Hypersensitivity reactions to clopidogrel
- John R Cohn, MD
John R Cohn, MD
- Professor of Medicine and Pediatrics
- Thomas Jefferson University
- Michael P Savage, MD
Michael P Savage, MD
- Ralph J Roberts Professor of Cardiology
- Thomas Jefferson University
- Section Editors
- N Franklin Adkinson, Jr, MD
N Franklin Adkinson, Jr, MD
- Section Editor — Drug Allergy
- Professor of Medicine
- Johns Hopkins University School of Medicine
- Donald Cutlip, MD
Donald Cutlip, MD
- Section Editor — Interventional Cardiology
- Professor of Medicine
- Harvard Medical School
- Beth Israel Deaconess Medical Center
Clopidogrel is a thienopyridine drug that inhibits platelet aggregation by blocking the adenosine diphosphate P2Y12 receptor. The most frequent use of clopidogrel is to prevent potentially fatal thrombosis of newly implanted coronary stents. Accordingly, hypersensitivity reactions to clopidogrel have particular importance in this setting, since the timing typically coincides with the period of heightened vulnerability for stent thrombosis. The most common hypersensitivity reactions to clopidogrel are dermatologic eruptions, although severe systemic reactions can also occur.
The incidence and clinical manifestations of clopidogrel reactions are discussed here. Management options for dermatologic eruptions are also reviewed. Therapeutic use of clopidogrel in the management of atherosclerotic arterial disease is reviewed separately:To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Lokhandwala J, Best PJ, Henry Y, Berger PB. Allergic reactions to clopidogrel and cross-reactivity to other agents. Curr Allergy Asthma Rep 2011; 11:52.
- Cheema AN, Mohammad A, Hong T, et al. Characterization of clopidogrel hypersensitivity reactions and management with oral steroids without clopidogrel discontinuation. J Am Coll Cardiol 2011; 58:1445.
- CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996; 348:1329.
- Calogiuri GF, Al-Sowaidi S, Nettis E, et al. A joint allergist/cardiologist classification for thienopyridines hypersensitivity reactions based on their symptomatic patterns and its impact on the management strategies. Int J Cardiol 2016; 222:509.
- von Tiehl KF, Price MJ, Valencia R, et al. Clopidogrel desensitization after drug-eluting stent placement. J Am Coll Cardiol 2007; 50:2039.
- Campbell KL, Cohn JR, Fischman DL, et al. Management of clopidogrel hypersensitivity without drug interruption. Am J Cardiol 2011; 107:812.
- Khambekar SK, Kovac J, Gershlick AH. Clopidogrel induced urticarial rash in a patient with left main stem percutaneous coronary intervention: management issues. Heart 2004; 90:e14.
- Fischer TC, Worm M, Groneberg DA. Clopidogrel-associated angioedema. Am J Med 2003; 114:77.
- Campbell KL, Cohn JR, Savage MP. Clopidogrel hypersensitivity: clinical challenges and options for management. Expert Rev Clin Pharmacol 2010; 3:553.
- Ellerbroek JC, Cleveland MG. Clopidogrel-associated acute generalized exanthematous pustulosis. Cutis 2011; 87:181.
- Jeung YJ, Lee JY, Oh MJ, et al. Comparison of the causes and clinical features of drug rash with eosinophilia and systemic symptoms and stevens-johnson syndrome. Allergy Asthma Immunol Res 2010; 2:123.
- Doogue MP, Begg EJ, Bridgman P. Clopidogrel hypersensitivity syndrome with rash, fever, and neutropenia. Mayo Clin Proc 2005; 80:1368.
- Andres E, Perrin AE, Alt M, et al. Febrile pancytopenia associated with clopidogrel. Arch Intern Med 2001; 161:125.
- Meyer B, Staudinger T, Lechner K. Clopidogrel and aplastic anaemia. Lancet 2001; 357:1446.
- Trivier JM, Caron J, Mahieu M, et al. Fatal aplastic anaemia associated with clopidogrel. Lancet 2001; 357:446.
- Akcay A, Kanbay M, Agca E, et al. Neutropenia due to clopidogrel in a patient with end-stage renal disease. Ann Pharmacother 2004; 38:1538.
- McCarthy MW, Kockler DR. Clopidogrel-associated leukopenia. Ann Pharmacother 2003; 37:216.
- Phillips EJ, Knowles SR, Shear NH. Serum sickness-like reaction associated with clopidogrel. Br J Clin Pharmacol 2003; 56:583.
- Williams MF, Maloof JA 3rd. Resolution of clopidogrel-associated polyarthritis after conversion to prasugrel. Am J Health Syst Pharm 2014; 71:1097.
- Agrawal S, Harburger J, Stallings G, et al. Clopidogrel-Induced Recurrent Polyarthritis. J Investig Med High Impact Case Rep 2013; 1:2324709613500239.
- Kanadiya MK, Singhal S, Koshal VB. Prasugrel as a safe alternative for clopidogrel-associated arthritis. J Invasive Cardiol 2011; 23:E137.
- Khan EA, Blake JW, Stamp LK. Ticlopidine as a safe alternative for clopidogrel-associated arthritis. J Rheumatol 2009; 36:855.
- Dakik HA, Salti I, Haidar R, Uthman IW. Drug points: Ticlopidine associated with acute arthritis. BMJ 2002; 324:27.
- Prescribing information is available through the US Food and Drug Administration website. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.DrugDetails (Accessed on December 04, 2014).
- Vigo PG, MacDowell AL, Wedner HJ. Successful desensitization with clopdogrel after a positive skin test (Abstract 44). Ann Allergy Asthma Immunol 2005; 94:132.
- Guéant-Rodriguez RM, Romano A, Barbaud A, et al. Hypersensitivity reactions to iodinated contrast media. Curr Pharm Des 2006; 12:3359.
- Hasdenteufel F, Waton J, Cordebar V, et al. Delayed hypersensitivity reactions caused by iodixanol: an assessment of cross-reactivity in 22 patients. J Allergy Clin Immunol 2011; 128:1356.
- Jeremias A, Sylvia B, Bridges J, et al. Stent thrombosis after successful sirolimus-eluting stent implantation. Circulation 2004; 109:1930.
- Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005; 293:2126.
- Solensky R. Drug desensitization. Immunol Allergy Clin North Am 2004; 24:425.
- Walker NE, Fasano MB, Hobbs RA, Horwitz PA. Clopidogrel desensitization protocol for the treatment of thienopyridine hypersensitivity. Crit Pathw Cardiol 2007; 6:26.
- Lee-Wong M, Gadhvi D, Resnick D. Clopidogrel desensitization. Ann Allergy Asthma Immunol 2006; 96:756.
- Camara MG, Almeda FQ. Clopidogrel (Plavix) desensitization: a case series. Catheter Cardiovasc Interv 2005; 65:525.
- Fajt M, Petrov A. Clopidogrel hypersensitivity: a novel multi-day outpatient oral desensitization regimen. Ann Pharmacother 2010; 44:11.
- Sanchez-Lopez J, Muñoz-Cano R, Bartra J, et al. Desensitization to clopidogrel: a growing need. Allergy 2010; 65:279.
- Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357:2001.
- Raccah BH, Shalit M, Danenberg HD. Allergic reaction to prasugrel and cross-reactivity with clopidogrel. Int J Cardiol 2012; 157:e48.
- Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015; 372:1791.
- Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361:1045.
- Lokhandwala JO, Best PJ, 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 Interv 2009; 2:348.
- van Werkum JW, Braber TL, Verheggen PW, Van Der Have-Roeffel SM. Prasugrel as alternative treatment strategy in a case with a hypersensitivity reaction to clopidogrel. Platelets 2011; 22:77.
- Peppard SR, Held-Godgluck BM, Beddingfield R. Use of prasugrel in a patient with clopidogrel hypersensitivity. Ann Pharmacother 2011; 45:e54.
- Felix-Getzik E, Sylvia LM. Prasugrel use in a patient allergic to clopidogrel: effect of a drug shortage on selection of dual antiplatelet therapy. Am J Health Syst Pharm 2013; 70:511.
- Siu H, Kaliyadan A, Fischman DL, et al. Use of prasugrel in the setting of clopidogrel hypersensitivity: Case report and systematic review of the literature. Platelets 2016; 27:824.
- Chin N, Rangamuwa K, Mariasoosai R, et al. Oral antiplatelet agent hypersensitivity and cross-reactivity managed by successful desensitisation. Asia Pac Allergy 2015; 5:51.
- Manchette AM, Drucker AG, Januzzi JL Jr. Acute coronary syndrome antiplatelet alternatives in clopidogrel allergy. Pharmacotherapy 2014; 34:e152.
- Harris JR, Coons JC. Ticagrelor Use in a Patient With a Documented Clopidogrel Hypersensitivity. Ann Pharmacother 2014; 48:1230.
- CLINICAL MANIFESTATIONS
- Most common signs and symptoms
- Other cutaneous reactions
- More serious types of systemic reactions
- Allergy testing
- Differential diagnosis
- Reactions that necessitate stopping clopidogrel
- "Treating through"
- - Advantages
- - Advantages
- - Types of clopidogrel reactions that have been managed with desensitization
- - Protocol
- - Success rate
- ALTERNATE THERAPIES
- Other P2Y12 inhibitors
- Cross-reactivity among drugs
- COMMON CLINICAL SCENARIOS
- Reactions soon after initiation
- Retreatment after a past reaction
- SUMMARY AND RECOMMENDATIONS