Methotrexate and trimethoprim-sulphamethoxazole: extremely serious and life-threatening combination

J Clin Pharm Ther. 2013 Jun;38(3):203-5. doi: 10.1111/jcpt.12060. Epub 2013 Mar 22.


What is known and objective: Combining methotrexate (MTX) with trimethoprim-sulfamethoxazole (TS) is associated with a potential drug interaction that increases MTX toxicity. The aim of this article is to review the current literature about the potential drug interaction resulting from combining MTX with TS, and to establish therapeutic recommendations regarding their use together.

Methods: Literature for relevant evidence was searched by Medline (through PubMed), Cochrane library and a manual search through major journals for articles referenced in those located through PubMed.

Results and discussion: One systematic review, three studies and 17 case reports were found to be relevant to the topic. Results from the current available literature clearly indicate a major drug interaction between MTX and TS, which increases the risk of MTX toxicity, like severe pancytopenia, which was fatal in some cases. Recommendations to prevent this serious interaction should be developed and implemented in the currently available therapeutic guidelines related to MTX therapy.

What is new and conclusion: MTX and TS is an extremely serious and life-threatening combination that should be avoided. Practical recommendations regarding MTX use can be established to prevent harm from drug interactions. Increasing awareness of physicians, pharmacist and patients is essential to assure safe and effective MTX therapy.

Publication types

  • Case Reports
  • Review
  • Systematic Review

MeSH terms

  • Anti-Infective Agents / adverse effects
  • Anti-Infective Agents / therapeutic use
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / therapeutic use
  • Drug Interactions
  • Humans
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use*
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects*
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*


  • Anti-Infective Agents
  • Antirheumatic Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Methotrexate