The effectiveness of clopidogrel results from its antiplatelet activity, which is dependent on its conversion to an active metabolite by the cytochrome P450 (CYP-450) system, principally CYP2C19. Clopidogrel at recommended doses forms less of the active metabolite and has a reduced effect on platelet activity in patients who are homozygous for nonfunctional alleles of the CYP2C19 genes (termed “CYP2C19 poor metabolizers”). 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.
Antiplatelet effect: Limited data available: Oral: 0.2 mg/kg/dose once daily. A double-blind, placebo-controlled trial of 906 patients (n=461 neonates; n=445 infants ≤3 months) with cyanotic congenital heart disease surgically treated with a systemic-to-pulmonary artery shunt did not demonstrate a clinical benefit compared to placebo. Concomitant aspirin was used in 88% of patients (NCT00396877 2011). In another trial, 0.2 mg/kg/dose once daily was found to achieve a mean inhibition of platelet aggregation similar to a standard adult dose; Note: This study (PICOLO Trial) included 73 evaluable patients (n=34 neonates [with exclusion of patients with weight <2 kg and GA <35 weeks]; n=39 infants ≤24 months) with a systemic-to-pulmonary artery shunt, intracardiac or intravascular stent, Kawasaki disease, or arterial graft; 79% of patients received concomitant aspirin (Li 2008).
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 adult 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 (ACCP [Monagle 2012]; Li 2008).
Children >2 years and Adolescents: Initial dose: 1 mg/kg once daily; in general, do not exceed adult dose (ACCP [Monagle 2012]; 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 percutaneous coronary intervention; testing may be considered to identify poor metabolizers who would be at risk for poor response while receiving clopidogrel and if identified, these patients may be considered for an alternative P2Y12 inhibitor (AHA [Levine 2011]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; use with caution. Based on adult data, no dosage adjustment is required; in adults, GFR stage 5 (ie, end-stage renal disease or an eGFR <15 mL/minute) is associated with higher residual platelet reactivity with maintenance dosing (Muller 2012).
There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling; in adults, no dosage adjustment is necessary.
(For additional information see "Clopidogrel: Drug information")
Note: In patients who require concomitant therapeutic anticoagulation, antiplatelet selection and/or duration of therapy may differ in order to balance risks for thrombosis and bleeding (ACC [Kumbhani 2021]).
Acute coronary syndrome:
Note: Routine platelet-function testing or genetic testing for CYP2C19 polymorphisms is not recommended (ACC/AHA [Levine 2016]; Scott 2013; Sibbing 2019).
ST-segment elevation myocardial infarction:
Note: Regardless of the reperfusion strategy, administer clopidogrel in combination with a parenteral anticoagulant and aspirin (ACCF/AHA [O'Gara 2013]).
If using fibrinolytic therapy for reperfusion:
Age ≤75 years: Oral: Initial loading dose: 300 mg once at the time of diagnosis; followed by 75 mg once daily (ACCF/AHA [O'Gara 2013]; Sabatine 2005a).
Age >75 years: Oral: 75 mg once daily (ACCF/AHA [O'Gara 2013]).
Patient requires percutaneous coronary intervention following fibrinolytic therapy:
Fibrinolytic administered with a clopidogrel 300 mg loading dose: Oral: Continue 75 mg once daily (do not administer an additional loading dose) (ACCF/AHA [O'Gara 2013]).
Fibrinolytic administered ≤24 hours ago without a loading dose of clopidogrel: Oral: Initial: 300 mg once prior to percutaneous coronary intervention (PCI); followed by 75 mg once daily after PCI (ACCF/AHA [O'Gara 2013]).
Fibrinolytic administered >24 hours ago without a loading dose of clopidogrel: Oral: Initial: 600 mg once prior to PCI; followed by 75 mg once daily after PCI (ACCF/AHA [O'Gara 2013]).
If using percutaneous coronary intervention for reperfusion (alternative agent) (off-label use):
Note: Some experts prefer ticagrelor or prasugrel over clopidogrel unless there is high risk for bleeding (Lincoff 2020; Wallentin 2009; Wiviott 2007).
Oral: Initial: 600 mg once as early as possible before PCI; followed by 75 mg once daily after PCI (ACCF/AHA [O'Gara 2013]; Dangas 2009; Mehta 2010).
If no planned reperfusion strategy (alternative agent):
Note: Some experts prefer ticagrelor over clopidogrel (Lincoff 2020).
Oral: Initial: 300 mg once at the time of diagnosis; followed by 75 mg once daily (Lincoff 2020).
Duration of therapy: Clopidogrel plus aspirin (dual antiplatelet therapy [DAPT]) should be continued for ≥12 months unless bleeding is a concern. If there have been no major bleeding complications after 12 months, continuation of DAPT may be considered. Reevaluate the need for DAPT at regular intervals based on bleeding and thrombotic risks. When DAPT is complete, discontinue clopidogrel and continue aspirin indefinitely (ACC/AHA [Levine 2016]; ACCF/AHA [O'Gara 2013]; Lincoff 2020; Mauri 2014).
Non-ST-segment elevation acute coronary syndromes:
Note: Regardless of the management strategy, administer clopidogrel in combination with a parenteral anticoagulant and aspirin (ACC/AHA [Amsterdam 2014]).
If using an ischemia-guided approach (medical management) (alternative agent):
Note: Some experts prefer ticagrelor over clopidogrel (Cutlip 2021a).
Oral: Initial: 300 or 600 mg once at the time of diagnosis; followed by 75 mg once daily (ACC/AHA [Amsterdam 2014]). Some experts prefer an initial dose of 600 mg unless there is high risk for bleeding, in which case, an initial dose of 300 mg is also appropriate (Cutlip 2021a).
If using an invasive approach (reperfusion using percutaneous coronary intervention) (alternative agent):
Note: Some experts prefer ticagrelor or prasugrel over clopidogrel unless there is high risk for bleeding (Cutlip 2021a; Wallentin 2009; Wiviott 2007).
Oral: Initial: 600 mg once as early as possible before PCI; followed by 75 mg once daily after PCI (ACC/AHA [Amsterdam 2014]).
Duration of therapy: Clopidogrel plus aspirin (DAPT) should be continued for ≥12 months unless bleeding is a concern. If there have been no major bleeding complications after 12 months, continuation of DAPT may be considered. Reevaluate the need for DAPT at regular intervals based on bleeding and thrombotic risks. When DAPT is complete, discontinue clopidogrel and continue aspirin indefinitely (ACC/AHA [Amsterdam 2014]; ACC/AHA [Levine 2016]; Cutlip 2021a; Mauri 2014; Mehta 2001; Yusuf 2001).
Percutaneous coronary intervention for stable ischemic heart disease (off-label use):
Note: Administer clopidogrel in combination with a parenteral anticoagulant and aspirin for patients who undergo PCI with stenting (ACCF/AHA/SCAI [Levine 2011]).
Oral: Initial: 600 mg once, administered ≥2 hours before PCI, ideally ≥24 hours before PCI; followed by 75 mg once daily (ACCF/AHA/SCAI [Levine 2011]; Cutlip 2020).
Duration of therapy : Upon completion of the recommended duration of DAPT (clopidogrel plus aspirin), discontinue clopidogrel and continue aspirin indefinitely (ACC/AHA [Levine 2016]; Cutlip 2021b):
• Bare metal stent implantation: DAPT for a minimum of 1 month (ACC/AHA [Levine 2016]). Some experts recommend at least 6 months and up to 12 months; in patients at high bleeding risk, shorter duration may be considered. After 6 to 12 months, assess bleeding and ischemic risks to determine if patient should receive longer therapy (eg, for an additional 18 to 24 months) (Cutlip 2021b).
• Drug eluting stent implantation: DAPT for at least 6 months and up to 12 months; if bleeding occurs or patient is at high risk of bleeding, may stop after 3 months (ACC/AHA [Levine 2016]). After 6 to 12 months, assess bleeding and ischemic risks to determine if patient should receive longer therapy (eg, for an additional 18 to 24 months) (Cutlip 2021b).
Carotid artery atherosclerosis, symptomatic (alternative agent) (off-label use):
Note: For patients who are intolerant of aspirin.
Oral: 75 mg once daily (ACCP [Alonso-Coello 2012]; Cucchiara 2019).
Carotid artery stenting (off-label use):
Percutaneous approach:
Initial:
Initiation ≥48 hours before procedure: Oral: 75 mg twice daily in combination with aspirin (Brott 2010).
Initiation <48 hours before procedure: Oral: 450 mg once at least 4 hours before procedure in combination with aspirin (Brott 2010).
Maintenance: Oral: 75 mg once daily in combination with aspirin for at least 4 weeks; then discontinue clopidogrel and continue aspirin indefinitely thereafter. In patients with history of neck irradiation, some experts recommend continuing clopidogrel plus aspirin indefinitely (ASA/ACCF/AHA [Brott 2011]; Brott 2010; Jim 2021a).
Transcarotid approach:
Initial:
Initiation ≥72 hours before procedure: Oral: 75 mg once daily in combination with aspirin (Kwolek 2015).
Initiation <72 hours before procedure: Oral: 450 mg once at least 4 hours before procedure in combination with aspirin (Kwolek 2015).
Maintenance: Oral: 75 mg once daily in combination with aspirin for at least 4 weeks; then discontinue clopidogrel and continue aspirin indefinitely thereafter. In patients with history of neck irradiation, some experts recommend continuing clopidogrel plus aspirin indefinitely (Brott 2010; Jim 2021b; Kwolek 2015).
Coronary artery bypass graft surgery (off-label use):
Aspirin-allergic or aspirin-intolerant patients: Oral: 75 mg once daily; continue indefinitely (AHA [Kulik 2015]). Some experts recommend a loading dose of 300 mg administered 6 hours after surgery, followed by 75 mg once daily (Levin 2021).
Following off-pump coronary artery bypass graft surgery: Oral: 75 mg once daily in combination with aspirin for 1 year, then discontinue clopidogrel and continue aspirin indefinitely (AHA [Kulik 2015]; Deo 2013; Mannacio 2012).
Patients with acute coronary syndrome followed by coronary artery bypass graft surgery: Oral: 75 mg once daily in combination with aspirin for 1 year, then discontinue clopidogrel and continue aspirin indefinitely (AHA [Kulik 2015]). Some experts do not use clopidogrel postoperatively in these patients (Aranki 2020).
Isch emic stroke/transient ischemic attack
Note: In patients who receive IV thrombolytic, antiplatelet therapy is generally delayed for ≥24 hours, but administered as soon as possible thereafter (AHA/ASA [Powers 2019]; Filho 2022).
Intracranial atherosclerosis (50% to 99% stenosis of a major intracranial artery), secondary prevention:
Note: Aspirin is recommended for all patients; may consider clopidogrel (in combination with aspirin) for short-term use in patients with recent stroke or transient ischemic attack (TIA) (within 30 days) (AHA/ASA [Kleindorfer 2021]). For long-term stroke prevention, indefinite use of clopidogrel monotherapy is an alternative to aspirin (Turan 2021).
Oral: 75 mg once daily in combination with aspirin; duration of clopidogrel depends on degree of stenosis and severity of stroke or TIA. Some experts recommend a loading dose of 300 to 600 mg once, followed by 75 mg once daily (Turan 2021; Wang 2013; manufacturer's labeling).
Stenosis of 50% to 69% and high-risk transient ischemic attack (ABCD 2 score ≥4) or minor ischemic stroke (National Institutes of Health Stroke Scale score ≤5 ): Clopidogrel may be added to aspirin for 21 days; after 21 days, discontinue clopidogrel and continue aspirin indefinitely (Turan 2021).
Stenosis of 70% to 99%: Clopidogrel may be added to aspirin for up to 90 days; after 90 days, discontinue clopidogrel and continue aspirin indefinitely (AHA/ASA [Kleindorfer 2021]; Derdeyn 2014; Turan 2021).
Noncardioembolic ischemic stroke or transient ischemic attack, secondary prevention:
Note: Single-agent antiplatelet therapy is recommended for long-term secondary prevention. Aspirin, clopidogrel, or aspirin/ER dipyridamole are all reasonable options depending on patient-specific factors. Some experts, however, prefer clopidogrel or aspirin/ER dipyridamole (ACCP [Lansberg 2012]; AHA/ASA [Kleindorfer 2021]; Cucchiara 2022).
Oral: 75 mg once daily indefinitely (AHA/ASA [Kleindorfer 2021]).
Minor ischemic stroke (National Institutes of Health Stroke Scale score ≤5) or high-risk transient ischemic attack (ABCD2 score ≥4):
Note: Short-term use of clopidogrel in combination with aspirin may be considered in patients who meet these criteria. Initiate antiplatelet therapy as soon as possible and within 24 hours of stroke onset (AHA/ASA [Kleindorfer 2021]; AHA/ASA [Powers 2019]; Filho 2022; Johnston 2018; Wang 2013).
Oral: 300 to 600 mg once in combination with aspirin; followed by 75 mg once daily in combination with aspirin for 21 to 90 days (some experts recommend limiting to 21 days [AHA/ASA (Powers 2019); Filho 2022]), followed by single-agent antiplatelet therapy with aspirin, clopidogrel, or aspirin/ER dipyridamole and continue indefinitely. If clopidogrel is used, continue to administer 75 mg once daily (ACCP [Lansberg 2012]; AHA/ASA [Kleindorfer 2021]; AHA/ASA [Powers 2019]; Johnston 2018; Wang 2013).
Peripheral atherosclerotic disease (upper or lower extremity; with or without revascularization) : Oral: 75 mg once daily (ACCP [Alonso-Coello 2012]; AHA/ACC [Gerhard-Herman 2017]; CAPRIE 1996).
Stable ischemic heart disease (alternative agent) (off-label use):
Note: Aspirin is preferred; clopidogrel is an alternative for patients who have a history of GI bleeding or are allergic to aspirin (ACCF/AHA [Fihn 2012]).
Oral: 75 mg once daily (ACCF/AHA [Fihn 2012]; ACCP [Vandvik 2012]; CAPRIE 1996).
Transcatheter aortic valve replacement, thromboprophylaxis (off-label use):
Note: Refer to institutional policies and procedures on use of antiplatelet therapy for patients who require therapeutic anticoagulation for a different indication.
Oral: 300 mg once prior to valve implantation in combination with aspirin, followed by 75 mg once daily; may be used in combination with aspirin for 3 to 6 months depending on the type of valve implanted (ACC [Otto 2017]; ACC/AHA [Otto 2021]; Kalich 2018). To minimize risk of bleeding complications, may give aspirin or clopidogrel alone and reserve dual antiplatelet therapy during the first 3 to 6 months for patients at high risk of a thrombotic event; for either strategy, continue aspirin indefinitely after the initial 3 to 6 months of therapy (Brouwer 2020; Kuno 2019).
Transcatheter mitral valve repair with MitraClip device, thromboprophylaxis (off-label use):
Note: Patients are generally treated with antithrombotic therapy (antiplatelet or anticoagulant if there is a concurrent indication) for at least 6 months following the procedure (Stone 2018).
Oral:
Loading dose: 300 mg once immediately following MitraClip insertion or within 24 hours prior to the procedure; may use as monotherapy or in combination with aspirin (Stone 2018).
Maintenance: 75 mg once daily for at least 6 months; may use as monotherapy or in combination with aspirin (Stone 2018).
Transitioning between P2Y12 inhibitors: Note: This provides general guidance on transitioning between P2Y12 inhibitors.
Transitioning from another P2Y12 inhibitor to clopidogrel:
Transitioning from prasugrel:
Patient received prasugrel for ≤5 days: Give a clopidogrel 300 mg loading dose 24 hours after the last dose of prasugrel, followed by 75 mg once daily; some experts do not administer a loading dose (Lincoff 2020).
Patient received prasugrel for >5 days: Give clopidogrel 75 mg once daily, starting 24 hours after the last dose of prasugrel (Kerneis 2013; Lincoff 2020).
Transitioning from ticagrelor: Give a clopidogrel 600 mg loading dose 12 to 24 hours after the last dose of ticagrelor, followed by 75 mg once daily (Angiolillo 2017; Franchi 2018; Lincoff 2020).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Patients with chronic kidney disease, especially those with end-stage kidney disease (ESKD), have a higher incidence of high on-treatment platelet reactivity when treated with clopidogrel (Muller 2012; Tanios 2014; Wu 2019). Monitor for thrombotic complications and consider measuring platelet reactivity in patients at high risk for thrombotic events (Sibbing 2019). Patients with ESKD are also at increased risk for bleeding, with or without antiplatelet therapy (Huang 2014; Tanios 2014); monitor closely.
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Deray 1998).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (highly protein bound): No supplemental dose or dosage adjustment necessary (expert opinion).
Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound): No dosage adjustment necessary (expert opinion).
CRRT: No dosage adjustment necessary (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).
No dosage adjustment necessary.
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
Yes
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
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020839s072lbl.pdf#page=24, must be dispensed with this medication.
Oral: May be administered without regard to food.
Administer without regard to meals.
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Reduction of atherothrombotic events (myocardial infarction [MI], stroke, and vascular deaths) in patients with recent MI, stroke, or established peripheral arterial disease (FDA approved in adults); reduction of atherothrombotic events in patients with non-ST-segment elevation acute coronary syndrome (unstable angina and non-ST-elevation MI) managed medically and with coronary revascularization (FDA approved in adults); reduction of death rate and atherothrombotic events in patients with acute ST-elevation MI (STEMI) managed medically (FDA approved in adults).
Plavix may be confused with Elavil, Paxil, Pradax (Canada), Pradaxa
Clopidogrel may cause minor hemorrhage or major hemorrhage. In the CURE trial, clopidogrel was associated with significantly more major bleeding, defined as disabling bleeding, intraocular bleeding leading to the loss of vision, or bleeding necessitating the need for a transfusion of at least 2 units of blood (Ref). Bleeding should be suspected if patient becomes hypotensive, 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 clopidogrel loading dose or 2 hours of the maintenance dose may be less effective. Other studies suggest that platelet transfusions are ineffective in reversing antiplatelet effects (Ref). May result in temporary or permanent discontinuation (Ref).
Mechanism: Related to the pharmacologic action. Clopidogrel irreversibly binds to the P2Y12 receptor on platelets, which inhibits adenosine diphosphate (ADP)-mediated platelet activation and aggregation (Ref).
Onset: Varied; one study found that clopidogrel was associated with increased risk of major bleeding during all time intervals assessed (0 to 6 months, 7 to 12 months, and 13 to 18 months) (Ref). Other studies suggest that bleeding risk increases after 21 days of therapy (Ref).
Risk factors:
• Age ≥75 years (Ref)
• Concurrent medications that increase the risk of bleeding (eg, aspirin, direct oral anticoagulants, nonsteroidal anti-inflammatory drugs, warfarin) (Ref)
• Higher doses of concurrent aspirin (≥200 mg/day) (Ref)
• Active peptic ulcer disease (Ref)
• Recent trauma or surgery (Ref)
• Recent or recurrent GI bleed (Ref)
• Use >6 months (Ref)
Clopidogrel hypersensitivity may present as immediate (eg, angioedema, urticaria) and delayed reactions. Delayed hypersensitivity reactions range from the more common pruritic maculopapular rash to rare severe cutaneous adverse reactions including drug reaction with eosinophilia and systemic symptoms and acute generalized exanthematous pustulosis (Ref). Drug discontinuation due to a pruritic rash may occur in up to 1.5% of patients (Ref).
Mechanism: Immediate hypersensitivity reactions: Non–dose-related; immunologic (ie, IgE-mediated) (Ref). Delayed hypersensitivity reactions: Non–dose-related; immunologic (ie, likely involving a T-cell mediated drug-specific immune response) (Ref).
Onset: Rapid to intermediate; mean onset of maculopapular, pruritic rash is 6 ± 2 days after initiation (Ref).
Risk factors:
• Cross-reactivity: Because of structural similarities, cross-reactivity has been reported among the thienopyridines (clopidogrel, prasugrel, ticlopidine) (Ref)
Cases of thrombotic thrombocytopenic purpura (TTP) associated with clopidogrel use have been reported and some have resulted in fatalities (Ref); however, incidence is rare (0.0001%) (Ref). Early signs of TTP are typically skin reactions or neurologic changes (eg, seizure, coma, stroke, headache, blurred vision) (Ref). TTP is typically characterized by thrombocytopenia, hemolytic anemia, kidney failure, and fever (Ref).
Mechanism: Non–dose-related; immunologic or idiosyncratic. The mechanism for TTP is unknown but likely involves microvascular endothelial cell damage (Ref). Decreased ADAMTS-13 activity has been noted; although, some patients have normal ADAMTS13 activity, suggesting that the mechanism may not be immunologic (Ref). Another proposed mechanism is that clopidogrel may act as a hapten in patients with preexisting autoimmune disease (Ref).
Onset: Intermediate; usually occurs within 2 weeks of initiation of therapy (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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%: Hematologic & oncologic: Major hemorrhage (≤4%; major hemorrhage, life-threatening: ≤2%) (table 1) , minor hemorrhage (4% to 5%) (table 2)
Drug (Clopidogrel [+ Aspirin]) |
Placebo (+ Aspirin) |
Number of Patients (Clopidogrel [+ Aspirin]) |
Number of Patients (Placebo [+ Aspirin]) |
Comments |
---|---|---|---|---|
4% |
3% |
6,259 |
6,303 |
N/A |
2% |
2% |
6,259 |
6,303 |
Life-threatening |
0.6% |
0.5% |
22,961 |
22,891 |
N/A |
Drug (Clopidogrel [+ Aspirin]) |
Placebo (+ Aspirin) |
Number of Patients (Clopidogrel [+ Aspirin]) |
Number of Patients (Placebo [+ Aspirin]) |
---|---|---|---|
5% |
2% |
6,259 |
6,303 |
4% |
3% |
22,961 |
22,891 |
<1%:
Cardiovascular: Hemorrhagic stroke
Nervous system: Intracranial hemorrhage
Postmarketing:
Cardiovascular: Hypotension, vasculitis (Shetty 2013)
Dermatologic: Acute generalized exanthematous pustulosis (Ulman 2014), bullous rash, eczema, erythema multiforme, erythematous rash (Cheema 2011), exfoliative dermatitis, lichen planus, lichenoid eruption (Dogra 2003), maculopapular rash (Cheema 2011), pruritus (Cheema 2011), pustular psoriasis (Meissner 2006), Stevens-Johnson syndrome (Báez-Ferrer 2019), toxic epidermal necrolysis, urticaria (Cheema 2011)
Endocrine & metabolic: Insulin autoimmune syndrome (Rajpal 2017)
Gastrointestinal: Ageusia (Cave 2008), colitis (including ulcerative colitis or lymphocytic colitis), diarrhea, duodenal ulcer (Ebi 2018), gastric ulcer, pancreatitis, stomatitis
Hematologic & oncologic: Acquired blood coagulation disorder (hemophilia A), agranulocytosis, aplastic anemia (Uz 2010), pancytopenia (Matthews 2009), thrombotic thrombocytopenic purpura (Zakarijia 2009)
Hepatic: Acute hepatic failure (Monteiro 2011), hepatitis (noninfectious) (Pisapia 2015)
Hypersensitivity: Angioedema (Cheema 2011), nonimmune anaphylaxis, serum sickness (Phillips 2003)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Inagaki 2020)
Nervous system: Confusion, hallucination (Osuagwu 2016), headache
Neuromuscular & skeletal: Arthralgia (Coulter 2012), arthritis (Garg 2000), myalgia
Renal: Increased serum creatinine
Respiratory: Bronchospasm, eosinophilic pneumonitis (Inagaki 2020), interstitial pneumonitis (Tomoda 2021)
Miscellaneous: Fever (Cheema 2011)
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.
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 kidney impairment.
Special populations:
• CYP2C19 poor metabolizers: Routine platelet function testing or genetic testing for CYP2C19 polymorphisms is not recommended (ACC/AHA [Levine 2016]; Scott 2013; Sibbing 2019).
• 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. If antiplatelet agents are discontinued, they 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 generally not be discontinued. Dual antiplatelet therapy (DAPT) should generally 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 DAPT); 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 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, DAPT may be continued. In patients with stents undergoing surgery that requires discontinuation of the P2Y12 inhibitor, 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 (ACCF/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 acute coronary syndrome event was ongoing at the time of placement (ACC/AHA [Levine 2016]; AHA/ACC/SCAI/ACS/ADA [Grines 2007]).
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)
Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
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
Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Risk D: Consider therapy modification
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
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Berotralstat: BCRP/ABCG2 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with BCRP inhibitors. 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. 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
Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Risk D: Consider therapy modification
Cobicistat: May decrease serum concentrations of the active metabolite(s) of Clopidogrel. 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. Management: Consider alternatives to this combination when possible. If combined, monitor for increased clopidogrel effects and toxicities (eg, bleeding) if clopidogrel is combined with a strong CYP2C19 inducer. Risk D: Consider therapy modification
CYP2C19 Inhibitors (Moderate): May decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy
CYP2C19 Inhibitors (Strong): May decrease serum concentrations of the active metabolite(s) of Clopidogrel. Management: Consider alternatives to this combination whenever possible. If such a combination must be used, monitor patients closely for evidence of a diminished response to clopidogrel. Risk D: Consider therapy modification
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
Dabrafenib: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Dabrafenib. Risk C: Monitor therapy
Dasabuvir: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Dasabuvir. Risk C: Monitor therapy
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. 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
Desloratadine: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Desloratadine. 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
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Enzalutamide: CYP2C8 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Enzalutamide. CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Enzalutamide. Risk C: Monitor therapy
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. Risk X: Avoid combination
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
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
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
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
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
Icosapent Ethyl: May enhance the antiplatelet 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
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic 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: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir. Specifically, the concentrations of the dasabuvir component may be increased. 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. Risk X: Avoid combination
Ozanimod: CYP2C8 Inhibitors (Moderate) may increase serum concentrations of the active metabolite(s) of Ozanimod. Risk C: Monitor therapy
PACLitaxel (Conventional): CYP2C8 Inhibitors (Moderate) may increase the serum concentration of PACLitaxel (Conventional). Risk C: Monitor therapy
PACLitaxel (Protein Bound): CYP2C8 Inhibitors (Moderate) 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: CYP2C8 Inhibitors (Moderate) 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
Ritonavir: May diminish the antiplatelet effect of Clopidogrel. Ritonavir may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Risk C: Monitor therapy
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. Management: Reduce the selexipag dose to once daily when combined with moderate CYP2C8 inhibitors. Revert back to twice daily selexipag dosing upon stopping the moderate CYP2C8 inhibitor. Risk D: Consider therapy modification
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Sibutramine: CYP2B6 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Sibutramine. CYP2B6 Inhibitors (Weak) may increase the serum concentration of Sibutramine. Risk C: Monitor therapy
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
Treprostinil: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Treprostinil. Risk C: Monitor therapy
Tucatinib: CYP2C8 Inhibitors (Moderate) may increase the serum concentration of Tucatinib. Risk C: Monitor therapy
Ubrogepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and second dose (at least 2 hours later if needed) of 50 mg when used with a BCRP inhibitor. Risk D: Consider therapy modification
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
Vonoprazan: May diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
Warfarin: Clopidogrel may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
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).
Avoid or minimize the consumption of grapefruit juice (Holmberg 2013).
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]).
Signs of bleeding; hemoglobin and hematocrit periodically. Monitor mean inhibition of platelet aggregation: Goal of 30% to 50% inhibition (similar to adults receiving 75 mg/day). For unstable angina/non-ST-elevation myocardial infarction in adults, platelet function testing has been used to determine platelet inhibitory response if results of testing may alter management (Wright 2011).
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).
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%)
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.
5 mg/mL Oral Suspension
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.
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
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