Methotrexate and NSAIDs

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