiveness. Rabeprazole or pantoprazole may be lower-risk alternatives to omeprazole. Risk D: Consider therapy modification

PACLitaxel (Conventional): Clopidogrel may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy

PACLitaxel (Protein Bound): Clopidogrel may increase the serum concentration of PACLitaxel (Protein Bound). Risk C: Monitor therapy

Pantoprazole: May decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Due to the possible risk for impaired clopidogrel effectiveness, clinicians should carefully consider the need for proton pump inhibitor therapy in patients receiving clopidogrel. Other acid-lowering therapies do not appear to share this interaction. Risk C: Monitor therapy

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Pioglitazone: Clopidogrel may increase the serum concentration of Pioglitazone. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Repaglinide: Clopidogrel may increase the serum concentration of Repaglinide. Management: Avoid use of clopidogrel and repaglinide if possible; if the combination must be used, limit total repaglinide daily dose to no more than 4 mg. This is contraindicated in some non-US labeling. Risk D: Consider therapy modification

Rivaroxaban: Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk D: Consider therapy modification

Rosuvastatin: Clopidogrel may increase the serum concentration of Rosuvastatin. Risk C: Monitor therapy

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy

Selexipag: CYP2C8 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Selexipag. CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Selexipag. Management: If initiating selexipag in a patient on a moderate CYP2C8 inhibitor, consider a less frequent dosing regimen (ie, once daily). If initiating a moderate CYP2C8 inhibitor in a patient on selexipag, consider a selexipag dose reduction. Risk D: Consider therapy modification

Sodium Zirconium Cyclosilicate: May decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Separate the administration of sodium zirconium cyclosilicate and clopidogrel by at least 2 hours. Risk D: Consider therapy modification

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Warfarin: Clopidogrel may enhance the anticoagulant effect of Warfarin. Risk D: Consider therapy modification

Food Interactions

Consumption of three 200 mL glasses of grapefruit juice a day may substantially reduce clopidogrel antiplatelet effects. Management: Avoid or minimize the consumption of grapefruit or grapefruit juice (Holmberg 2013).

Monitoring Parameters

Signs of bleeding; hemoglobin and hematocrit periodically.

Advanced Practitioners Physical Assessment/Monitoring

Obtain CBC periodically. Assess for signs and symptoms of bleeding. Assess bleeding risk for patients with atrial fibrillation prior to initiation (Canadian labeling). Consider genetic testing of CYP2C19 alleles if thrombotic event occurs during therapy; alternative treatment may be needed for poor metabolizers. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor for and educated patient to report signs and symptoms of bleeding. Educate cardiac patients about adherence to therapy; avoid discontinuation for any procedures without consultation with patient’s cardiologist.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Plavix: 75 mg, 300 mg [DSC]

Generic: 75 mg, 300 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Plavix: 75 mg, 300 mg

Generic: 75 mg, 300 mg

Anatomic Therapeutic Chemical (ATC) Classification
  • B01AC04
Generic Available (US)

Yes

Pricing: US

Tablets (Clopidogrel Bisulfate Oral)

75 mg (per each): $6.57 – $6.96

300 mg (per each): $19.27 – $27.84

Tablets (Plavix Oral)

75 mg (per each): $7.73

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Clopidogrel requires in vivo biotransformation to an active thiol metabolite. The active metabolite irreversibly blocks the P2Y12 component of ADP receptors on the platelet surface, which prevents activation of the GPIIb/IIIa receptor complex, thereby reducing platelet aggregation. Platelets blocked by clopidogrel are affected for the remainder of their lifespan (~7 to 10 days).

Pharmacodynamics/Kinetics

Onset of action: Inhibition of platelet aggregation (IPA): Dose-dependent:

300 to 600 mg loading dose: Detected within 2 hours

50 to 100 mg/day: Detected by the second day of treatment

Peak effect: Time to maximal IPA: Dose-dependent: Note: Degree of IPA based on adenosine diphosphate (ADP) concentration used during light aggregometry:

300 to 600 mg loading dose:

ADP 5 micromole/L: 20% to 30% IPA at 6 hours post administration (Montelescot 2006)

ADP 20 micromole/L: 30% to 37% IPA at 6 hours post administration (Montelescot 2006)

50 to 100 mg/day: ADP 5 micromole/L: 50% to 60% IPA at 5 to 7 days (Herbert 1993)

Duration of action: Platelet aggregation and bleeding time gradually return to baseline after ~5 days after discontinuation.

Absorption: Rapid, well absorbed

Protein binding: Parent drug: 98%; Inactive metabolite (carboxylic acid derivative): 94%

Metabolism: Extensively hepatic via esterase-mediated hydrolysis to a carboxylic acid derivative (inactive) and via CYP450-mediated (CYP2C19 primarily) oxidation to a thiol metabolite (active)

Half-life elimination: Parent drug: ~6 hours; Thiol derivative (active metabolite): ~30 minutes; carboxylic acid derivative (inactive; main circulating metabolite): ~8 hours; Note: A clopidogrel radiolabeled study has shown that covalent binding to platelets accounts for 2% of radiolabel and has a half-life of 11 days.

Time to peak, serum: ~0.75 hours

Excretion: Following administration of a single 14C-labeled clopidogrel oral dose; radioactivity measured over 5 days: Urine (50%); feces (46%)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: After repeated doses of clopidogrel 75 mg/day, patients with severe (CrCl 5 to 15 mL/minute) and moderate (CrCl 30 to 60 mL/minute) renal impairment showed low (25%) inhibition of ADP-induced platelet aggregation.

Gender: Less inhibition of ADP-induced platelet aggregation was observed in women.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

There is no scientific evidence to warrant the discontinuance of clopidogrel prior to dental surgery. Patients taking one clopidogrel tablet daily as an antithrombotic and who require dental surgery should be given special consideration in consultation with physician.

Effects on Dental Treatment

Aspirin in combination with clopidogrel (Plavix®), prasugrel (Effient®), or ticagrelor (Brilinta™) is the primary prevention strategy against stent thrombosis after placement of drug-eluting metal stents in coronary patients. Premature discontinuation of combination antiplatelet therapy (ie, dual antiplatelet therapy) strongly increases the risk of a catastrophic event of stent thrombosis leading to myocardial infarction and/or death, so says a science advisory issued in January 2007 from the American Heart Association in collaboration with the American Dental Association and other professional healthcare organizations. The advisory stresses a 12-month therapy of dual antiplatelet therapy after placement of a drug-eluting stent in order to prevent thrombosis at the stent site. Any elective surgery should be postponed for 1 year after stent implantation, and if surgery must be performed, consideration should be given to continuing the antiplatelet therapy during the perioperative period in high-risk patients with drug-eluting stents.

This advisory was issued from a science panel made up of representatives from the American Heart Association (AHA), the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions, the American College of Surgeons, the American Dental Association (ADA), and the American College of Physicians (Grines, 2007).

Effects on Bleeding

Clopidogrel irreversibly inhibits platelet aggregation which persists for the life of the platelet (7-10 days) and until new platelets are released. Clopidogrel should not be discontinued in patients with cardiac stents that have not completed their full course of dual antiplatelet therapy (eg, aspirin and clopidogrel [prasugrel or ticagrelor]); patient-specific situations need to be discussed with cardiologist. If normal platelet function is desired, clopidogrel should be discontinued for at least 5 days. A medical consult is recommended to determine the benefit:risk of continuing or discontinuing clopidogrel therapy for invasive dental procedures.

Index Terms

Clopidogrel Bisulfate; Clopidogrel Hydrogen Sulfate

FDA Approval Date
November 17, 1997
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Jeske AH, Suchko GD, ADA Council on Scientific Affairs and Division of Science, et al, “Lack of a Scientific Basis for Routine Discontinuation of Oral Anticoagulation Therapy Before Dental Treatment,” J Am Dent Assoc, 2003, 134(11):1492-7.[PubMed 14664269 ]

Juurlink DN, Gomes T, Ko DT, et al, “A Population-Based Study of the Drug Interaction Between Proton Pump Inhibitors and Clopidogrel,” CMAJ, 2009, 180(7):713-8.[PubMed 19176635]

Kalich BA, Allender JE, Hollis IB. Medication management of patients undergoing transcatheter aortic valve replacement. Pharmacotherapy. 2018;38(1):122-138. doi: 10.1002/phar.2056.[PubMed 29121410]

Kastrati A, Mehilli J, Schuhlen H, et al, “A Clinical Trial of Abciximab in Elective Percutaneous Coronary Intervention After Pretreatment With Clopidogrel,” N Engl J Med, 2004, 350(3):232-8.[PubMed 14724302]

Kernan WN, Ovbiagele B, Black HR, et al; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association [published correction appears in Stroke. 2015;46(2):e54]. Stroke. 2014;45(7):2160-2236. doi: 10.1161/STR.0000000000000024.[PubMed 24788967]

Kreutz RP, Stanek EJ, Aubert R, et al, “Impact of Proton Pump Inhibitors on the Effectiveness of Clopidogrel After Coronary Stent Placement: The Clopidogrel Medco Outcomes Study,” Pharmacotherapy, 2010, 30(8):787-96.[PubMed 20653354]

Kulik A, Ruel M, Jneid H, et al. Secondary prevention after coronary artery bypass graft surgery: a scientific statement from the American Heart Association. Circulation. 2015;131(10):927-964. doi: 10.1161/CIR.0000000000000182.[PubMed 25679302]

Lange RA and Hillis LD, “Antiplatelet Therapy for Ischemic Heart Disease,” N Engl J Med, 2004, 350(3):277-80.[PubMed 14724308]

Leon MB, Smith CR, Mack MJ, et al; PARTNER 2 Investigators. Transcatheter or surgical aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2016;374(17):1609-1620. doi: 10.1056/NEJMoa1514616.[PubMed 27040324]

Leon MB, Smith CR, Mack M, et al; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363(17):1597-1607. doi: 10.1056/NEJMoa1008232.[PubMed 20961243]

Levine GN, Bates ER, Blankenship JC, et al, “2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions,” Circulation, 2011, 124(23):e574-651.[PubMed 22064601]

Levine GN, Bates ER, Bittl JA, et al; Focused Update Writing Group. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published online March 23, 2016]. J Am Coll Cardiol. pii: S0735-1097(16)01699-5.[PubMed 27036918]

Li XQ, Andersson TB, Ahalström M, et al, “Comparison of Inhibitory Effects of the Proton Pump-Inhibiting Drugs Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole and Rabeprazole on Human Cytochrome P450 Activities,” Drug Metab Dispo, 2004, 32(8):821-7.[PubMed 15258107]

Lokhandwala J, Best PJ, Henry Y, Berger PB. Allergic reactions to clopidogrel and cross-reactivity to other agents. Curr Allergy Asthma Rep. 2011;11(1):52-57.[PubMed 20941557]

Mauri L, Kereiakes DJ, Yeh RW, et al; the DAPT Study Investigators. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents [published online ahead of print November 16, 2014]. N Engl J Med.[PubMed 25399658]

Mega JL, Close SL, Wiviott SD, et al, “Cytochrome P-450 Polymorphisms and Response to Clopidogrel,” N Engl J Med, 2009, 360(40):354-62.[PubMed 19106084]

Mehta SR, Yusuf S, Peters RJ, et al, “Effects of Pretreatment With Clopidogrel and Aspirin Followed by Long-Term Therapy in Patients Undergoing Percutaneous Coronary Intervention: The PCI-CURE Study,” Lancet, 2001, 358(9281):527-33.[PubMed 11520521]

Mishkel GJ, Aguirre FV, Ligon RW, et al, “Clopidogrel as Adjunctive Antiplatelet Therapy During Coronary Stenting,” J Am Coll Cardiol, 1999, 34(7):1884-90.[PubMed 10588198]

Montalescot G, Sideris G, Meuleman C, et al, “A Randomized Comparison of High Clopidogrel Loading Doses in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes,” J Am Coll Cardiol, 2006, 48(5):931-8.[PubMed 16949482]

Moussa I, Oetgen M, Roubin G, et al, “Effectiveness of Clopidogrel and Aspirin Versus Ticlopidine and Aspirin in Preventing Stent Thrombosis After Coronary Stent Implantation,” Circulation, 1999, 99(18):2364-6.[PubMed 10318654]

Muller C, Caillard S, Jesel L, et al. Association of estimated GFR with platelet inhibition in patients treated with clopidogrel. Am J Kidney Dis. 2012;59(6):777-785.[PubMed 22425260]

Myers GR, Hoffman MK, and Marshall ES, “Clopidogrel Use Throughout Pregnancy in a Patient With a Drug-Eluting Coronary Stent,” Obstet Gynecol, 2011, 118(2 Pt 2):432-3.[PubMed 21768844]

Nishimura RA, Otto CM, Bonow RO, et al. 2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;70(2):252-289. doi: 10.1016/j.jacc.2017.03.011.[PubMed 28315732]

Nishimura RA, Otto CM, Bonow RO, et al, 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(23):2440-92. doi: 10.1161/CIR.0000000000000029.[PubMed 24589852]

O’Donoghue ML, Braunwald E, Antman EM, et al, “Pharmacodynamic Effect and Clinical Efficacy of Clopidogrel and Prasugrel with or without a Proton-pump Inhibitor: an Analysis of Two Randomised Trials,” Lancet, 2009, 374(9694):989-97.[PubMed 19726078]

Ogilvie BW, Yerino P, Kazmi F, et al, “The Proton Pump Inhibitor, Omeprazole, but not Lansoprazole or Pantoprazole, is a Metabolism-Dependent Inhibitor of CYP2C19: Implications for Coadministration With Clopidogrel,” Drug Metab Dispos, 2011, 39(11):2020-33.[PubMed 21795468]

O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines [published correction appears in Circulation. 2013;128(25):e481.] Circulation. 2013;127(4):e362-425.[PubMed 23247304]

Otto CM, Kumbhani DJ, Alexander KP, et al. 2017 ACC expert consensus decision pathway for transcatheter aortic valve replacement in the management of adults with aortic stenosis: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2017;69(10):1313-1346. doi: 10.1016/j.jacc.2016.12.006.[PubMed 28063810]

Patti G, Colonna G, Pasceri V, et al, “Randomized Trial of High Loading Dose of Clopidogrel for Reduction of Periprocedural Myocardial Infarction in Patients Undergoing Coronary Intervention: Results From the ARMYDA-2 (Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty) Study,” Circulation, 2005, 111(16):2099-106.

Patti G, Bárczi G, Orlic D, et al. Outcome comparison of 600- and 300-mg loading doses of clopidogrel in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2011;58(15),1592-1599.[PubMed 21958886]

Pezalla E, Day D, and Pulliadath I, “Initial Assessment of Clinical Impact of a Drug Interaction Between Clopidogrel and Proton Pump Inhibitors,” J Am Coll Cardiol, 2008, 52(12):1038-9.

Plavix (clopidogrel) [prescribing information]. Bridgewater, NJ: Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership; October 2018.

Plavix (clopidogrel) [product monograph]. Laval, Quebec, Canada: Sanofi-Aventis Canada Inc; February 2019.

Price MJ, Berger PB, Teirstein PS, et al, “Standard- Vs High-Dose Clopidogrel Based on Platelet Function Testing After Percutaneous Coronary Intervention: The GRAVITAS Randomized Trial,” JAMA, 2011, 305(11):1097-105.[PubMed 21406646]

Reardon MJ, Van Mieghem NM, Popma JJ, et al; SURTAVI Investigators. Surgical or transcatheter aortic-valve replacement in intermediate-risk patients. N Engl J Med. 2017;376(14):1321-1331. doi: 10.1056/NEJMoa1700456.[PubMed 28304219]

Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, et al; ESC Scientific Document Group. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39(34):3165-3241. doi: 10.1093/eurheartj/ehy340.[PubMed 30165544]

Rooke TW, Hirsch AT, Misra S, et al, “2011 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Peripheral Artery Disease (Updating the 2005 Guideline): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines,” Circulation, 2011, 124(18):2020-45.[PubMed 21959305]

Sabatine MS, Cannon CP, Gibson CM, et al, “Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction With ST-Segment Elevation,” N Engl J Med, 2005, 352(12):1179-89.[PubMed 15758000]

Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics. JAMA. 2005b;294:(10)1224-1232.[PubMed 16143698]

Scirica BM, Sabatine MS, Morrow DA, et al, “The Role of Clopidogrel in Early and Sustained Arterial Patency After Fibrinolysis for ST-segment Elevation Myocardial Infarction. The ECG Clarity-TIMI 28 Study,” J Am Coll Cardiol, 2006, 48(1):37-42.[PubMed 16814646]

Sibbing D, Koch W, Gebhard D, et al, “Cytochrome 2C19*17 Allelic Variant, Platelet Aggregation, Bleeding Events, and Stent Thrombosis in Clopidogrel-Treated Patients With Coronary Stent Placement,” Circulation, 2010, 121(4):512-18.[PubMed 20083681]

Siller-Matula JM, Spiel AO, Lang IM, et al, “Effects of Pantoprazole and Esomeprazole on Platelet Inhibition by Clopidogrel,” Am Heart J, 2009, 157(1):148.e1-5.

Sim SC, Risinger C, Dahl ML, et al, “A Common Novel CYP2C19 Gene Variant Causes Ultrarapid Drug Metabolism Relevant for the Drug Response to Proton Pump Inhibitors and Antidepressants,” Clin Pharmacol Ther, 2006, 79(1):103-13.[PubMed 16413245]

Simon T, Bhatt DL, Bergougnan L, et al. Genetic polymorphisms and the impact of a higher clopidogrel dose regimen on active metabolite exposure and antiplatelet response in healthy subjects. Clin Pharmacol Ther. 2011;90(2):287-295.[PubMed 21716274]

Small DS, Farid NA, Payne CD, et al, “Effects of the Proton Pump Inhibitor Lansoprazole on the Pharmacokinetics and Pharmacodynamics of Prasugrel and Clopidogrel,” J Clin Pharmacol, 2008, 48(4):475-84.

Smith SC Jr, Benjamin EJ, Bonow RO, et al, “AHA/ACCF Secondary Prevention and Risk Reduction Therapy for Patients With Coronary and Other Atherosclerotic Vascular Disease: 2011 Update: A Guideline From the American Heart Association and American College of Cardiology Foundation,” Circulation, 2011, 124(22):2458-73.[PubMed 22052934]

Smith CR, Leon MB, Mack MJ, et al; PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;364(23):2187-2198. doi: 10.1056/NEJMoa1103510.[PubMed 21639811]

SPS3 Investigators, “Effects of Clopidogrel Added to Aspirin in Patients With Recent Lacunar Stroke,” N Engl J Med, 2012, 367(9):817-25.[PubMed 22931315]

Steinhubl SR, Berber PB, Mann JT, et al, “Early and Sustained Dual Oral Antiplatelet Therapy Following Percutaneous Coronary Intervention. A Randomized Controlled Trial,” JAMA, 2002, 288(19):2411-20.[PubMed 12435254]

Strate LL, Gralnek IM. ACG clinical guideline: management of patients with acute lower gastrointestinal bleeding. Am J Gastroenterol. 2016;111(4):459-474. doi: 10.1038/ajg.2016.41.[PubMed 26925883]

Trenk D, Hochholzer W, Fromm MF, et al, “Cytochrome P450 2C19 681G>A Polymorphism and High On-Clopidogrel Platelet Reactivity Associated With Adverse 1-Year Clinical Outcome of Elective Percutaneous Coronary Intervention With Drug Eluting or Bare-Metal Stents,” J Am Coll Cardiol, 2008, 51(20):1925-34.[PubMed 18482659]

Wynn RL, “Clopidogrel (Plavix): Dental Considerations of an Antiplatelet Drug,” Gen Dent, 2001, 49(6):564-8.[PubMed 12024741 ]

Yeh RW, Secemsky EA, Kereiakes DJ, et al; DAPT Study Investigators. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016;315(16):1735-1749.[PubMed 27022822]

Yusuf S, Zhao F, Mehta SR, et al, “Effects of Clopidogrel in Addition to Aspirin in Patients With Acute Coronary Syndromes Without ST-Segment Elevation,” N Engl J Med, 2001, 345(7):494-502.[PubMed 11519503]

Brand Names: International

Aclop (AT); Actaclo (PH); Acuvan (PH); Agrelan (ES); Antiplar (PH); Antiplatt (ET); Apolets (TH); Arapamin (ES); Artepid (ID); Artheogrel (PH); Ateplax (EC, PE); Aterocard (UA); Atogrel (UA); Bidogrel (ZW); Bilgrel (VN); Borgavix (EG); Caplor (VN); Ceranade (KR); Ceruvin (TH); Clatex (EG); Clavix (MY); Clentel (EC); Clidorel (ID); Clo V (KR); Cloart (KR); Clodel (IE); Clodor (LB); Clofix (TW); Clogin (ID); Clogrel (BD); Clood (IL); Clopacin (CR, DO, GT, HN, NI, PA, SV); Clopid (SY); Clopidexcel (IL); Clopidolut (VN); Clopidrol (PH); Clopilet (IN); Clopimed (LK); Clopimet (PH); Clopiright (HK); Clopistad (HK); Clopitab (LK); Clopivas (HK); Clopivaz (PH); Clopivid (HK, MY); Cloprez (LK); Clorel (BD); Clotinil (TW); Clotiz (PH); Clovex (JO); Clovix (MY); Clovixx (TW); Copalex (HK); Copedina (VN); Cotol (TW); CPG (ID); Curovix (KR); Deplat (TW); Deplatt (ET, SG, ZW); Deviplat (MX); Dogrel (BD); Duopidogrel (MY); Egitromb (BG, VN); G Plus (SG); Grepid (BE, ES, HR, IE, MT, NL, TR); Gridokline (MY); Hemaflow (PH); Hogel (CO); Idiavix (EG); Insigrel (ID); Iscover (AR, AT, AU, BE, BG, BR, CH, CZ, DE, DK, EE, ES, FR, GB, GR, HR, HU, IE, IT, LT, MT, NL, NO, PL, PT, RO, RU, SE, SK, TR); Kogrel (MY); Kovix (KR); Lifextend (VN); Lopirel (HK); Maxgrel (KR); Medigrel (ID); Nabratin (CR, DO, GT, HN, NI, PA, SV); Nafamedil (VN); Noclot (PK); Nogrel (PH); Noklot (ET, PH); Panagrel (PE); Pedovex (AE, BH, QA); Piax (AU, NZ); Pidogul (KR); Pingel (UA); Plabic (KR); Placta (ID, SG); Pladogrel (ID); Plagrel (BH); Plagril (SG, UA); Plahasan (VN); Plamed (KR); Planor (TR); PlaquEx (BG); Platarex (HU); Platless (SG); Platogrix (ID); Plator (BD); Platout (TW); Plavitor (KR); Plavix (AE, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CU, CY, CZ, DE, DK, DO, EE, EG, ES, ET, FI, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, HU, ID, IE, IL, IS, IT, JM, JO, JP, KE, KR, KW, LB, LK, LR, LT, LU, LV, MA, ML, MR, MT, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, PA, PE, PH, PK, PL, PR, PT, PY, QA, RO, RU, SA, SC, SD, SE, SG, SI, SK, SL, SN, SR, SV, TH, TN, TR, TT, TW, TZ, UA, UG, UY, VE, VN, ZA, ZM, ZW); Plavos (ID); Preto (KR); Provic (KR); Q.O.L. (KR); Ravalgen (EC); Simclovix (ID); Stenvix (JO); Stroka (EG); Talcom (CN); Therodel (ID); Troken (LB, MY); Trombex (SK); Vaclo (ID); Vicafidt (MX); Vivelon (PH); Zyllt (NL)

Clopidogrel (Patient Education – Adult Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(kloh PID oh grel)

Brand Names: US

Plavix

Brand Names: Canada

Plavix

Warning
  • This drug may not work as well in some people. A test can be done to see if you are one of these people. Talk with your doctor.
What is this drug used for?
  • It is used to prevent heart attacks.
  • It is used to prevent strokes.
  • It is used after a heart treatment to protect the arteries.
  • It is used to lower the number of heart attacks in patients who have unstable angina or mild heart attacks.
  • It may be given to you for other reasons. Talk with the doctor.
What do I need to tell my doctor BEFORE I take this drug?
  • If you have an allergy to clopidogrel or any other part of this drug.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you are taking any of these drugs: Esomeprazole, omeprazole, or repaglinide.
  • If you have active bleeding.
  • If you are breast-feeding or plan to breast-feed.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this drug with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
What are some things I need to know or do while I take this drug?
  • Tell all of your health care providers that you take this drug. This includes your doctors, nurses, pharmacists, and dentists. This drug may need to be stopped before certain types of surgery as your doctor has told you. If this drug is stopped, your doctor will tell you when to start taking this drug again after your surgery or procedure.
  • Do not stop taking this drug without calling the doctor who ordered it for you.
  • If you fall or hurt yourself, or if you hit your head, call your doctor right away. Talk with your doctor even if you feel fine.
  • You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
  • Very bad and sometimes deadly bleeding problems have happened with this drug. Talk with the doctor.
  • Talk with your doctor before using products that have aspirin, blood thinners, garlic, ginseng, ginkgo, ibuprofen or like products, pain drugs, or vitamin E.
  • Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this drug while you are pregnant.
What are some side effects that I need to call my doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Very bad headache.
  • Shortness of breath.
  • Feeling confused.
  • Seizures.
  • Purple spots or redness of the skin.
  • A fast heartbeat.
  • Very bad belly pain.
  • Very upset stomach or throwing up.
  • Very bad and sometimes deadly blood problems like thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) have happened with this drug in some people. Call your doctor right away if you feel very tired or weak or have any bruising or bleeding; dark urine or yellow skin or eyes; pale skin; change in the amount of urine passed; change in eyesight; change in strength on 1 side is greater than the other, trouble speaking or thinking, or change in balance; or fever.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if you have any side effects that bother you or do not go away.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best taken?
  • Use this drug as ordered by your doctor. Read all information given to you. Follow all instructions closely.
  • Take this drug at the same time of day.
  • Take with or without food.
  • To gain the most benefit, do not miss doses.
  • Keep taking this drug as you have been told by your doctor or other health care provider, even if you feel well.
What do I do if I miss a dose?
  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses unless told to do so by your doctor.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else’s drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.
Clopidogrel (Patient Education – Pediatric Medication)
You must carefully read the “Consumer Information Use and Disclaimer” below in order to understand and correctly use this information
Pronunciation

(kloh PID oh grel)

Brand Names: US

Plavix

Brand Names: Canada

Plavix

Warning
  • This drug may not work as well in some people. A test can be done to see if your child is one of these people. Talk with the doctor.
What is this drug used for?
  • It is used to prevent heart attacks.
  • It is used to prevent strokes.
  • It is used after a heart treatment to protect the arteries.
  • It is used to lower the number of heart attacks in patients who have unstable angina or mild heart attacks.
  • It may be given to your child for other reasons. Talk with the doctor.
What do I need to tell the doctor BEFORE my child takes this drug?
  • If your child has an allergy to this drug or any part of this drug.
  • If your child is allergic to any drugs like this one or any other drugs, foods, or other substances. Tell the doctor about the allergy and what signs your child had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If your child is taking any of these drugs: Esomeprazole, omeprazole, or repaglinide.
  • If your child has active bleeding.
  • If your child is breast-feeding a baby:
  • Talk with the doctor if your child is breast-feeding a baby or plans to breast-feed a baby.
  • This is not a list of all drugs or health problems that interact with this drug.
  • Tell the doctor and pharmacist about all of your child’s drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for your child to take this drug with all of his/her drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor.
What are some things I need to know or do while my child takes this drug?
  • Tell all of your child’s health care providers that your child is taking this drug. This includes your child’s doctors, nurses, pharmacists, and dentists. This drug may need to be stopped before certain types of surgery as the doctor has told you. If this drug is stopped, the doctor will tell you when to start giving this drug again after your child’s surgery or procedure.
  • Do not stop giving this drug without calling the doctor who ordered it for your child.
  • If your child falls, gets hurt, or hits his/her head, call the doctor right away. Talk with the doctor even if your child feels fine.
  • Your child may bleed more easily. Make sure your child is careful and avoids injury. Be sure your child has a soft toothbrush.
  • Very bad and sometimes deadly bleeding problems have happened with this drug. Talk with the doctor.
  • Talk with the doctor before giving your child products that have aspirin, ibuprofen or like products, blood thinners (warfarin, ticlopidine, clopidogrel), garlic, ginseng, ginkgo, or vitamin E.
  • If your child is pregnant:
  • Tell the doctor if your child is pregnant or becomes pregnant. You will need to talk about the benefits and risks of your child using this drug while pregnant.
What are some side effects that I need to call my child’s doctor about right away?
  • WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child’s doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect:
  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
  • Very bad headache.
  • Shortness of breath.
  • Feeling confused.
  • Seizures.
  • Purple spots or redness of the skin.
  • A fast heartbeat.
  • Very bad belly pain.
  • Very upset stomach or throwing up.
  • Very bad and sometimes deadly blood problems like thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) have happened with this drug in some people. Call your child’s doctor right away if your child feels very tired or weak or has any bruising or bleeding; dark urine or yellow skin or eyes; pale skin; change in the amount of urine passed; change in eyesight; change in strength on 1 side is greater than the other, trouble speaking or thinking, or change in balance; or fever.
What are some other side effects of this drug?
  • All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child’s doctor or get medical help if your child has any side effects that bother your child or do not go away.
  • These are not all of the side effects that may occur. If you have questions about side effects, call your child’s doctor. Call your child’s doctor for medical advice about side effects.
  • You may report side effects to your national health agency.
How is this drug best given?
  • Give this drug as ordered by your child’s doctor. Read all information given to you. Follow all instructions closely.
  • Give this drug at the same time of day.
  • Give this drug with or without food.
  • To gain the most benefit, do not miss giving your child doses.
  • Keep giving this drug to your child as you have been told by your child’s doctor or other health care provider, even if your child feels well.
What do I do if my child misses a dose?
  • Give a missed dose as soon as you think about it.
  • If it is close to the time for your child’s next dose, skip the missed dose and go back to your child’s normal time.
  • Do not give 2 doses at the same time or extra doses unless told to do so by your child’s doctor.
How do I store and/or throw out this drug?
  • Store at room temperature.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area.
General drug facts
  • If your child’s symptoms or health problems do not get better or if they become worse, call your child’s doctor.
  • Do not share your child’s drug with others and do not give anyone else’s drug to your child.
  • Keep a list of all your child’s drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your child’s doctor.
  • Talk with your child’s doctor before giving your child any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child’s doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.