Allopurinol inhibits xanthine oxidase, the enzyme that inactivates 6-mercaptopurine (the active metabolite of azathioprine). Plasma 6-MP rises 5-fold, causing fatal myelosuppression: pancytopenia, agranulocytosis, thrombocytopenia. FDA boxed warning on azathioprine label.
Symptoms
Within 1–4 weeks: fever, infections, bleeding, bruising. CBC shows steep drop in leukocytes and platelets up to agranulocytosis. Without allopurinol withdrawal mortality reaches 30%.
Management
Combination contraindicated. If urate-lowering therapy is required during azathioprine immunosuppression, use febuxostat with caution or reduce azathioprine to 25% of baseline with weekly CBC for the first 2 months.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.