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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. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.

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.

What To Do

Do not take these two medicines together, especially if you are taking a high dose of methotrexate. Your doctor may need to check your blood levels or change your treatment.

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

Can I take Etodolac and Methotrexate together?

This is a minor interaction. Do not take these two medicines together, especially if you are taking a high dose of methotrexate. Your doctor may need to check your blood levels or change your treatment.

How serious is the interaction between Etodolac and Methotrexate?

This interaction is classified as "minor" severity by the FDA. Minor interactions are unlikely to cause significant problems but should still be mentioned to your healthcare provider.

Why do Etodolac and Methotrexate 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.

Understanding the Etodolac and Methotrexate Interaction

FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Etodolac belongs to the Nonsteroidal Anti-Inflammatory Drug (NSAID) class and Methotrexate belongs to the Disease-Modifying Antirheumatic Drug (DMARD) class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Etodolac can slow down how fast your kidneys remove methotrexate from your body, which causes the drug to build up to unsafe levels. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.

Context around a specific patient determines real-world impact. Etodolac has 10 total documented interactions on file in this dataset, and Methotrexate has 38. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Do not take these two medicines together, especially if you are taking a high dose of methotrexate. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.

An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Etodolac or Methotrexate based on a web page, speak with your prescriber or pharmacist before making any change.

Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.