Test your medicine knowledge with the MKSAP challenge, in partnership with the American College of Physicians.
A 55-year-old man is evaluated during a follow-up visit for gout. Two years ago, he had been treated with allopurinol and developed a hypersensitivity reaction. Over the past several months, he has had recurrent attacks of acute, episodic swelling of the first metatarsophalangeal joints with increasing involvement of other joints, including the ankles and knees. Laboratory studies showed significant hyperuricemia. History is also significant for Crohn disease, hypertension, chronic kidney disease (estimated glomerular filtration rate of 55 mL/min/1.73 m2), and nonalcoholic fatty liver disease. Current medications are diltiazem and azathioprine, which he has been taking for the past 9 months.
On physical examination, temperature is 37.1 °C (98.8 °F), blood pressure is 125/70 mm Hg, pulse rate is 80/min, and respiration rate is 12/min. BMI is 28. The examination is unremarkable, including no joint abnormalities.
Which of the following is a contraindication to the use of febuxostat in this patient?
A. Azathioprine
B. Diltiazem
C. Mild to moderate chronic kidney disease
D. Nonalcoholic fatty liver disease
MKSAP Answer and Critique
The correct answer is A. Azathioprine.
Azathioprine is a contraindication to the use of febuxostat in this patient with gout. Febuxostat is a non-purine, non-competitive xanthine oxidase inhibitor that blocks urate synthesis by inhibiting xanthine oxidase, the final enzyme in the pathway of urate synthesis from purine precursors. It can be utilized when a patient has intolerance to or failure of allopurinol. Azathioprine, a purine analogue used in the treatment of inflammatory bowel disease, undergoes metabolism via xanthine oxidase. Thus, concomitant use of febuxostat (a xanthine oxidase inhibitor) can lead to dangerously high levels of azathioprine. Of note, use of allopurinol (also an xanthine oxidase inhibitor) concomitantly with azathioprine also poses a risk and is relatively contraindicated; however, some practitioners have used allopurinol in this setting with dose reduction and careful monitoring.
Use of diltiazem is a relative contraindication to colchicine, not febuxostat. Diltiazem is a moderate CYP34A inhibitor, and coadministration of this agent with colchicine can cause elevated colchicine levels.
Moderate chronic kidney disease (estimated glomerular filtration rate, 30-59 mL/min/1.73 m2) is not a contraindication to the use of febuxostat; no dose adjustment to this medication is needed in the setting of mild to moderate kidney impairment.
Nonalcoholic fatty liver disease is not a contraindication to febuxostat use, although monitoring of hepatic function with administration of the drug is indicated.
Key Point
- The xanthine oxidase inhibitor febuxostat is contraindicated in patients taking azathioprine, which undergoes metabolism via xanthine oxidase; concomitant use of these agents can lead to dangerously high levels of azathioprine.
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