Naproxen and Methotrexate Interaction
Drug interaction information between Naproxen and Methotrexate.
Naproxen and Methotrexate have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Naproxen 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
Naproxen can cause methotrexate to stay in your system longer, which increases the risk of harmful side effects like low blood cell counts or kidney problems.
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 naproxen tablets or naproxen sodium tablets and methotrexate, monitor patients for methotrexate toxicity.
Naproxen Also Interacts With
- Magnesium Oxide moderate
- Diflunisal moderate
- Sucralfate moderate
- Cholestyramine moderate
- Meloxicam minor
Methotrexate Also Interacts With
- Celecoxib moderate
- Diflunisal moderate
- Indomethacin moderate
- Mefenamic Acid moderate
- Meloxicam moderate
Frequently Asked Questions
What SPL severity band is on file for Naproxen + 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 Naproxen's 23. In the moderate band specifically: Naproxen has 5 (also Magnesium Oxide, Diflunisal, Sucralfate, Cholestyramine); Methotrexate has 12 (also Celecoxib, Diflunisal, Indomethacin, Mefenamic Acid).
What mechanism field is on file for Naproxen and Methotrexate?
Naproxen can cause methotrexate to stay in your system longer, which increases the risk of harmful side effects like low blood cell counts or kidney problems.
Methotrexate's labeled portfolio outnumbers Naproxen
SPL source-record counts only. This page's band is moderate · classes on file: Naproxen (Nonsteroidal Anti-Inflammatory Drug (NSAID)); Methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)).
0 major · 5 moderate · 18 minor · 23 total
- Other moderate peers for Naproxen
- Magnesium Oxide
- Diflunisal
- Sucralfate
- Cholestyramine
0 major · 12 moderate · 26 minor · 38 total
- Other moderate peers for Methotrexate
- Celecoxib
- Diflunisal
- Indomethacin
- Mefenamic Acid
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.