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Gout requiring allopurinol in a patient receiving azathioprine — SCE Rheumatology MCQ

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ModerateAllopurinolGout requiring allopurinol in a patient receiving azathioprineSCE Rheumatology

A 58-year-old woman with systemic lupus erythematosus and previous class IV lupus nephritis takes azathioprine 150 mg daily. Her nephritis is in remission, but previous attempts to reduce immunosuppression precipitated renal relapse. She has had four crystal-proven gout flares in the past year, and her serum urate is 518 micromol/L. Her eGFR is 68 mL/min/1.73 m², full blood count and liver biochemistry are normal, and pretreatment TPMT activity was normal. Following multidisciplinary review, allopurinol is selected for urate-lowering therapy. Substitution or withdrawal of azathioprine is judged to pose an unacceptable risk of lupus relapse, so co-administration is considered clinically necessary. Which is the most appropriate prescribing plan?

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Correct answer: D — Reduce azathioprine to 37.5 mg daily, start allopurinol and arrange frequent blood-count monitoring

Explanation lettering: E = shown as B · B = shown as C · C = shown as E

Allopurinol inhibits xanthine oxidase, which normally contributes to the inactivation of azathioprine-derived 6-mercaptopurine. Co-administration can therefore produce toxic thiopurine exposure, life-threatening myelosuppression and pancytopenia. The combination should generally be avoided; when it is clinically necessary, the azathioprine dose must be reduced to one quarter of its original dose and frequent haematological monitoring instituted. One quarter of 150 mg is 37.5 mg daily. Normal TPMT activity, renal function and baseline blood counts do not remove this pharmacokinetic interaction. Continuing 150 mg (A) is unsafe, while reducing to 75 mg (C) is insufficient. Stopping azathioprine (B) would avoid the interaction but contradicts the stipulated need for continued thiopurine therapy because of her previous renal relapses. Febuxostat (E) is not a safe workaround: it is also a xanthine oxidase inhibitor, and its concomitant administration with azathioprine is not recommended because an adequate azathioprine dose reduction has not been established. Monitoring is an adjunct to, rather than a substitute for, the required dose reduction.

Reference: Zyloric Tablets 100 mg, 300 mg — Summary of Product Characteristics (19 February 2025) — https://www.medicines.org.uk/emc/medicine/4565/SPC/Zyloric%2BTablets%2B100mg%2C%2B300mg Azathioprine 25 mg Film-Coated Tablets — Summary of Product Characteristics (30 October 2025) — https://www.medicines.org.uk/emc/product/11142/smpc