allopurinol and azathioprine

MajorAvoid this combination where possible.

Mechanism

Allopurinol inhibits xanthine oxidase, the enzyme responsible for the inactivation of the azathioprine metabolite 6-mercaptopurine (its conversion to thiouric acid). This inhibition markedly increases the concentrations of 6-mercaptopurine and its metabolites, ...

What it means clinically

Concurrent use can cause severe, potentially fatal bone marrow suppression, including leucopenia, thrombocytopenia, and anaemia. Patients are at increased risk of serious infections and bleeding. Fatal outcomes have been reported.

What to do

Avoid co-prescription. If unavoidable, reduce the azathioprine dose to approximately one quarter of the usual dose and monitor full blood count closely, especially during the first few weeks of therapy. Consider alternative agents or use of allopurinol with a different immunosuppressant.

Evidence

Well-established interaction, widely documented in drug interaction databases and prescribing information. Clinical pharmacokinetic and pharmacodynamic studies support the mechanism.

The two drugs

allopurinolxanthine oxidase inhibitorRead the monograph azathioprineimmunosuppressantRead the monograph

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Other interactions involving allopurinol or azathioprine

Educational reference for students and clinicians in training. It does not replace professional judgement, local protocols or current prescribing information.