Celecoxib and Methotrexate interaction

Celecoxib 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.

Major

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

Major

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 )] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity.

Drug interactionsby drug classView label on DailyMed
Moderate

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.

Drug interactionsby drug classView label on DailyMed
Moderate

Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP.

Drug interactionsby drug classView label on DailyMed
Moderate

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.

Drug interactionsby drug classView label on DailyMed

From the Celecoxib (VYSCOXA) label · effective 2025-07-31

Moderate

Methotrexate Clinical Impact: Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).

Drug interactionsnames MethotrexateView label on DailyMed
Moderate

Intervention: During concomitant use of VYSCOXA and methotrexate, monitor patients for methotrexate toxicity.

Drug interactionsnames MethotrexateView label on DailyMed
No interaction

Celecoxib has no effect on methotrexate pharmacokinetics.

Drug interactionsnames MethotrexateView label on DailyMed

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Not 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.