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Rash with Both Clopidogrel and Ticlopidine in Two Patients Following Percutaneous Coronary Intervention with Drug-Eluting Stents

Resident in Pharmacy Practice, Mercy Suburban Hospital, Norristown, PA

Robert L Wilensky, MD

Associate Professor of Medicine, Department of Medicine, Cardiovascular Division, University of Pennsylvania, Philadelphia, PA

Maureen Burke Julien, MSN CRNP

Nurse Practitioner, Interventional Cardiology, Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia

Howard C Herrmann, MD

Professor of Medicine, Department of Medicine, Cardiovascular Division, University of Pennsylvania

Sarah A Spinler, PharmD FCCP

Professor of Clinical Pharmacy, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia; Adjunct Professor of Pharmacy in Medicine, Department of Medicine, Cardiovascular Division, University of Pennsylvania

Reprints: Dr. Spinler, University of the Sciences in Philadelphia, 600 S. 43rd St., Philadelphia, PA 19104-4495, fax 215/596-8586, s.spinle{at}usip.edu

OBJECTIVE: To describe 2 cases of rash that occurred following oral administration of both clopidogrel and ticlopidine and to review previously published case reports.

CASE SUMMARY: Two patients developed maculopapular pruritic rashes that began on the abdomen and spread to the back, neck, and face following clopidogrel administration after placement of a drug-eluting intracoronary stent. Following recurrence of the rash after ticlopidine was initiated, thienopyridines were discontinued, and the patients were treated for 3-6 months with aspirin, cilostazol, and enoxaparin or warfarin for prevention of stent thrombosis and reinfarction. One patient self-discontinued cilostazol, reinitiated clopidogrel, and redeveloped a rash.

DISCUSSION: While there have been several published cases of thienopyridine-associated rash, there have been only 2 reported cases of cross-sensitivity between orally administered clopidogrel and ticlopidine. Preliminary reports suggest that clopidogrel desensitization may be accomplished in selected patients several months to years following thienopyridine rash using an allergy desensitization protocol, with close monitoring for anaphylaxis. An objective causality assessment using the Naranjo probability scale indicated that both ticlopidine and clopidogrel were probable causes of the rash in the first patient; in the second patient, clopidogrel was judged a definite cause and ticlopidine was a probable cause of the rash.

CONCLUSIONS: In a patient who develops a rash following clopidogrel treatment after intracoronary stent placement, ticlopidine therapy should be attempted, provided the initial reaction did not include life-threatening symptoms. In a patient who experiences rash with both clopidogrel and ticlopidine and does not have a contraindication to cilostazol or anticoagulation, therapy with aspirin, cilostazol, and either enoxaparin or warfarin may be administered for 2-6 months following placement of a drug-eluting stent.

Key Words: cilostazol, clopidogrel, desensitization, drug-eluting stent, enoxaparin, ticlopidine

Published Online, May 9, 2006. www.theannals.com, DOI 10.1345/aph.1G587

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