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Thread: Pharmacogenetics of Allopurinol and Its Fatal Hepatotoxicity

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    PharmD Year 1 TomHsiung's Avatar
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    Default Pharmacogenetics of Allopurinol and Its Fatal Hepatotoxicity

    The ACR TFP considered the issue of measures to reduce the incidence of severe allopurinol hypersensitivity reactions, termed allopurinol hypersensitivity syndrome (AHS).

    The rate of ohspitalization and severe morbidity & mortality due to AHS is 20-25%. The estimated incidence of AHS is ~1:1000 in the US, and its spectrum includes not only Stevens-Johnson syndrome and toxic epidermal necrolysis, but also systemic disease with a clinical constellation of features such as eosinophilia, vasculitis, rash, and major end-organ disease.

    Concurrent thiazide use and renal impairment have been implicated as risk factors for AHS.

    The pharmacogentics of allopurinol referable to AHS is the HLA-B*5801. THe screen of HLA-B*5801 should be considered in select patient subpopulations at an elevated risk for AHS. The reason for this is that those with HLA-B*5801 and of Korean descent with stage 3 or worse CKD (HLA-B*5801 allele frequency ~12%), or of Han Chinese or Thai extraction irrespective of renal function (HLA-B*5801 allele frequency ~6-8%), have been highlighted in the literature as prime examples of subjects at high risk for AHS, marked by HLA-B*5801 hazard ratios of several hundred.

    Such high-risk individuals were recommended to be prescribed an alternative to allopurinol if HLA-B*5801 positive.

    However, in China, there is no such a test to screen for HLA-B*5801.
    Last edited by TomHsiung; Wed 19th March '14 at 9:56pm.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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    PharmD Year 1 TomHsiung's Avatar
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    References:

    1.Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population. Strong association between HLA-B*5801... [Pharmacogenet Genomics. 2009] - PubMed - NCBI

    2.Allopurinol Therapy and HLA-B*5801 Genotype. Allopurinol Therapy and HLA-B*5801 Genotype - Medical Genetics Summaries - NCBI Bookshelf

    3.Association of HLA-B*5801 allele and allopurinol-induced Stevens Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. Association of HLA-B*5801 allele and allopurinol-induced Stevens Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis - National Library of Medicine - PubMed Health
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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