Bactrim methotrexateDrug Laboratory Test Interactions : Bactrim, specifically the trimethoprim component, can interfere with a serum methotrexate assay as determined by the competitive . . . . . View complete and up to date Bactrim information - part . . . Other medications to avoid include: Antibiotics such as Keflex and penicillinTrimethoprim/sulfamethoxazole (Bactrim, Septra) can enhance the cytotoxic effects of methotrexate because trimethoprim is an antifolate reductase inhibitor. Dear Ne... more