Febuxostat inhibits xanthine oxidase non-competitively and is preferred over allopurinol in certain patients with gout. The key pharmacogenomic reason febuxostat is preferred in patients with HLA-B*5801 allele is:

• A HLA-B*5801 allele is associated with severe allopurinol hypersensitivity syndrome (AHS) including SJS/TEN; febuxostat does not share this pharmacogenomic risk ✓
• B Febuxostat has no xanthine oxidase inhibiting activity in HLA-B*5801 carriers, so allopurinol must be used
• C CYP2C9 poor metabolisers (who carry HLA-B*5801) cannot metabolise allopurinol, causing toxic accumulation
• D HLA-B*5801 carriers overexpress xanthine oxidase, making allopurinol's competitive inhibition insufficient

Explanation

HLA-B*5801 is a pharmacogenomic risk allele for allopurinol hypersensitivity syndrome (AHS), a severe T-cell-mediated drug hypersensitivity that can progress to SJS/TEN with mortality up to 20–30%. The prevalence of HLA-B*5801 is high in Han Chinese (~6–8%), Thai (~8%), and Korean (~12%) populations but lower in Europeans (~1–2%). In high-risk populations, HLA-B*5801 screening before allopurinol initiation is recommended (adopted in Taiwan's drug label). Febuxostat is a non-purine xanthine oxidase inhibitor structurally unrelated to allopurinol and does not cross-react with this HLA allele.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.