Sulfamethizole and Methotrexate Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methotrexate Injection
Sulfamethizole
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
An increased risk of methotrexate toxicity (myelotoxicity, pancytopenia, megaloblastic anemia)
Interaction Deep Dive
Sulfamethizole may displace methotrexate from protein binding sites. The therapeutic effect and/or toxic effects of methotrexate may be enhanced by sulfamethizole, therefore dosage adjustment may be necessary1.
Why it happens (mechanism)
Protein binding displacement, decreased renal tubular elimination
Common questions
Can I take Sulfamethizole and Methotrexate Injection together?
An increased risk of methotrexate toxicity (myelotoxicity, pancytopenia, megaloblastic anemia) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Sulfamethizole and Methotrexate Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Sulfamethizole or Methotrexate Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: Methotrexate LPF(R), methotrexate. Xanodyne Pharmacal, Inc. Florence, KY, 2003. DailyMed
Keep reading about Methotrexate Injection
Keep reading about Sulfamethizole
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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