Drug Interaction Between Methotrexate And Naproxen

The pharmacist discusses the interaction between methotrexate and NSAIDs like naproxen.

Jul 13, 2018

Patti asked

Can I take naproxen while I am taking methotrexate?

Answer

In general, NSAIDs (non-steroidal anti-inflammatory drugs) like naproxen should not be taken at the same time as methotrexate as the combination may cause serious side effects when used together. Besides naproxen, other NSAIDs include:

  • Ibuprofen
  • Celebrex (celecoxib)
  • Mobic (meloxicam)
  • Feldene (piroxicam)
  • Voltaren (diclofenac)

However, as is discussed below, the use of NSAIDs may be safe in those who are taking low doses of methotrexate for certain conditions, such as rheumatoid arthritis.

Interaction Between NSAIDs And Methotrexate

In general, NSAIDs can decrease the clearance of methotrexate, resulting in elevated and prolonged methotrexate levels in the body. In most cases, NSAIDs should not be administered prior to, concomitantly, or following intermediate or high doses of methotrexate.

Concomitant administration of NSAIDs with high dose methotrexate therapy (e.g. for the treatment of cancer) has been reported to elevate and prolong serum concentrations of methotrexate in the body, resulting in deaths from severe hematologic and gastrointestinal toxicity. 

However, it is important to note that when methotrexate is used in patients with rheumatoid arthritis, it has been given at the same time as NSAIDs with few, if any, problems. This is because the doses of methotrexate used in rheumatoid arthritis are lower than those used in psoriasis or malignant disease. Nevertheless, higher methotrexate doses may lead to unexpected toxicity in combination with NSAIDs. Therefore, while NSAIDs have been used safely in those who take low doses of methotrexate, caution should be used either way.

Lastly, methotrexate increases the risk of infection due to suppression of the immune system. Use of NSAIDs may mask fever, pain, swelling and other signs and symptoms of an infection. It is important to not use NSAIDs like naproxen with methotrexate without checking with your doctor first.

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