What the FDA labels say about taking them together
Mefenamic acid and methotrexate
Mefenamic acid's FDA label of April 20, 2026 names methotrexate in its drug interactions section; methotrexate's label does not name mefenamic acid itself but warns about its class (NSAIDs (nonsteroidal anti-inflammatory drugs)). The mefenamic acid label: “Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity.”
Check it at the source: the mefenamic acid FDA label on DailyMed (effective April 20, 2026, Lupin Pharmaceuticals, Inc.); the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.).
What does the mefenamic acid label say about methotrexate?
Mefenamic acid label, drug interactionsMethotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (…). Intervention: During concomitant use of mefenamic acid and methotrexate, monitor patients for methotrexate toxicity.
Source: FDA drug label (Mefenamic Acid), Lupin Pharmaceuticals, Inc., effective April 20, 2026 (SPL set d15733a9-d5fd-4d5f-86ce-e7ed8c706c7f), via openFDA; the full label on DailyMed
What does the methotrexate label say about mefenamic acid?
Methotrexate's label does not name mefenamic acid itself; it warns about its class (NSAIDs (nonsteroidal anti-inflammatory drugs)):
Methotrexate label, boxed warningUnexpectedly severe (sometimes fatal) bone marrow suppression, aplastic anemia, and gastrointestinal toxicity have been reported with concomitant administration of methotrexate (usually in high dosage) along with some nonsteroidal anti-inflammatory drugs (NSAIDs) [see Warnings and Precautions (5.1) and Drug Interactions(7.1) ].
Methotrexate label, drug interactionsConcomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity [see Warnings and Precautions (5.1) ].
Source: FDA drug label (Methotrexate), Accord Healthcare Inc., effective May 27, 2026 (SPL set 874c7f43-a3be-4236-89cc-24c44e3c5813), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Mefenamic acid | Methotrexate | |
|---|---|---|
| Labeled for | Pain | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $0.948 per capsule 250 mg capsule | $0.158 per tablet 2.5 mg tablet |
| Shortage now | No current entry | In shortage |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once