What the FDA labels say about taking them together
Aspirin and methotrexate
Methotrexate's FDA label of May 27, 2026 names aspirin in its drug interactions section; the aspirin label PlainMeds reads does not name methotrexate. The methotrexate label: “DRUG INTERACTIONS Aspirin, NSAIDs, and steroids: concomitant use may elevate and prolong serum methotrexate levels and cause increased toxicity.”
Check it at the source: the aspirin FDA label on DailyMed (effective September 9, 2025); the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.).
What does the aspirin label say about methotrexate?
Aspirin's label (effective September 9, 2025) does not name methotrexate in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (Medique Products Aspirin), Unifirst First Aid Corporation, effective September 9, 2025 (SPL set 9b28fed0-a993-ca72-e053-2995a90ac7fd), via openFDA; the full label on DailyMed
What does the methotrexate label say about aspirin?
Methotrexate label, drug interactionsOral antibiotics (including neomycin) Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Oral or intravenous penicillin or sulfonamide antibiotics Aspirin and other nonsteroidal anti-inflammatory drugs Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Hepatotoxic products Proton pump inhibitors Weak acids (e.g., salicylates) Nephrotoxic products Probenecid Nitrous Oxide Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions.
Rasuvo label (Medexus Pharma Inc., December 15, 2025), drug interactionsDRUG INTERACTIONS Aspirin, NSAIDs, and steroids: concomitant use may elevate and prolong serum methotrexate levels and cause increased toxicity ( 7.1 ) Proton pump inhibitors: concomitant use may elevate and prolong serum methotrexate levels and cause increased toxicity
Methotrexate label (Hospira, Inc., August 22, 2025), drug interactionsAspirin and other nonsteroidal anti-inflammatory drugs Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of methotrexate (primarily at high-dose) and nonsteroidal anti-inflammatory drugs (NSAIDs).
Otrexup label (Antares Pharma, Inc., January 31, 2025), drug interactionsDRUG INTERACTIONS Aspirin, NSAIDs, and steroids: concomitant use may elevate and prolong serum methotrexate levels and cause increased toxicity ( 7.1 ).
Source: FDA drug label (Rasuvo, NDA205776), Medexus Pharma Inc., effective December 15, 2025 (SPL set d0075461-0e7e-4967-9c9b-d6440e912c0e), via openFDA
Source: FDA drug label (Methotrexate, NDA011719), Hospira, Inc., effective August 22, 2025 (SPL set 0e30eaef-5a09-4104-8a11-c32933eadeab), via openFDA
Source: FDA drug label (Otrexup, NDA204824), Antares Pharma, Inc., effective January 31, 2025 (SPL set 9ab8ce16-f7de-41d4-a4c8-1c742621b6d5), via openFDA
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
| Aspirin | Methotrexate | |
|---|---|---|
| Labeled for | Pain, Cough and cold, Fever | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer |
| Boxed warning | No | Yes |
| Pharmacy cost (NADAC) | $0.0142 per tablet 81 mg tablet | $0.158 per tablet 2.5 mg tablet |
| Shortage now | A presentation being discontinued | 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