Which drug is a selective competitive inhibitor of xanthine oxidase used for chronic gout, and what is the major toxicity that has limited its use in some patients?
- A Allopurinol — Stevens-Johnson syndrome (SJS) is a rare severe cutaneous reaction, particularly in HLA-B*5801 carriers (Han Chinese, Korean, Thai) ✓
- B Febuxostat — less renal toxicity than allopurinol; major concern is cardiovascular mortality in patients with established CVD
- C Probenecid — urate nephropathy and renal stone formation
- D Lesinurad — severe hepatotoxicity limiting use to second line
Correct answer: A. Allopurinol — Stevens-Johnson syndrome (SJS) is a rare severe cutaneous reaction, particularly in HLA-B*5801 carriers (Han Chinese, Korean, Thai)
Explanation
Allopurinol inhibits xanthine oxidase, reducing uric acid production. It is the most widely used urate-lowering drug. Its rare but potentially fatal adverse effect is Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN), which is strongly associated with the HLA-B*5801 allele present at high frequency in Han Chinese, Korean, and Thai populations. CPIC guidelines recommend HLA-B*5801 genotyping before initiating allopurinol in these populations. Febuxostat also inhibits xanthine oxidase but carries a boxed warning for cardiovascular risk.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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