Mefenamic Acid and Methotrexate Interaction
Drug interaction information between Mefenamic Acid and Methotrexate.
Mefenamic Acid and Methotrexate have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Mefenamic Acid 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
This pain medicine can prevent your body from clearing out methotrexate, which can lead to toxic levels in your system.
FDA Label Information
Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction). Intervention: During concomitant use of mefenamic acid and methotrexate, monitor patients for methotrexate toxicity.
Mefenamic Acid Also Interacts With
- Diflunisal moderate
- Warfarin moderate
- Meloxicam minor
- Furosemide minor
- Aspirin minor
Methotrexate Also Interacts With
- Celecoxib moderate
- Diflunisal moderate
- Indomethacin moderate
- Meloxicam moderate
- Misoprostol moderate
Frequently Asked Questions
What SPL severity band is on file for Mefenamic Acid + 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 Mefenamic Acid's 15. In the moderate band specifically: Mefenamic Acid has 3 (also Diflunisal, Warfarin); Methotrexate has 12 (also Celecoxib, Diflunisal, Indomethacin, Meloxicam).
What mechanism field is on file for Mefenamic Acid and Methotrexate?
This pain medicine can prevent your body from clearing out methotrexate, which can lead to toxic levels in your system.
Methotrexate's labeled portfolio outnumbers Mefenamic Acid
SPL source-record counts only. This page's band is moderate · classes on file: Mefenamic Acid (Nonsteroidal Anti-Inflammatory Drug (NSAID)); Methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)).
0 major · 3 moderate · 12 minor · 15 total
- Other moderate peers for Mefenamic Acid
- Diflunisal
- Warfarin
0 major · 12 moderate · 26 minor · 38 total
- Other moderate peers for Methotrexate
- Celecoxib
- Diflunisal
- Indomethacin
- 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.