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Mefenamic Acid and Methotrexate Interaction

Drug interaction information between Mefenamic Acid and Methotrexate.

Mefenamic Acid and Methotrexate have a documented moderate interaction in FDA labeling.

FDA drug labeling documents a moderate-severity interaction between Mefenamic Acid 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

Mefenamic Acid

Nonsteroidal Anti-Inflammatory Drug (NSAID)

Drug B

Methotrexate

Disease-Modifying Antirheumatic Drug (DMARD)

How They Interact

This pain medicine can prevent your body from clearing out methotrexate, which can lead to toxic levels in your system.

What To Do

Your doctor should monitor you for signs of toxicity, such as kidney issues or changes in your blood cell counts.

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 mefenamic acid and methotrexate, monitor patients for methotrexate toxicity.

Mefenamic Acid Also Interacts With

View all Mefenamic Acid interactions →

Methotrexate Also Interacts With

View all Methotrexate interactions →

Frequently Asked Questions

Can I take Mefenamic Acid and Methotrexate together?

This is a moderate interaction. Your doctor should monitor you for signs of toxicity, such as kidney issues or changes in your blood cell counts.

How serious is the interaction between Mefenamic Acid 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 Mefenamic Acid and Methotrexate interact?

This pain medicine can prevent your body from clearing out methotrexate, which can lead to toxic levels in your system.

Understanding the Mefenamic Acid and Methotrexate Interaction

FDA-approved prescribing information for these two drugs flags their combination as a moderate-severity interaction. Mefenamic Acid 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: This pain medicine can prevent your body from clearing out methotrexate, which can lead to toxic levels in your system. 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. Mefenamic Acid has 15 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 for signs of toxicity, such as kidney issues or changes in your blood cell counts. 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 Mefenamic Acid 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.