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Drug Interaction — SCE Rheumatology MCQ

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ModerateRheumatology PharmacologyDrug InteractionSCE Rheumatology

A 55-year-old man with rheumatoid arthritis takes azathioprine and is also receiving allopurinol for gout. Which mechanism explains the potentially life-threatening interaction between these drugs?

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Correct answer: A — Allopurinol inhibits xanthine oxidase, reducing thiopurine inactivation and causing severe myelosuppression

Azathioprine is converted to 6-mercaptopurine, which is partly inactivated through xanthine oxidase. Allopurinol inhibits this enzyme, reducing thiopurine catabolism and potentially causing profound, life-threatening myelosuppression or pancytopenia. The combination should generally be avoided. If co-administration is clinically necessary, the azathioprine dose should be reduced to 25% of the usual dose and frequent haematological monitoring undertaken. This interaction is not mediated by enhanced TPMT activity or renal retention, and the major clinical consequence is thiopurine toxicity rather than loss of allopurinol efficacy. Therefore, E is the single best answer.

Reference: Electronic Medicines Compendium, Azathioprine tablets 50 mg, Summary of Product Characteristics, sections 4.2 and 4.5, 2026. https://www.medicines.org.uk/emc/product/14296/smpc