Methotrexate and Silver Sulfadiazine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methotrexate
Silver Sulfadiazine
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
Increased methotrexate exposure, decreased metabolite formation and increased risk of adverse events and decreased efficacy
Interaction Deep Dive
Concomitant use of methotrexate with antifolate agents, including sulfonamides, may increase methotrexate plasma concentrations, which may increase the risk of methotrexate severe adverse reactions. Coadministration of methotrexate with these products may also subsequently reduce active metabolite formation, which may decrease the clinical effectiveness of methotrexate. If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions1.
Why it happens (mechanism)
Unspecified mechanism
Common questions
Can I take Methotrexate and Silver Sulfadiazine together?
Increased methotrexate exposure, decreased metabolite formation and increased risk of adverse events and decreased efficacy Always confirm with your pharmacist or prescriber before making any change.
How serious is the Methotrexate and Silver Sulfadiazine 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Methotrexate or Silver Sulfadiazine 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 SODIUM oral tablets, methotrexate sodium oral tablets. Hikma Pharmaceuticals USA Inc (per Dailymed), Berkeley Heights, NJ, 2024. DailyMed
Keep reading about Methotrexate
Keep reading about Silver Sulfadiazine
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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