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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
💊 Methotrexate(Otrexup)+💊 Sulfamethoxazole And Trimethoprim(Bactrim)

Severity & Interaction Details

⛔
contraindicated
Avoid this combination
FDA labeling lists this pair as contraindicated. The risk outweighs the benefit in nearly all cases.
Severity scale
MinorContra
On record
Yes
Drug A class
Folate Analog Metabolic Inhibitor
Drug B class
Sulfonamide Antimicrobial
Source
NLP:sulfamethoxazole and trimethoprim

What this means in plain English

Sulfonamides displace methotrexate from plasma protein binding and compete with renal transport, increasing free methotrexate concentrations.

About Methotrexate and Sulfamethoxazole And Trimethoprim

Methotrexate is a Folate Analog Metabolic Inhibitor, while Sulfamethoxazole And Trimethoprim is a Sulfonamide Antimicrobial. You may recognize them by the brand names Otrexup and Bactrim. Methotrexate is given by intramuscular injection, whereas Sulfamethoxazole And Trimethoprim is taken by mouth. Methotrexate additionally carries an FDA boxed warning, the FDA's strongest safety alert.

What the FDA label says

"Protein binding displacement and renal transport competition"

📖 Source: NLP:sulfamethoxazole and trimethoprim

Recent research & FDA safety updates

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Auto-aggregated from PubMed E-utilities and FDA safety data.

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Data integrity: Every interaction shown is extracted directly from official U.S. FDA drug labeling via openFDA and the U.S. National Library of Medicine (NIH) — no interactions are invented, inferred, or manually edited. Maintained by CheckDrugInteractions.com. See our methodology or report a correction at support@checkdruginteractions.com.

Data sourced from U.S. FDA drug labeling via openFDA and the NIH National Library of Medicine, supplemented with a small number of well-established interactions from curated clinical references. For informational purposes only. Always consult your pharmacist or physician.