Allopurinol × Azathioprine

Azathioprine is converted to 6-mercaptopurine, and xanthine oxidase turns its active metabolites into inactive 6-thiouric acid. Allopurinol blocks xanthine oxidase, so azathioprine and 6-mercaptopurine accumulate. Levels can reach the toxic range with pancytopenia and bone marrow suppression; the Spanish allopurinol SmPC mentions fatal cases. No official label lists the pair as a contraindication: the allopurinol SmPC and the FDA label require a steep cut in the azathioprine dose.

Bone marrow suppression: falling white cells, platelets and haemoglobin, up to pancytopenia. The patient notices sore throat, fever, unexplained bruising or bleeding – the signs the allopurinol SmPC asks patients to report at once.

Avoid the combination where possible, as the allopurinol SmPC requires. If it is clinically necessary, cut the azathioprine dose to a quarter of the usual dose (allopurinol and azathioprine SmPCs; FDA label: 1/3 to 1/4) and check full blood counts often. The azathioprine SmPC already asks for weekly or more frequent counts with platelets during the first 8 weeks of therapy. Febuxostat is not a substitute: it blocks the same enzyme, the FDA contraindicates it with azathioprine and the EU SmPC does not recommend it.