Abstract
Clopidogrel is a widely used antiplatelet agent, particularly after coronary stent implantation. About 1% of patients have allergic or hematologic adverse reactions to clopidogrel. This has important therapeutic implications, as premature discontinuation of clopidogrel is the strongest risk factor for stent thrombosis. Clopidogrel allergy most commonly manifests as a rash. It is important to distinguish this from other causes of rash occurring in patients who have had a recent coronary stent. Although antihistamines and short-term oral corticosteroids are effective in treating most clopidogrel hypersensitivity reactions, some persistent reactions may require discontinuation of clopidogrel. When discontinuation of clopidogrel is required, substitution with an alternative thienopyridine such as ticlopidine traditionally has been performed. However, a recent study suggests that there may be as high as a 27% risk of recurrence of non-life-threatening allergic reactions in such patients, which are usually similar to the allergic reactions that occurred with clopidogrel. No data are available regarding the frequency of cross-reactivity to prasugrel and ticagrelor; these may be potential therapeutic options in some patients.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance
Plavix [package insert]. Bridgewater, NJ: Bristol-Myers Squibb/Sanofi-Aventis; 2010.
Grines CL, Bonow RO, Casey DE Jr, et al.: Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. J Am Coll Cardiol 2007, 49:734–739.
A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996, 348:1329–1339.
Bertrand ME, Legrand V, Boland J, et al.: Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study. Circulation 1998, 98:1597–1603.
Sharis PJ, Cannon CP, Loscalzo J: The antiplatelet effects of ticlopidine and clopidogrel. Ann Intern Med 1998, 129:394–405.
Farid NA, Payne CD, Small DS, et al.: Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther 2007, 81:735–741.
Jakubowski JA, Winters KJ, Naganuma H, Wallentin L: Prasugrel: a novel thienopyridine antiplatelet agent. A review of preclinical and clinical studies and the mechanistic basis for its distinct antiplatelet profile. Cardiovasc Drug Rev 2007, 25:357–374.
Doogue MP, Begg EJ, Bridgman P: Clopidogrel hypersensitivity syndrome with rash, fever, and neutropenia. Mayo Clin Proc 2005, 80:1368–1370.
von Tiehl KF, Price MJ, Valencia R, et al.: Clopidogrel desensitization after drug-eluting stent placement. J Am Coll Cardiol 2007, 50:2039–2043.
• Lokhandwala JO, Best PJM, Butterfield JH, et al.: Frequency of allergic or hematologic adverse reactions to ticlopidine among patients with allergic or hematologic adverse reactions to clopidogrel. Circ Cardiovasc Intervent 2009, 2:348–351. This is the only study to evaluate the frequency and severity of allergic cross-reactivity between clopidogrel and ticlopidine with important therapeutic implications.
Chinnakotla S, Leone JP, Fidler ME, et al.: Clopidogrel-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in a kidney/pancreas transplant recipient. Transplantation 2000, 70:550–552.
Depta JP, Pichler WJ: Cross-reactivity with drugs at the T cell level. Curr Opin Allergy Clin Immunol 2003, 3:261–267.
Ray WA: Population-based studies of adverse drug effects. N Engl J Med 2003, 349:1592–1594.
Camara MG, Almeda FQ: Clopidogrel (Plavix) desensitization: a case series. Catheter Cardiovasc Interv 2005, 65:525–527.
Makkar K, Wilensky RL, Julien MB, et al.: Rash with both clopidogrel and ticlopidine in two patients following percutaneous coronary intervention with drug-eluting stents. Ann Pharmacother 2006, 40:1204–1207.
Rotmensch HH, Vlasses PH, Ferguson RK: Resolution of captopril-induced rash after substitution of enalapril. Pharmacotherapy 1983, 3:131–133.
Vigo PG, MacDowell AL, Wedner HJ: Successful desensitization with clopidogrel after a positive skin test [abstract 44]. Ann Allergy Asthma Immunol 2005, 94:132–133.
Campbell K, Mallya R, Jaffrani W, et al.: Treatment of clopidogrel hypersensitivity without drug interruption. Circulation 2008, 118(Suppl):891S–892S.
Morrow DA, Wiviott SD, White HD, et al.: Effect of the novel thienopyridine prasugrel compared with clopidogrel on spontaneous and procedural myocardial infarction in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38: an application of the classification system from the universal definition of myocardial infarction. Circulation 2009, 119:2758–2764.
Yoon Y, Shim WH, Lee DH, et al.: Usefulness of cilostazol versus ticlopidine in coronary artery stenting. Am J Cardiol 1999, 84:1375–1380.
Amsallem E, Kasparian C, Haddour G, et al.: Phosphodiesterase III inhibitors for heart failure. Cochrane Database Syst Rev 2005, 1:CD002230.
Leon MB, Baim DS, Popma JJ, et al.: A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. N Engl J Med 1998, 339:1665–1671.
Schomig A, Neumann FJ, Kastrati A, et al.: A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med 1996, 334:1084–1089.
Walker NE, Fasano MB, Horwitz PA: Desensitization for the management of clopidogrel hypersensitivity: initial clinical experience. J Invasive Cardiol 2006, 18:341–344.
• Fajt M, Petrov A: Clopidogrel hypersensitivity: a novel multi-day outpatient oral desensitization regimen. Ann Pharmacother 2010, 44:11–18. This is a recent article studying a low-cost desensitization option.
Lee-Wong M, Gadhvi D, Resnick D: Clopidogrel desensitization. Ann Allergy Asthma Immunol 2006, 96:756–757.
Acknowledgments
This publication was made possible by grant no. 1 KL2 RR024151 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov. Information on Reengineering the Clinical Research Enterprise can be obtained from http://www.nihroadmap.nih.gov.
Disclosure
Dr. Berger has served as a consultant for AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company/Daiichi-Sankyo, and Ortho-McNeil; has received research funding for Geisinger Clinic from ThromboVision, Helena Chemical Co., Accumetrics, AstraZeneca, Haemoscope Corp., The Medicines Company, Corgenix Medical Corp., and Eli Lilly and Copmany/Daiichi-Sankyo; and owns equity in Lumen. Drs. Lokhandwala, Best, and Henry reported no potential conflicts of interest relevant to this article.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lokhandwala, J., Best, P.J.M., Henry, Y. et al. Allergic Reactions to Clopidogrel and Cross-Reactivity to Other Agents. Curr Allergy Asthma Rep 11, 52–57 (2011). https://doi.org/10.1007/s11882-010-0152-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11882-010-0152-9