What the FDA labels say about taking them together
Methotrexate and naproxen
Naproxen's FDA label of March 12, 2026 names methotrexate in its drug interactions (prescription label) section; methotrexate's label does not name naproxen itself but warns about its class (NSAIDs (nonsteroidal anti-inflammatory drugs)). The naproxen label: “Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity.”
Check it at the source: the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.); the naproxen FDA label on DailyMed (effective March 12, 2026, Bayer HealthCare LLC.).
What does the methotrexate label say about naproxen?
Methotrexate's label does not name naproxen 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
What does the naproxen label say about methotrexate?
Naproxen label, drug interactions (prescription label)Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (…). Intervention: During concomitant use of naproxen tablets or naproxen sodium tablets and methotrexate, monitor patients for methotrexate toxicity.
Naproxen label (Acella Pharmaceuticals, LLC, January 5, 2026), drug interactionsMethotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (…). Intervention: During concomitant use of Naproxen Suspension and methotrexate, monitor patients for methotrexate toxicity.
Source: FDA drug label (Naprelan, NDA020353), Upsher-Smith Laboratories, LLC, effective January 8, 2026 (SPL set b8a51c9a-488e-4377-a041-436f6a2f8893), via openFDA
Source: FDA drug label (Naproxen, NDA018965), Acella Pharmaceuticals, LLC, effective January 5, 2026 (SPL set 7e6f03fb-4b36-4418-9684-f45637abbb78), via openFDA
Source: FDA drug label (Naproxen, NDA020067), Zameer Pharmaceuticals LLC, effective August 23, 2025 (SPL set d2e5553a-7c90-407c-9f07-3be65560c23a), via openFDA
Source: FDA drug label (Aleve Caplets), Bayer HealthCare LLC., effective March 12, 2026 (SPL set 02941928-128a-2c88-e063-6294a90ac6ba), 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
| Methotrexate | Naproxen | |
|---|---|---|
| Labeled for | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer | Fever, Rheumatoid arthritis, Osteoarthritis, Gout, Pain, Cough and cold |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $0.158 per tablet 2.5 mg tablet | $0.0565 per tablet 500 mg tablet |
| Shortage now | In shortage | No current entry |
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