What the FDA labels say about taking them together
Ketorolac and methotrexate
Ketorolac's FDA label (Sprix) of December 5, 2024 names methotrexate in its drug interactions section; methotrexate's label does not name ketorolac itself but warns about its class (NSAIDs (nonsteroidal anti-inflammatory drugs)). The ketorolac label: “Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity.”
Check it at the source: the ketorolac FDA label on DailyMed (effective August 31, 2023, Fresenius Kabi USA, LLC); the methotrexate FDA label on DailyMed (effective May 27, 2026, Accord Healthcare Inc.).
What does the ketorolac label say about methotrexate?
Sprix label (Zyla Life Sciences US LLC, December 5, 2024), drug interactionsMethotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (…). Intervention: During concomitant use of SPRIX and methotrexate, monitor patients for methotrexate toxicity.
Source: FDA drug label (Sprix, NDA022382), Zyla Life Sciences US LLC, effective December 5, 2024 (SPL set 97005a1c-167e-4676-bae7-e49b38c36f9e), via openFDA
Source: FDA drug label (Ketorolac Tromethamine), Fresenius Kabi USA, LLC, effective August 31, 2023 (SPL set 3d88cbe6-5230-47aa-80af-0c41283d1f00), via openFDA; the full label on DailyMed
What does the methotrexate label say about ketorolac?
Methotrexate's label does not name ketorolac 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
| Ketorolac | Methotrexate | |
|---|---|---|
| Labeled for | Pain | Rheumatoid arthritis, Psoriasis, Leukemia, lymphoma and myeloma, Breast cancer |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $1.02 per mL 30 mg/mL vial | $0.158 per tablet 2.5 mg tablet |
| Shortage now | In shortage | 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