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June 28, 2016

Interactions of methotrexate and non-steroidal anti-inflammatory drugs

Coadministration of methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) can cause a pharmacokinetic interaction and a subsequent increase in blood methotrexate concentrations.

NSAID-induced increases in methotrexate concentrations are due to:

  • Decreased glomerular filtration of methotrexate by NSAIDs via the reduction of renal blood flow with inhibition of prostaglandin synthesis.
  • Inhibition of methotrexate tubular secretion.
  • Competition for protein-binding sites.

NSAIDs should not be administered before or concurrently with high-dose methotrexate. Concomitant use of some NSAIDs and high-dose methotrexate has been reported to increase and prolong the serum methotrexate concentration in serum and to increase gastrointestinal and haematological toxicity.

However, patients with rheumatoid arthritis have generally been treated without problems with NSAIDs in addition to methotrexate. It should be noted, that the doses of methotrexate used in the treatment of rheumatoid arthritis (7.5- 15mg/week) are slightly lower than those used for psoriasis and that higher doses can result in unexpected toxicity.

If concomitant treatment with NSAIDs is commenced, methotrexate dosage should be monitored.


1- Methotrexate Summary of Product Characteristics. Revised december 2009.

2- Maeda A. et al. Evaluation of the interaction between nonsteroidal anti-inflammatory drugs and methotrexate using human organic anion transporter 3-transfected cells. Eur J Pharmacol. 2008. Oct 31; 596(1-3):166-72.