Febuxostat is a non-purine xanthine oxidase inhibitor used in chronic gout. Compared to allopurinol, which pharmacological advantage does febuxostat offer in patients with mild-to-moderate renal impairment?

• A Febuxostat is renally excreted unchanged, allowing safe dose escalation in renal impairment
• B Febuxostat is primarily hepatically metabolised (CYP1A2, 2C8, UGT), does not require dose adjustment for mild-moderate CKD, and does not produce oxypurinol which accumulates in renal failure ✓
• C Febuxostat inhibits both xanthine oxidase and uricase, providing a dual uric acid-lowering mechanism
• D Febuxostat has no drug interactions with azathioprine unlike allopurinol

Explanation

Allopurinol is converted to oxypurinol (its active metabolite), which is renally excreted. In CKD, oxypurinol accumulates, increasing the risk of allopurinol hypersensitivity syndrome (AHS), necessitating dose reduction. Febuxostat is a non-purine selective xanthine oxidase inhibitor metabolised predominantly by hepatic glucuronidation (UGT) and CYP enzymes; it has dual renal/hepatic elimination and does not produce accumulating renally-cleared metabolites — making dose adjustment unnecessary in mild-to-moderate CKD. Both allopurinol and febuxostat dangerously inhibit azathioprine metabolism (xanthine oxidase converts 6-mercaptopurine to inactive products; inhibition causes 6-MP toxicity) — this interaction applies to both.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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