trimethoprim + methotrexate

Trimethoprim + methotrexate is a combination of two small molecule drugs, each with distinct mechanisms of action. Trimethoprim is an antifolate antibiotic that inhibits bacterial dihydrofolate reductase, thereby blocking the synthesis of tetrahydrofolic acid and ultimately DNA in bacteria. Methotrexate is an antimetabolite and antifolate agent used primarily as a chemotherapeutic and immunosuppressant; it inhibits human dihydrofolate reductase, disrupting folate metabolism required for DNA synthesis in rapidly dividing cells. This combination does not represent a marketed fixed-dose product but refers to the concurrent use of both agents, which can occur in clinical practice (e.g., patients on methotrexate for autoimmune disease who require trimethoprim for infection prophylaxis or treatment). The combination carries significant risk due to additive antifolate effects leading to increased toxicity such as bone marrow suppression (myelosuppression), leukopenia, transaminitis, and potentially fatal outcomes[2][3][6]. Use together should generally be avoided unless no alternatives exist; if used concomitantly, close monitoring of blood counts and liver function is essential[1][2].