Methotrexate and trimethoprim-sulfamethoxazole: toxicity from this combination continues to occur.

Methotrexate (MTX) is a folic acid antagonist and cell cycle–specific antimetabolite. While still an important component of hematologic and solid tumour treatment regimens, MTX is now used in low doses for the treatment of many autoimmune disorders, including Crohn disease, rheumatoid arthritis, and psoriasis. Although MTX is generally well tolerated at low doses, serious and predictable organ toxicity, including myelosuppression, mucositis, hepatotoxicity, and kidney injury, can occur owing to drug interactions or changes in renal or hepatic function. This toxicity can be rapid and life threatening, even in patients taking oral doses as low as 5 to 25 mg of MTX per week.1 Trimethoprim-sulfamethoxazole (TMP-SMX) is a bacteriostatic antimicrobial used in the treatment and prevention of various infections, including urinary tract infections, otitis media, chronic bronchitis exacerbations, and Pneumocystis jiroveci pneumonia. Like MTX, TMP-SMX is an inhibitor of folic acid metabolism and can cause bone marrow suppression. Trimethoprimsulfamethoxazole is also known to decrease the renal excretion of MTX. When used in combination, the potential for toxicity is substantial. In this article, we report a clinically important interaction between MTX and TMP-SMX that resulted in severe mucositis, pancytopenia, and febrile neutropenia in a patient with Crohn disease who had been treated with long-term, low-dose MTX.