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Methotrexate Drug Interaction — SCE Dermatology MCQ

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EasyDermatopharmacologyMethotrexate Drug InteractionSCE Dermatology

A 35-year-old woman with psoriasis is on Methotrexate. She is admitted with acute community-acquired pneumonia. Her regular medications include Methotrexate 15 mg weekly and Folic acid 5 mg weekly. The admitting team prescribes Co-trimoxazole for pneumonia. What is the critical concern?

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Correct answer: C — Co-trimoxazole is CONTRAINDICATED with Methotrexate due to fatal additive antifolate toxicity (pancytopenia)

Co-trimoxazole (Trimethoprim + Sulfamethoxazole) combined with Methotrexate is potentially FATAL. Trimethoprim inhibits dihydrofolate reductase (same target as Methotrexate) causing synergistic/additive folate antagonism; Sulfamethoxazole inhibits folate synthesis and competes for renal tubular secretion of Methotrexate. The combination causes severe pancytopenia. This interaction is specifically highlighted in NPSA and MHRA patient safety alerts. Multiple deaths have been reported. Patients on Methotrexate should carry an alert card. Prescribers must check for Methotrexate before prescribing Trimethoprim or Co-trimoxazole. Alternative antibiotics (Amoxicillin, Doxycycline, Clarithromycin) should be used.

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