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Clopidogrel

Grade

Thromboprophylaxis

Initial Dosing

  • Loading: A single loading dose of 4-10 mg/kg, PO 

Subsequent Dosing

  • Maintenance: Follow a loading dose with 1-4 mg/kg, PO, q24h.

Additional Medications

  • Thromboprophylaxis: Clopidogrel may be employed alongside other thromboprophylaxis agents (other antiplatelet or anticoagulant agents such as Aspirin and Heparin), although supporting evidence remains limited.

  • Comorbidities: Treatment for combidities are patient and ciondition specific. Underlying conditions such as IMHA will require approptre diagnosis, monitoring and treatment protocols. 

  • Critical Care: Many patients will require other additional support medications such as analgesics, antimicrobials and gastroprotectants.

Alternative Medications and Protocols

  • Aspirin: Clopidogrel is currently preferred to aspirin for thromboprophylaxis (Swann et al., 2019). See our Acetylssalicilic Acid (Aspirin) monograph for thromboprophylaxxis advice using this agent.

Patient Support

  • Therapeutic Monitoring:  Monitor for thromboprophylaxis requirements, i.e. regular physical assessment and review of haematology and bleeding times. 

Suitability

Our suitability recommendations are extrapolations derived from human and animal data (Blais et al., 2019; Borgarelli et al., 2017; Brainard et al., 2010; Mellett et al., 2011; Morassi et al., 2016; Swann et al., 2019; Thames et al., 2017; Thomason et al., 2020, 2016; Whittemore et al., 2019).


  • ATE: Clopidogrel appears safe and effective for preventing arterial thrombosis in dogs and cats. 

  • IMHA: Thromboprophylaxis is recommended in all dogs with immune-mediated hemolytic anaemia (IMHA) unless severe thrombocytopenia is present (i.e., a platelet count <30,000/µL) (Swann et al., 2019).

Patient Preparation

  • Physical Assessment: Ensure patients are free from obvious complications (described below). Patients require suitable clinical assessment and appropriate nursing care, and environmental provisions.

Formulations

  • Clopidogrel/Plavix: 18.75 mg, 75 mg, 300 mg Tablets.



Therapeutics

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Sole Use

  • Evidence supporting sole use vs multimodal use alongside additional agents is poor, and no strong recommendations can be made. 

Multimodal Use

  • Clopidogrel may be employed alongside other thromboprophylaxis agents (other antiplatelet or anticoagulant agents such as Aspirin and Heparin), although supporting evidence remains limited.

Treatment Goals

  • Prevention of thrombosis where there is a known risk of bleeding.

  • Treatment of animals with thrombosis.

Treatment Endpoints

  • In patients with thrombosis whose underlying cause has resolved, indefinite treatment with anticoagulant medication is not recommended.

  • Anticoagulant medication can be continued indefinitely if the underlying cause is unknown or untreatable.

Therapeutic Monitoring

Monitoring recommendations are extrapolations derived from human and animal data (Blais et al., 2019; Goggs et al., 2019; Swann et al., 2019).


  • Assess the risk of bleeding. Consider the patient's age, gender, and comorbidities, such as impaired renal function. 

  • Regular haematological assessment is considered beneficial. 

  • Monitoring of bleeding time is generally not required for antiplatelet medications; however, if bleeding is present, bleeding time is helpful to determine transfusion requirement or medicine discontinuation.

Efficacy Profile

Efficacy comments are extrapolations derived from human and animal data (Blais et al., 2019; Goggs et al., 2019; Swann et al., 2019).

  • There is insufficient evidence to make firm recommendations regarding clopidogrel versus aspirin in dogs, and some authors suggest that clopidogrel may be more effective than aspirin in dogs at risk for ATE.

Adverse Effects Profile

Adverse effects comments are extrapolations derived from human and animal data (Blais et al., 2019; Goggs et al., 2019; Swann et al., 2019)


  • Vomiting and bleeding (Upper gastrointestinal bleeding because of chronic gastritis, ecchymosis, hematuria, and epistaxis) are the most likely adverse effects.

Contraindications

Contraindication comments are extrapolations derived from human and animal data (Blais et al., 2019; Goggs et al., 2019; Swann et al., 2019; Whittemore et al., 2019).


  • Coagulopathies and Bleeding Disorders: Do not use during coagulopathies and bleeding disorders, e.g. Von Willebrand's disease, concurrent gastrointestinal tract ulceration or known hypersensitivity to the agent or excipients. 

  • Recent Blood Loss: Avoid use if clinically significant bleeding is present or has recently occurred.

  • Thrombocytopenia: Avoid use in significant thrombocytopenia

  • Hepatopathy: Avoid use in severe liver disease.

  • Nephropathy: Avoid use in severe kidney disease.

Pregnancy

Pregnancy recommendations are extrapolations derived from human and animal data (Bell et al., 2011; M et al., 2021).

  • The effects are unknown. Clopidogrel is not recommended during pregnancy, but an appropriate risk-benefit analysis supports its use in life-threatening clinical settings.

Lactation

Lactation recommendations are extrapolations derived from human and animal data (Bell et al., 2011; M et al., 2021).

  • The effects are unknown. Clopidogrel is not recommended during lactation, but an appropriate risk-benefit analysis supports its use in life-threatening clinical settings.

Male Fertility

Male fertility recommendations are extrapolations derived from human and animal data. Safety data is yet to be located. Adverse fertility effects are not described in the human and animal studies analysed.

  • The effects are unknown. Clopidogrel is not recommended during periods of active male breeding, but an appropriate risk-benefit analysis supports its use in life-threatening clinical settings.

Female Fertility

Female fertility recommendations are extrapolations derived from human and animal data. Safety data has yet to be located. Adverse fertility effects are not described in the human and animal studies analysed.

  • The effects are unknown. Clopidogrel is not recommended during periods of active female breeding, but an appropriate risk-benefit analysis supports its use in life-threatening clinical settings.

Interactions

Interaction comments are extrapolations derived from human and animal data (AlSawy et al., 2023; Dalal et al., 2023; Kalyanasundaram et al., 2011; Lee et al., 2012; Thomason et al., 2016).

  • Other coagulation inhibitors and antiplatelet medicines:  Concurrent use of medications, such as Aspirin, Melagatran and Rivaroxaban, increases the risk of bleeding; simultaneous use in humans is accepted.

  • Non-steroidal anti-inflammatory drugs NSAIDs: Concurrent use increases bleeding risk. Typically, stomach and intestinal bleeding in humans.

  • CYP2C19 Inhibitors: Avoid concurrent use of these medications, including Omeprazole, Esomeprazole, Cimetidine, Fluconazole, Ketoconazole, Voriconazole, Etravirine, Felbamate, Fluoxetine, Fluvoxamine and Ticlopidine.

  • P450 Substrates: High-dose Clopidogrel may also inhibit P450 (2C9), interfering with the metabolism of medicines including Phenytoin, Tamoxifen, Torasemide, Fluvastatin and some NSAIDs.

Alternative Products 

  • In general practice, acetylsalicylic acid (Aspirin) is the apparent alternative to Clopidogrel. New antiplatelet agents are becoming available (e.g. Abciximab, Apixaban, Prasugrel and Ticagrelor).

Alternative Protocols

  • Evidence-based recommendations concerning comparative protocols are not yet available for most antithrombotic drugs evaluated, either because of the wide range of dosage reported (e.g., aspirin) or the lack of evidence in the current literature (e.g.clopidogrel) (Blais et al., 2019).

Evidence

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  1. AlSawy, N.S., ElKady, E.F., Mostafa, E.A., 2023. AGREE and ESA for Greenness Assessment of a Novel Validated RP-HPLC Method for Simultaneous Determination of Aspirin, Warfarin and Clopidogrel in Rat Plasma: Application to Pharmacokinetic Study of the Possible Interaction between the Three Drugs. J Chromatogr Sci bmad078. https://doi.org/10.1093/chromsci/bmad078

  2. Barnes, G.D., Stanislawski, M.A., Liu, W., Barón, A.E., Armstrong, E.J., Ho, P.M., Klein, A., Maddox, T.M., Nallamothu, B.K., Rumsfeld, J.S., Tsai, T.T., Bradley, S.M., 2016. Use of Contraindicated Antiplatelet Medications in the Setting of Percutaneous Coronary Intervention: Insights from the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program. Circ Cardiovasc Qual Outcomes 9, 406–413. https://doi.org/10.1161/CIRCOUTCOMES.115.002043

  3. Bell, A.D., Roussin, A., Cartier, R., Chan, W.S., Douketis, J.D., Gupta, A., Kraw, M.E., Lindsay, T.F., Love, M.P., Pannu, N., Rabasa-Lhoret, R., Shuaib, A., Teal, P., Théroux, P., Turpie, A.G.G., Welsh, R.C., Tanguay, J.-F., 2011. The Use of Antiplatelet Therapy in the Outpatient Setting: Canadian Cardiovascular Society Guidelines. Canadian Journal of Cardiology 27, S1–S59. https://doi.org/10.1016/j.cjca.2010.12.015

  4. Blais, M.-C., Bianco, D., Goggs, R., Lynch, A.M., Palmer, L., Ralph, A., Sharp, C.R., 2019. Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 3—Defining antithrombotic protocols. Journal of Veterinary Emergency and Critical Care 29, 60–74. https://doi.org/10.1111/vec.12795

  5. Borgarelli, M., Lanz, O., Pavlisko, N., Abbott, J.A., Menciotti, G., Aherne, M., Lahmers, S.M., Lahmers, K.K., Gammie, J.S., 2017. Mitral valve repair in dogs using an ePTFE chordal implantation device: a pilot study. J Vet Cardiol 19, 256–267. https://doi.org/10.1016/j.jvc.2017.03.002

  6. Brainard, B.M., Buriko, Y., Good, J., Ralph, A.G., Rozanski, E.A., 2019. Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 5-Discontinuation of anticoagulant therapy in small animals. J Vet Emerg Crit Care (San Antonio) 29, 88–97. https://doi.org/10.1111/vec.12796

  7. Brainard, B.M., Kleine, S.A., Papich, M.G., Budsberg, S.C., 2010. Pharmacodynamic and pharmacokinetic evaluation of clopidogrel and the carboxylic acid metabolite SR 26334 in healthy dogs. Am J Vet Res 71, 822–830. https://doi.org/10.2460/ajvr.71.7.822

  8. Dalal, J., Dutta, A.L., Hiremath, J., Iyengar, S.S., Mohan, J.C., Ooman, A., Goswami, B., Shenoy, K.T., 2023. Cardiovascular Compatibility of Proton Pump Inhibitors: Practice Recommendations. Cardiol Ther. https://doi.org/10.1007/s40119-023-00338-1

  9. Goggs, R., Bacek, L., Bianco, D., Koenigshof, A., Li, R.H.L., 2019. Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE): Domain 2—Defining rational therapeutic usage. Journal of Veterinary Emergency and Critical Care 29, 49–59. https://doi.org/10.1111/vec.12791

  10. Kalyanasundaram, A., Lincoff, A.M., Medscape, 2011. Managing adverse effects and drug-drug interactions of antiplatelet agents. Nat Rev Cardiol 8, 592–600. https://doi.org/10.1038/nrcardio.2011.128

  11. Lee, J.H., Shin, Y.-J., Oh, J.-H., Lee, Y.-J., 2012. Pharmacokinetic interactions of clopidogrel with quercetin, telmisartan, and cyclosporine A in rats and dogs. Arch Pharm Res 35, 1831–1837. https://doi.org/10.1007/s12272-012-1017-7

  12. Mellett, A. m., Nakamura, R. k., Bianco, D., 2011. A Prospective Study of Clopidogrel Therapy in Dogs with Primary Immune-Mediated Hemolytic Anemia. Journal of Veterinary Internal Medicine 25, 71–75. https://doi.org/10.1111/j.1939-1676.2010.0656.x

  13. Morassi, A., Bianco, D., Park, E., Nakamura, R.K., White, G.A., 2016. Evaluation of the safety and tolerability of rivaroxaban in dogs with presumed primary immune-mediated hemolytic anemia. J Vet Emerg Crit Care (San Antonio) 26, 488–494. https://doi.org/10.1111/vec.12480

  14. Nana, N., H, M., S, M., Zx, L., E, A., C, N.-P., 2021. Antiplatelet therapy in pregnancy: A systematic review. Pharmacological research 168. https://doi.org/10.1016/j.phrs.2021.105547

  15. Saati, S., Abrams‐Ogg, A.C.G., Blois, S.L., Wood, R.D., 2018. Comparison of Multiplate, Platelet Function Analyzer‐200, and Plateletworks in Healthy Dogs Treated with Aspirin and Clopidogrel. J Vet Intern Med 32, 111–118. https://doi.org/10.1111/jvim.14886

  16. Skillman, K.L., Caruthers, R.L., Johnson, C.E., 2010. Stability of an extemporaneously prepared clopidogrel oral suspension. Am J Health Syst Pharm 67, 559–561. https://doi.org/10.2146/ajhp090163

  17. Swann, J.W., Garden, O.A., Fellman, C.L., Glanemann, B., Goggs, R., LeVine, D.N., Mackin, A.J., Whitley, N.T., 2019. ACVIM consensus statement on the treatment of immune-mediated hemolytic anemia in dogs. J Vet Intern Med 33, 1141–1172. https://doi.org/10.1111/jvim.15463

  18. Thames, B.E., Lovvorn, J., Papich, M.G., Wills, R., Archer, T., Mackin, A., Thomason, J., 2017. The effects of clopidogrel and omeprazole on platelet function in normal dogs. J Vet Pharmacol Ther 40, 130–139. https://doi.org/10.1111/jvp.12340

  19. Thomason, J., Lunsford, K., Mackin, A., 2016. Anti-platelet therapy in small animal medicine. Journal of Veterinary Pharmacology and Therapeutics 39, 318–335. https://doi.org/10.1111/jvp.12301

  20. Thomason, J., Mooney, A.P., Price, J.M., Whittemore, J.C., 2020. Effects of clopidogrel and prednisone on platelet function in healthy dogs. J Vet Intern Med 34, 1198–1205. https://doi.org/10.1111/jvim.15759

  21. Whittemore, J.C., Mooney, A.P., Price, J.M., Thomason, J., 2019. Clinical, clinicopathologic, and gastrointestinal changes from administration of clopidogrel, prednisone, or combination in healthy dogs: A double‐blind randomized trial. J Vet Intern Med 33, 2618–2627. https://doi.org/10.1111/jvim.15630

  22. Yankin, I., Carver, A.M., Koenigshof, A.M., 2021. The use of impedance aggregometry to evaluate platelet function after the administration of DDAVP in healthy dogs treated with aspirin or clopidogrel. American Journal of Veterinary Research 82, 823–828. https://doi.org/10.2460/ajvr.82.10.823

  23. Yi, Y.Y., Shin, H.J., Choi, S.G., Kang, J.W., Song, H.-J., Kim, S.K., Kim, D.W., 2020. Preventive Effects of Neuroprotective Agents in a Neonatal Rat of Photothrombotic Stroke Model. Int J Mol Sci 21, 3703. https://doi.org/10.3390/ijms21103703

Datasheets

Monograph Details

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