Ketorolac and Methotrexate interaction
Ketorolac and Methotrexate: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Methotrexate (Xatmep) label · effective 2026-05-28
Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] .
NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), Aspirin, and Steroids Concomitant 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.
Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP.
Despite the potential interactions, studies of methotrexate in patients with rheumatoid arthritis, including patients with polyarticular juvenile idiopathic arthritis (pJIA), have usually included concurrent use of constant dosage regimens of NSAIDs, without apparent problems.
From the Ketorolac (Ketorolac Tromethamine) label · effective 2024-12-31
This may indicate that they could enhance the toxicity of methotrexate.
Caution should be used when NSAIDs are administered concomitantly with methotrexate.
Methotrexate NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices.
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Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.