Indomethacin and Methotrexate Interaction
Drug interaction information between Indomethacin and Methotrexate.
Indomethacin and Methotrexate have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Indomethacin 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.
How They Interact
Indomethacin can cause methotrexate to build up to dangerous levels in your body, which may harm your kidneys or blood cells.
What To Do
Your doctor should monitor you closely for signs of drug toxicity while you are using both medications.
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.
Indomethacin Also Interacts With
- Diflunisal moderate
- Heparin moderate
- Perindopril moderate
- Warfarin moderate
- Meloxicam minor
Methotrexate Also Interacts With
- Celecoxib moderate
- Diflunisal moderate
- Mefenamic Acid moderate
- Meloxicam moderate
- Misoprostol moderate
Frequently Asked Questions
Can I take Indomethacin and Methotrexate together?
This is a moderate interaction. Your doctor should monitor you closely for signs of drug toxicity while you are using both medications.
How serious is the interaction between Indomethacin and Methotrexate?
This interaction is classified as "moderate" severity by the FDA. Moderate interactions may worsen your condition or change how your medications work.
Why do Indomethacin and Methotrexate interact?
Indomethacin can cause methotrexate to build up to dangerous levels in your body, which may harm your kidneys or blood cells.
Understanding the Indomethacin and Methotrexate Interaction
FDA-approved prescribing information for these two drugs flags their combination as a moderate-severity interaction. Indomethacin 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: Indomethacin can cause methotrexate to build up to dangerous levels in your body, which may harm your kidneys or blood cells. 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. Indomethacin has 35 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: Your doctor should monitor you closely for signs of drug toxicity while you are using both medications. 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 Indomethacin 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.
Read our methodology - how this data is sourced, computed, and verified.