Azathioprine × Febuxostat

Febuxostat inhibits xanthine oxidase, the enzyme that converts 6-mercaptopurine, the active metabolite of azathioprine, into an inactive form. In an interaction study febuxostat reduced 6-mercaptopurine clearance by about 83% after a single dose of azathioprine. The FDA lists the combination as a contraindication in section 4 of the febuxostat label. The EU SmPC does not recommend it and, if it cannot be avoided, requires cutting the azathioprine dose to 20% or less of the previous dose.

Same as with allopurinol: pancytopenia with fever, infections and bleeding within the first weeks of therapy.

Combination contraindicated. To treat hyperuricaemia in patients on azathioprine, use other classes: probenecid if renal function is preserved or pegloticase for severe gout.