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Methotrexate Toxicity — RACP Adult Medicine MCQ

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ModerateClinical PharmacologyMethotrexate ToxicityRACP Adult Medicine

A 78-year-old man on long-term methotrexate for rheumatoid arthritis develops pancytopaenia (WCC 1.5 × 10⁹/L, Hb 82 g/L, platelets 55 × 10⁹/L). His creatinine has risen to 200 µmol/L from a baseline of 110 µmol/L. What is the most important immediate management?

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Correct answer: D — Cease methotrexate and administer IV folinic acid (leucovorin)

Methotrexate toxicity with pancytopaenia is a medical emergency. Renal impairment reduces methotrexate clearance, leading to accumulation. Immediate management is to cease methotrexate and give IV folinic acid (leucovorin – not folic acid) as a 'rescue' agent, which bypasses the dihydrofolate reductase block. Dose: 20 mg IV 6-hourly until counts recover. Folic acid alone is insufficient as it competes with methotrexate for the same enzyme.

Reference: AMH – 2025 – Methotrexate; eTG – 2025 – Rheumatology