Methotrexate and Mefenamic Acid Interaction
Drug interaction information between Methotrexate and Mefenamic Acid.
Methotrexate and Mefenamic Acid have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Methotrexate and Mefenamic Acid. 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.
Methotrexate Also Interacts With
- Celecoxib moderate
- Diflunisal moderate
- Indomethacin moderate
- Meloxicam moderate
- Misoprostol moderate
Mefenamic Acid Also Interacts With
- Diflunisal moderate
- Warfarin moderate
- Meloxicam minor
- Furosemide minor
- Aspirin minor
Frequently Asked Questions
What SPL severity band is on file for Methotrexate + Mefenamic Acid?
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: Methotrexate has 12 (also Celecoxib, Diflunisal, Indomethacin, Meloxicam); Mefenamic Acid has 3 (also Diflunisal, Warfarin).
What mechanism field is on file for Methotrexate and Mefenamic Acid?
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: Methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)); Mefenamic Acid (Nonsteroidal Anti-Inflammatory Drug (NSAID)).
0 major · 12 moderate · 26 minor · 38 total
- Other moderate peers for Methotrexate
- Celecoxib
- Diflunisal
- Indomethacin
- Meloxicam
0 major · 3 moderate · 12 minor · 15 total
- Other moderate peers for Mefenamic Acid
- Diflunisal
- Warfarin
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.