Clopidogrel (Plavix) desensitization: A case series

Abstract

Clopidogrel (Plavix) is a thiopyridine that inhibits the ADP-dependent pathway for platelet activation and has been shown in numerous trials to be effective for a wide variety of patients with cardiovascular disease, particularly those who have undergone coronary stent implantation and who present with acute coronary syndromes. Allergic rashes are one of the common side effects of clopidogrel, which leads to its discontinuation. Type I (Gell and Combs classification) allergic reactions to drugs may be amenable to drug desensitization, allowing safe and prolonged use of the drug. This case series describes a protocol for clopidogrel desensitization over an 8-hr period using 15 doubling doses of clopidogrel given by mouth to achieve a maintenance dose of 75 mg a day. This case series suggests that patients who have had type I drug allergy to clopidogrel may be rapidly desensitized using this protocol. Further studies enrolling a larger number of patients are indicated to confirm the safety and efficacy of this regimen.

Clopidogrel hypersensitivity: clinical challenges and options for management

“…They report on successful inpatient and outpatient desensitization in 3 patients presenting with clopidogrel hypersensitity rash [40]. Two of the three patients in this case-series had experienced hypersensitivity with both clopidogrel and ticlopidine, necessitating desensitization.…”

“…Cross-reactivity between clopidogrel and ticlopidine has been described in several case reports [27,39,40,41] patients to receive either ticlopidine 250 mg twice daily or warfarin adjusted to an INR of 2.5-3.0 for 6 weeks after PCI. Warfarin therapy resulted in a 50% increase in bleeding complications without affecting the rate of MI, death, or stent occlusion.…”

“…A second theory proposes a state of mast cell unresponsiveness develops from gradual antigen exposure. By supplying antigen in small incremental doses, the IgE receptors are slowly bound and occupied without triggering mast cell activation [40]. Likely, both of these pathways contribute to the success of desensitization.…”

“…Patients were desensitized by von Tiehl et al using an 8-hour protocol modified from Camara and Almeda [40]. In contrast to other case reports, patients were bridged through the washout period using ticlopidine, a thienopyridine similar in structure to clopidogrel.…”

Frequency of Allergic or Hematologic Adverse Reactions to Ticlopidine Among Patients With Allergic or Hematologic Adverse Reactions to Clopidogrel

“…11,12 The current study is the first to identify a relatively large number of patients with an allergic or hematologic adverse reaction to one thienopyridine who received the other thienopyridine, and to suggest that the frequency of cross-reactivity between the 2 agents is clinically significant.…”