American Board of Internal Medicine (ABIM) Certification Practice Exam

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What should patients taking azathioprine be cautious of, especially when using febuxostat?

Possible liver toxicity
Dangerously high azathioprine levels
Increased risk of infections
Gastrointestinal irritation

The correct answer is: Dangerously high azathioprine levels

Patients taking azathioprine should be particularly cautious about the potentially dangerously high levels of azathioprine when using febuxostat, as febuxostat can significantly affect the metabolism of azathioprine. Azathioprine is metabolized by the enzyme thiopurine methyltransferase (TPMT), and febuxostat can inhibit another enzyme involved in purine metabolism, leading to decreased clearance of azathioprine. When febuxostat is introduced into a treatment regimen that includes azathioprine, it can result in elevated levels of the drug in the body. This elevation raises the risk of toxicity, which can manifest as bone marrow suppression, hepatotoxicity, and increased susceptibility to infections. Therefore, close monitoring of blood levels is essential, especially at the initiation of febuxostat therapy for patients already receiving azathioprine. Understanding this interaction is crucial in managing patients appropriately and adjusting azathioprine dosages if febuxostat is added to the treatment plan.