Indomethacin and Diflunisal Interaction
Drug interaction information between Indomethacin and Diflunisal.
Indomethacin and Diflunisal have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Indomethacin 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
Diflunisal causes the body to have much higher levels of indomethacin in the blood. This increases the risk of serious stomach bleeding without making the medicine work any better.
FDA Label Information
NSAIDs and Salicylates Clinical Impact: Concomitant use of indomethacin 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 ) ] . Combined use with diflunisal may be particularly hazardous because diflunisal causes significantly higher plasma levels of indomethacin [ see Clinical Pharmacology ( 12.3 ) ]. In some patients, combined use of indomethacin and diflunisal has been associated with fatal gastrointestinal hemorrhage.
Indomethacin Also Interacts With
- Methotrexate moderate
- Heparin moderate
- Perindopril moderate
- Warfarin moderate
- Meloxicam minor
Diflunisal Also Interacts With
- Methotrexate moderate
- Cyclosporine moderate
- Celecoxib moderate
- Mefenamic Acid moderate
- Meloxicam moderate
Frequently Asked Questions
What SPL severity band is on file for Indomethacin + 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?
Indomethacin has 35 labeled pairs on file vs Diflunisal's 17. In the moderate band specifically: Indomethacin has 5 (also Methotrexate, Heparin, Perindopril, Warfarin); Diflunisal has 11 (also Methotrexate, Cyclosporine, Celecoxib, Mefenamic Acid).
What mechanism field is on file for Indomethacin and Diflunisal?
Diflunisal causes the body to have much higher levels of indomethacin in the blood. This increases the risk of serious stomach bleeding without making the medicine work any better.
Indomethacin's labeled portfolio outnumbers Diflunisal
SPL source-record counts only. This page's band is moderate · classes on file: Indomethacin (Nonsteroidal Anti-Inflammatory Drug (NSAID)); Diflunisal (Nonsteroidal Anti-Inflammatory Drug (NSAID)).
0 major · 5 moderate · 30 minor · 35 total
- Other moderate peers for Indomethacin
- Methotrexate
- Heparin
- Perindopril
- Warfarin
0 major · 11 moderate · 6 minor · 17 total
- Other moderate peers for Diflunisal
- Methotrexate
- Cyclosporine
- Celecoxib
- 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.