A patient presenting in a community pharmacy is prescribed trimethoprim for a UTI and also takes a medication that can interact fatally with trimethoprim. Which medication is this?

• A. Warfarin
• B. Lithium
• C. Heparin
• D. Methotrexate

Answer: (D)

The key idea is that trimethoprim can dangerously interact with methotrexate because both interfere with folate metabolism, leading to severe suppression of rapidly dividing cells like those in the bone marrow. Trimethoprim acts as a folate pathway inhibitor, and methotrexate is a potent folate antagonist used in higher-dose therapy. When given together, their effects on folate-dependent DNA synthesis add up, dramatically increasing the risk of pancytopenia (low red and white cells and platelets), mucositis, nephrotoxicity, and serious infections. Trimethoprim can also reduce the clearance of methotrexate, raising methotrexate levels and toxicity risk. For these reasons, co-prescribing trimethoprim with methotrexate is potentially life-threatening and usually avoided or requires specialist guidance and monitoring. Other listed drugs may interact with trimethoprim in different ways (for example, Warfarin can have INR effects), but the combination with methotrexate carries the most acute toxicity risk in this context.