Does Methotrexate Interact with Sulfamethoxazole And Trimethoprim?
Methotrexate and Sulfamethoxazole And Trimethoprim have a contraindicated drug interaction according to U.S. FDA drug labeling data. Sulfonamides displace methotrexate from plasma protein binding and compete with renal transport, increasing free methotrexate concentrations. The mechanism involves protein binding displacement and renal transport competition. Patients taking both medications should consult their healthcare provider before starting, stopping, or changing the dosage of either drug. This information is based on official FDA drug labeling sourced from OpenFDA and the NIH National Library of Medicine.
- Severity
- Contraindicated
- Methotrexate Class
- Folate Analog Metabolic Inhibitor
- Sulfamethoxazole And Trimethoprim Class
- Sulfonamide Antimicrobial
- Management
- Do not take together
- Data Source
- U.S. FDA via OpenFDA
How This Interaction Works
The interaction between Methotrexate and Sulfamethoxazole And Trimethoprim occurs because protein binding displacement and renal transport competition. Clinically, this means sulfonamides displace methotrexate from plasma protein binding and compete with renal transport, increasing free methotrexate concentrations. Because of the severity of this interaction, these medications are contraindicated — meaning they should not be taken together under any circumstances. If you are currently taking both, contact your healthcare provider immediately to discuss alternatives.
What To Tell Your Doctor or Pharmacist
If you are taking Methotrexate and your doctor is considering prescribing Sulfamethoxazole And Trimethoprim (or vice versa), make sure to:
- Inform your doctor and pharmacist of all current medications, including over-the-counter drugs and supplements
- Ask whether the benefits of combining these medications outweigh the risks for your specific situation
- Ask what symptoms to watch for that would indicate the interaction is causing problems
- Ask about alternative medications that do not interact with your current regimen
- Ask how frequently you should be monitored while these are co-prescribed
- Never stop or change either medication without first consulting your healthcare provider