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Predicting possible zonisamide hypersensitivity syndrome

Authors

  • Manuela G. Neuman,

    1. In Vitro Drug Safety and Biotechnology Laboratory, MaRS Discovery Centre, University of Toronto, Toronto, ON, Canada
    2. Department of Pharmacology and Institute of Drug Research, University of Toronto, Toronto, ON, Canada
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  • Neil H. Shear,

    1. Department of Pharmacology and Institute of Drug Research, University of Toronto, Toronto, ON, Canada
    2. Drug Safety Clinic, Division of Dermatology, University of Toronto, Toronto, ON, Canada
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  • Izabella M. Malkiewicz,

    1. In Vitro Drug Safety and Biotechnology Laboratory, MaRS Discovery Centre, University of Toronto, Toronto, ON, Canada
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  • Mona Kessas,

    1. In Vitro Drug Safety and Biotechnology Laboratory, MaRS Discovery Centre, University of Toronto, Toronto, ON, Canada
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  • Amy W. Lee,

    1. In Vitro Drug Safety and Biotechnology Laboratory, MaRS Discovery Centre, University of Toronto, Toronto, ON, Canada
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  • Lawrence Cohen

    1. Division of Gastroenterology, Sunnybrook Sciences Centre, University of Toronto, Toronto, ON, Canada
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Manuela Neuman, PhD, In Vitro Drug Safety and BioTechnology, MaRS Discovery District, 101 College Street, Suite 200, Lab 351, Toronto, ON M5G 1L7, Canada, Tel.: +1 416 673 6685; Office: +1 416 398 4880, e-mail: manuela.neuman@utoronto.ca; http://www.marsdd.com/tenantdirectory/invitro.html

Abstract

Abstract:  Zonisamide (ZNS) is an anticonvulsant (AC) that contains a sulpha moiety potentially triggering hypersensitivity syndrome reactions (HSR). The lymphocyte toxicity assay (LTA) is an in vitro drug rechallenge test, which is believed to reflect a decreased capacity of the individual to detoxify reactive metabolites. The study examined whether cross-reactivity is present between ZNS and other AC and/or sulphonamides and if this HSR may be predicted using the LTA. The second aim was to determine age-related differences in ZNS-induced HSR. LTA was previously validated in patients who received sulphamethoxazole (SMX) or AC.

Methods:  Forty adult patients who displayed clinical HSR to SMX (20) or AC (20) participated in the study. Each group was represented with an equal number of individuals above and below the age of 60. LTA-SMX, LTA-AC and LTA-ZNS from 20 patients who previously presented a clinical reaction to one of the drugs and who had a positive LTA result to the specific drug were compared with 20 individuals who received the same drugs but did not present reactions. Binary logistic regression was used to evaluate the statistical significance.

Results: In vitro results correlated with the clinical diagnosis. LTA presented a significant difference (P < 0.0001) between control and hypersensitive patients. In each age group, only a single patient had a severe clinical manifestation of SMX-HSR. These individuals tested positive to both SMX and ZNS.

Conclusions:  Sulphamethoxazole-HSR but not AC-HSR patients may present a cross-reactivity to ZNS-HSR. The use of LTA to predict a possible ZNS reaction is recommended for SMX-sensitive individuals who prescribed ZNS.

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