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Methotrexate and NSAIDs

Authoring team

Renal toxicity

 

  • taking methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, or naproxen together can increase the risk of renal toxicity

 

NSAIDs and Methotrexate toxicity

 

  • taking methotrexate and NSAIDs can increase the risk of methotrexate toxicity
    • due to reduced renal elimination
    • risks of this interaction are greater at high doses of methotrexate and in those with pre-existing renal impairment

 

Suggested management options (1):

 

  • use NSAIDs in combination with methotrexate with caution on the advice of the specialist (for example, rheumatologist)
    • aspirin given as an antiplatelet can be continued in people taking methotrexate (1)
    • routine monitoring of methotrexate should detect any signs of methotrexate toxicity.
  • ensure you counsel people taking methotrexate to avoid buying NSAIDs over-the-counter (e.g. oral ibuprofen or analgesic doses of aspirin) without discussing with their doctor or pharmacist first
  • counsel the person to report signs of methotrexate toxicity, for example sore throat, mouth ulcers, unexplained bruising or bleeding

Reference:

  1. NHS Specialist Pharmacy Service (June 30th 2025). Managing interactions with methotrexate

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