Publications

Published: December 1998

Azathioprine-Allopurinol Interaction: Danger!

Prescriber Update 17: 16–17
December 1998

Medsafe Editorial Team

Allopurinol and azathioprine should not be co-prescribed unless the combination cannot be avoided. Allopurinol interferes with the metabolism of azathioprine, increasing plasma levels of 6-mercaptopurine which may result in potentially fatal blood dyscrasias. Concomitant use requires special precautions: the dose of azathioprine should be reduced to 25% of the recommended dose and the patient’s blood count should be monitored assiduously.

Bone marrow suppression occurs with azathioprine-allopurinol interaction

The March 1998 meeting of the Medicines Adverse Reactions Committee reviewed a report of an interaction between azathioprine and allopurinol. The patient, who had been taking azathioprine for many years, presented with pancytopenia 2 months after commencing therapy with allopurinol. Recovery followed withdrawal of both medications and transfusion of 2 units of red blood cells. It took the patient about 6 months to feel well again.

Azathioprine is an immunosuppressive agent. It is first metabolised to 6-mercaptopurine, which in turn is converted to inactive products by xanthine oxidase. Allopurinol inhibits the second step of metabolism, and higher 6-mercaptopurine plasma levels result, with associated toxic effects on the bone marrow and other tissues. The resulting blood dyscrasias, leucopenia, thrombocytopenia or pancytopenia, can be life threatening.

If co-prescription unavoidable: reduce azathioprine dose, monitor blood count

Concomitant use of azathioprine and allopurinol should be avoided if possible. However, if co-administration is necessary, the dose of azathioprine should be reduced to 25% of the recommended dose and the patient’s blood count should be checked weekly for the first 3 months of treatment and monthly thereafter to ensure that the dosage can be sustained and is not leading to bone marrow suppression.

The same risk of interaction applies to co-administration of 6-mercaptopurine and allopurinol. When co-administration is necessary, the dose of 6-mercaptopurine should be reduced and blood count monitored.

Warn patients and their GP of potential interaction

When azathioprine is initiated, the prescriber should check that the patient is not taking allopurinol. The patient should be warned that azathioprine interacts with allopurinol, a treatment for gout. The risk associated with an interaction with allopurinol should be conveyed to the patient’s general practitioner.