American Board of Internal Medicine (ABIM) Certification Practice Exam

Which purine analogue should febuxostat be avoided with due to potential toxicity?

1. Azathioprine

2. 6-mercaptopurine

3. Both azathioprine and 6-mercaptopurine

4. None of the above

The correct answer is: Both azathioprine and 6-mercaptopurine

Febuxostat is a xanthine oxidase inhibitor primarily used in the treatment of hyperuricemia associated with gout. It lowers uric acid levels by inhibiting the conversion of hypoxanthine and xanthine to uric acid. In patients who are being treated with purine analogues such as azathioprine or 6-mercaptopurine, combining these medications with febuxostat can lead to increased toxicity. Azathioprine and 6-mercaptopurine are prodrugs that require conversion to active metabolites. The metabolism of these drugs involves the enzyme thiopurine methyltransferase (TPMT) as well as xanthine oxidase. When febuxostat inhibits xanthine oxidase, it can lead to decreased clearance of these purine analogues. Consequently, this can result in elevated levels of active metabolites, which increases the risk of toxicity, including bone marrow suppression and increased susceptibility to infections. Therefore, because of the potential for increased toxicity from these purine analogues when taken with febuxostat, it is advisable to avoid using these medications concurrently. This understanding underscores the reason why both azathioprine and 6-mercaptopurine should be avoided in patients receiving