A 52-year-old man with chronic gout is on azathioprine for autoimmune hepatitis. He is started on allopurinol for recurrent gouty attacks. What is the major risk of this combination?

• A Bone marrow suppression due to azathioprine toxicity ✓
• B Acute gout flare
• C Severe hepatotoxicity
• D Renal failure

Explanation

Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolising azathioprine to inactive metabolites. When allopurinol is co-administered, azathioprine levels rise markedly, leading to severe bone marrow suppression, including leukopenia and thrombocytopenia. The azathioprine dose should be reduced to 25-33% of the usual dose when combined with allopurinol, or an alternative urate-lowering agent should be chosen. Hepatotoxicity and renal failure are not the primary concern with this interaction.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

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