Etodolac and Methotrexate Interaction

Drug interaction information between Etodolac and Methotrexate.

Etodolac and Methotrexate have a documented minor interaction in FDA labeling.

FDA drug labeling documents a minor-severity interaction between Etodolac 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.

Drug A

Etodolac

Nonsteroidal Anti-Inflammatory Drug (NSAID)

Drug B

Methotrexate

Disease-Modifying Antirheumatic Drug (DMARD)

How They Interact

Etodolac can slow down how fast your kidneys remove methotrexate from your body, which causes the drug to build up to unsafe levels. This buildup can make the side effects of methotrexate more dangerous.

FDA Label Information

Cyclosporine, Digoxin, Methotrexate Etodolac, like other NSAIDs, through effects on renal prostaglandins, may cause changes in the elimination of these drugs leading to elevated serum levels of cyclosporine, digoxin, methotrexate, and increased toxicity. NSAIDs, such as etodolac, should not be administered prior to or concomitantly with high doses of methotrexate. NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices.

Methotrexate Also Interacts With

View all Methotrexate interactions →

Frequently Asked Questions

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

Compiled FDA labeling labels this pair minor. 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 Etodolac's 10. In the minor band specifically: Etodolac has 9 (also Hydrochlorothiazide, Furosemide, Aspirin, Cyclosporine); Methotrexate has 26 (also Aspirin, Folic Acid, Probenecid, Phenytoin).

What mechanism field is on file for Etodolac and Methotrexate?

Etodolac can slow down how fast your kidneys remove methotrexate from your body, which causes the drug to build up to unsafe levels. This buildup can make the side effects of methotrexate more dangerous.

Methotrexate's labeled portfolio outnumbers Etodolac

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

Etodolac

0 major · 1 moderate · 9 minor · 10 total

Methotrexate

0 major · 12 moderate · 26 minor · 38 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.