What the FDA labels say about taking them together
Ibuprofen and methotrexate
Ibuprofen's FDA label of January 1, 2026 names methotrexate in its drug interactions (prescription label) section; methotrexate's label does not name ibuprofen itself but warns about its class (NSAIDs (nonsteroidal anti-inflammatory drugs)). The ibuprofen label: “Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity.”
Check it at the source: the ibuprofen FDA label on DailyMed (effective January 1, 2026, Savings Distributors LLC); the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.).
What does the ibuprofen label say about methotrexate?
Ibuprofen label, drug interactions (prescription label)Thus, when ibuprofen and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. (Read circulars for lithium preparation before use of such concurrent therapy.) Methotrexate NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices.
Caldolor label (Cumberland Pharmaceuticals Inc., January 29, 2026), drug interactionsMethotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (…). Intervention: During concomitant use of CALDOLOR and methotrexate, monitor patients for methotrexate toxicity.
Source: FDA drug label (Caldolor, NDA022348), Cumberland Pharmaceuticals Inc., effective January 29, 2026 (SPL set 1eaa7790-f1a1-4f51-b10a-cbbaf033f684), via openFDA
Source: FDA drug label (Motrin IB), NDA019012 (Kenvue Brands), as published by Savings Distributors LLC, effective January 1, 2026 (SPL set 56846774-8413-c306-e063-6394a90a2be8), via openFDA; the full label on DailyMed
What does the methotrexate label say about ibuprofen?
Methotrexate's label does not name ibuprofen 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
| Ibuprofen | Methotrexate | |
|---|---|---|
| Labeled for | Fever, Osteoarthritis, Rheumatoid arthritis, Pain, Cough and cold | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $0.0573 per tablet 800 mg tablet | $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