Prescriptions for a Toxic Combination: Use of Methotrexate Plus Trimethoprim-Sulfamethoxazole in the United States

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To determine the frequency of using the potentially toxic combination of methotrexate and trimethoprim-sulfamethoxazole (TMP-SMX) in outpatient practice in the United States.


Data from the National Ambulatory Medical Care Survey for 1993–2010 were used to assess the frequency of using methotrexate with TMP-SMX and associated physician specialties and diagnoses.


TMP-SMX was coprescribed in 22,000 methotrexate visits per year (1.0% of methotrexate visits). Pediatricians prescribed the combination most frequently, and the most common diagnosis was acute lymphoblastic leukemia. There was no significant change over time in coprescription of TMP-SMX with methotrexate (P = 0.4).


Low-dose TMP-SMX with methotrexate chemotherapy appears to be standard for patients with acute lymphoblastic leukemia; however, other uses appear questionable, and clinicians should be cognizant of the risk for fatal interactions, especially when medications are prescribed by multiple providers.

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