A 58-year-old man with a history of kidney transplant presents with severe foot pain and swelling in the first metatarsophalangeal joint. He is on tacrolimus and mycophenolate. Synovial fluid shows negatively birefringent needle-shaped crystals. Serum uric acid is 10.2 mg/dL. Which urate-lowering therapy is most appropriate given his immunosuppressive regimen?
- A Allopurinol at full dose (300 mg/day) without dose adjustment
- B Probenecid, as it is the safest uricosuric in transplant recipients
- C Febuxostat, as it lacks the dangerous interaction with azathioprine seen with allopurinol, and is safer with tacrolimus ✓
- D Rasburicase for acute management followed by pegloticase for maintenance
Explanation
In transplant recipients on azathioprine, allopurinol is hazardous because it inhibits xanthine oxidase (the enzyme that inactivates azathioprine's toxic metabolite 6-thiouanine), causing potentially fatal azathioprine toxicity. This patient is on mycophenolate (not azathioprine), so allopurinol could be used, but febuxostat still offers a safer option with less interaction concern. However, the key principle tested is that febuxostat (a non-purine xanthine oxidase inhibitor) is preferred when azathioprine is co-prescribed. Probenecid is unreliable in CKD. Rasburicase/pegloticase are reserved for refractory or tophaceous gout.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.