Co-trimoxazole × Methotrexate

Co-trimoxazole contains trimethoprim, a dihydrofolate reductase inhibitor. Methotrexate blocks the same enzyme system. Co-administration intensifies the antifolate effect and suppresses haematopoiesis. Fatal pancytopenia and severe mucositis have been reported, even at low rheumatological methotrexate doses.

Stomatitis, mouth ulcers, nausea. Then – falling leukocyte and platelet counts: increased infection susceptibility and bleeding. Severe cases progress to fatal pancytopenia. Symptoms appear after 1–2 weeks of combined dosing.

The combination is not recommended. For urinary tract infections in a patient on methotrexate, use nitrofurantoin or fosfomycin. For Pneumocystis infection where co-trimoxazole cannot be replaced, hold methotrexate for the antibiotic course and check full blood count every 3–5 days. Folic acid supplementation is mandatory.