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Methotrexate Drug Interaction — SCE Dermatology MCQ

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EasyDermatopharmacologyMethotrexate Drug InteractionSCE Dermatology

A 48-year-old woman with psoriasis on Methotrexate is prescribed Trimethoprim by her GP for a UTI. Within 5 days she develops oral ulceration, malaise, and a falling white cell count. What is the mechanism of this drug interaction?

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Correct answer: E — Both drugs inhibit folate metabolism causing additive bone marrow suppression

Trimethoprim and Methotrexate both inhibit folate metabolism (Trimethoprim inhibits bacterial dihydrofolate reductase but also weakly inhibits the human enzyme; Methotrexate potently inhibits dihydrofolate reductase). The combination causes synergistic/additive folate antagonism leading to potentially fatal pancytopenia. This is a well-known, life-threatening drug interaction highlighted by NPSA and MHRA safety alerts. Co-trimoxazole (Trimethoprim + Sulfamethoxazole) is even more dangerous. BAD guidelines and the BNF explicitly contraindicate this combination. Patients on Methotrexate should carry a patient-held record card listing interacting drugs.

Reference: BAD 2016 Methotrexate Guidelines; NPSA; MHRA; BNF