Diflunisal and Methotrexate Interaction
Drug interaction information between Diflunisal and Methotrexate.
Diflunisal and Methotrexate have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Diflunisal and Methotrexate. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.
How They Interact
Diflunisal can prevent your kidneys from clearing methotrexate out of your system, which can lead to toxic levels of the drug in your blood. This makes the side effects of methotrexate much more dangerous.
FDA Label Information
Methotrexate NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.
Diflunisal Also Interacts With
- Cyclosporine moderate
- Celecoxib moderate
- Indomethacin moderate
- Mefenamic Acid moderate
- Meloxicam moderate
Methotrexate Also Interacts With
- Celecoxib moderate
- Indomethacin moderate
- Mefenamic Acid moderate
- Meloxicam moderate
- Misoprostol moderate
Frequently Asked Questions
What SPL severity band is on file for Diflunisal + Methotrexate?
Compiled FDA labeling labels this pair moderate. That is a source-record field, not an individual medication-combination decision.
Which drug in this pair has the larger labeled-interaction portfolio?
Methotrexate has 38 labeled pairs on file vs Diflunisal's 17. In the moderate band specifically: Diflunisal has 11 (also Cyclosporine, Celecoxib, Indomethacin, Mefenamic Acid); Methotrexate has 12 (also Celecoxib, Indomethacin, Mefenamic Acid, Meloxicam).
What mechanism field is on file for Diflunisal and Methotrexate?
Diflunisal can prevent your kidneys from clearing methotrexate out of your system, which can lead to toxic levels of the drug in your blood. This makes the side effects of methotrexate much more dangerous.
Methotrexate's labeled portfolio outnumbers Diflunisal
SPL source-record counts only. This page's band is moderate · classes on file: Diflunisal (Nonsteroidal Anti-Inflammatory Drug (NSAID)); Methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)).
0 major · 11 moderate · 6 minor · 17 total
- Other moderate peers for Diflunisal
- Cyclosporine
- Celecoxib
- Indomethacin
- Mefenamic Acid
0 major · 12 moderate · 26 minor · 38 total
- Other moderate peers for Methotrexate
- Celecoxib
- Indomethacin
- Mefenamic Acid
- Meloxicam
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.
Read our methodology - how this data is sourced, computed, and verified.