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


Correspondence: O. M. Al-Quteimat, Pharmaceutical Care Department, King Abdullah Medical City, Makkah, Saudi Arabia. Tel.: +966568493883; fax: +96625549999 ext. 80136; e-mail:


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.


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.