Methotrexate and Indomethacin Interaction

Drug interaction information between Methotrexate and Indomethacin.

Methotrexate and Indomethacin have a documented moderate interaction in FDA labeling.

FDA drug labeling documents a moderate-severity interaction between Methotrexate and Indomethacin. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.

Drug A

Methotrexate

Disease-Modifying Antirheumatic Drug (DMARD)

Drug B

Indomethacin

Nonsteroidal Anti-Inflammatory Drug (NSAID)

How They Interact

Indomethacin can cause methotrexate to build up to dangerous levels in your body, which may harm your kidneys or blood cells.

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 indomethacin capsules and methotrexate, monitor patients for methotrexate toxicity.

Methotrexate Also Interacts With

View all Methotrexate interactions →

Indomethacin Also Interacts With

View all Indomethacin interactions →

Frequently Asked Questions

What SPL severity band is on file for Methotrexate + Indomethacin?

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 Indomethacin's 35. In the moderate band specifically: Methotrexate has 12 (also Celecoxib, Diflunisal, Mefenamic Acid, Meloxicam); Indomethacin has 5 (also Diflunisal, Heparin, Perindopril, Warfarin).

What mechanism field is on file for Methotrexate and Indomethacin?

Indomethacin can cause methotrexate to build up to dangerous levels in your body, which may harm your kidneys or blood cells.

Methotrexate's labeled portfolio outnumbers Indomethacin

SPL source-record counts only. This page's band is moderate · classes on file: Methotrexate (Disease-Modifying Antirheumatic Drug (DMARD)); Indomethacin (Nonsteroidal Anti-Inflammatory Drug (NSAID)).

Methotrexate

0 major · 12 moderate · 26 minor · 38 total

Indomethacin

0 major · 5 moderate · 30 minor · 35 total

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.