Methotrexate has some immunosuppressive activity and therefore the immunological response to concurrent vaccination may be decreased. In addition, concomitant use of a live vaccine could cause a severe antigenic reaction.
Protein bound methotrexate may be displaced by salicylates, sulphonamides, diphenylhydantoins, tetracyclines, chloramphenicol, sulfazole, doxorubicin, cyclophosphamide and barbiturates. The higher plasma levels of unbound methotrexate may lead to increased toxicity.
Methotrexate is subject to active renal secretion. It interferes in general with other drugs subject to the same excretion-mode and this causes increased Methotrexate plasma-levels.
The dose of methotrexate should be reduced when given concomitantly with probenecid.
Vinca alkaloids may increase intracellular methotrexate and methotrexate polyglutamates.
Concomitant use of drugs with nephrotoxic or hepatotoxic potential (including alcohol) should be avoided.
Vitamin preparations or oral iron preparations containing folic acid may alter the response to methotrexate.
Non-steroidal anti-inflammatory drugs may impair the renal clearance of methotrexate and lead to severe toxicity.
Serum levels of methotrexate may be increased by etretinate and severe hepatitis has been reported following concurrent use.
Concomitant administration of folate antagonists such as trimethoprim/sulphamethoxazole is reported to cause acute pancytopenia in rare cases.