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Methotrexate Drug Interaction — SCE Rheumatology MCQ

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HardRheumatology PharmacologyMethotrexate Drug InteractionSCE Rheumatology

A 50-year-old woman with RA on Methotrexate develops oral mucositis sore throat and a temperature of 38.5°C. Her FBC shows pancytopenia (Hb 82 g/L WCC 0.9 x10^9/L platelets 42 x10^9/L). She reports she has been prescribed Co-trimoxazole by her GP for a urinary tract infection 5 days ago. What is the most likely cause of the pancytopenia?

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Correct answer: C — Methotrexate toxicity potentiated by Co-trimoxazole (Trimethoprim)

Co-trimoxazole contains Trimethoprim, a dihydrofolate reductase inhibitor. When combined with Methotrexate (also a folate antagonist), there is synergistic anti-folate toxicity causing severe myelosuppression. BSR 2025 csDMARD guidelines and the BNF specifically warn against this combination. This interaction is one of the most important drug interactions in rheumatology practice. Emergency management includes stopping both drugs, IV Folinic acid (Calcium folinate), broad-spectrum antibiotics for neutropenic sepsis, and supportive care.

Reference: BSR 2025 csDMARD guidelines; BNF Methotrexate interactions