Drug interactions with methotrexate.

General mechanisms of drug interactions are reviewed, as well as the effects of various drugs on the absorption, distribution, protein binding, eliminations and cellular transport of methotrexate. Published studies demonstrate that prior or concomitant administration of other drugs can alter the efficacy and toxicity of methotrexate. Nonabsorbable antibiotics can decrease methotrexate absorption. Nephrotoxic drugs can decrease methotrexate renal clearance. Salicylates and probenecid may decrease the plasma protein binding and renal tubular secretion of methotrexate. However, the clinical significance of many of these drug interactions is not known or has not been substantiated by extensive clinical observations.