febuxostat and azathioprine

Febuxostat inhibits xanthine oxidase, the enzyme responsible for the metabolism of azathioprine and its active metabolite 6-mercaptopurine. Reduced metabolic clearance leads to accumulation of 6-mercaptopurine and its active metabolites, increasing the risk of severe myelosuppression.

Co-administration can cause life-threatening bone marrow suppression, including neutropenia, thrombocytopenia, and anaemia. This may present as increased susceptibility to infections, bleeding, and fatigue. Fatal outcomes have been reported with similar xanthine oxidase inhibitors.

The combination is contraindicated. Do not prescribe febuxostat with azathioprine. If no alternative urate-lowering therapy is suitable, consider referral to a specialist for management. If combination is deemed absolutely necessary despite the contraindication, extreme caution is required, with substantial dose reduction of azathioprine and frequent monitoring of full blood counts; however, this is rarely acceptable clinical practice.

The interaction is well established for allopurinol and azathioprine, with febuxostat sharing the same mechanism. Product labels for febuxostat contraindicate concurrent use with azathioprine. Direct clinical data for febuxostat are limited, but the class effect is recognised.