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Azathioprine – Macrocytosis as Dosing Marker — SCE Neurology MCQ

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ModeratePeripheral Neuropathy & NeuromuscularAzathioprine – Macrocytosis as Dosing MarkerSCE Neurology

A 54-year-old with generalised myasthenia gravis is stable on azathioprine 2 mg/kg daily. A general practitioner starts allopurinol for recurrent gout without changing the azathioprine dose. Two weeks later, she develops fever, mouth ulcers and neutrophils of 0.4 × 10⁹/L. Which is the most likely explanation?

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Correct answer: B — Allopurinol has increased active thiopurine exposure, causing severe myelotoxicity

Xanthine-oxidase inhibition by allopurinol markedly increases exposure to thiopurine metabolites. Co-prescribing with azathioprine can cause dangerous marrow suppression unless the interaction is actively managed with specialist advice and major dose adjustment. Fever, mucosal ulceration and profound neutropenia require urgent assessment and cessation of the implicated drugs rather than attribution to benign macrocytosis.

Reference: Azathioprine Summary of Product Characteristics: https://www.medicines.org.uk/emc/product/14296/smpc