Naproxen and Diflunisal Interaction
Drug interaction information between Naproxen and Diflunisal.
Naproxen and Diflunisal have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Naproxen and Diflunisal. 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
Taking these two similar pain relievers together increases the risk of stomach and intestinal damage without providing extra relief.
FDA Label Information
NSAIDs and Salicylates Clinical Impact: Concomitant use of naproxen with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [ see Warnings and Precautions ( 5.2 ) ].
Naproxen Also Interacts With
- Methotrexate moderate
- Magnesium Oxide moderate
- Sucralfate moderate
- Cholestyramine moderate
- Meloxicam minor
Diflunisal Also Interacts With
- Methotrexate moderate
- Cyclosporine moderate
- Celecoxib moderate
- Indomethacin moderate
- Mefenamic Acid moderate
Frequently Asked Questions
What SPL severity band is on file for Naproxen + Diflunisal?
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?
Naproxen has 23 labeled pairs on file vs Diflunisal's 17. In the moderate band specifically: Naproxen has 5 (also Methotrexate, Magnesium Oxide, Sucralfate, Cholestyramine); Diflunisal has 11 (also Methotrexate, Cyclosporine, Celecoxib, Indomethacin).
What mechanism field is on file for Naproxen and Diflunisal?
Taking these two similar pain relievers together increases the risk of stomach and intestinal damage without providing extra relief.
Naproxen's labeled portfolio outnumbers Diflunisal
SPL source-record counts only. This page's band is moderate · classes on file: Naproxen (Nonsteroidal Anti-Inflammatory Drug (NSAID)); Diflunisal (Nonsteroidal Anti-Inflammatory Drug (NSAID)).
0 major · 5 moderate · 18 minor · 23 total
- Other moderate peers for Naproxen
- Methotrexate
- Magnesium Oxide
- Sucralfate
- Cholestyramine
0 major · 11 moderate · 6 minor · 17 total
- Other moderate peers for Diflunisal
- Methotrexate
- Cyclosporine
- Celecoxib
- Indomethacin
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.