Trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jirovecii pneumonia (PCP) prophylaxis in combination with methotrexate (MTX) was shown to be successful and well-tolerated in patients with chronic inflammatory/autoimmune diseases, according to data published in Journal of the American Academy of Dermatology.

A common treatment for chronic inflammatory and autoimmune diseases is MTX. Patients taking MTX who are older, with lymphopenia and/or parenchymal lung disease, and/or taking additional immunosuppressive medications, a prophylaxis against PCP is often recommended. TMP-SMX is a front-line PCP treatment, but it is relatively contraindicated in patients taking MTX due to synergistic toxicities.

To investigate the safety of TMP-SMX dosing for PCP prophylaxis in combination with patients receiving MTX, researchers performed a retrospective review. Included patients had been prescribed TMP-SMX for PCP prophylaxis concurrently with MTX for >1 month in 2017. The first 100 patients with > 1 set of complete blood counts (CBCs) and complete metabolic panels (CMPs) during combination therapy were included.

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Of these 100 patients, 6% experienced adverse events resulting in discontinuation of therapy. Reasons for discontinuation included transaminitis (n=4) and/or leukopenia (n=2). No patients contracted PCP or had an adverse event that led to end-organ damage. Those with adverse events triggering discontinuation were on average 8.5 years younger than those who did not (P = .03). Adverse events were not significantly associated with MTX dose, treatment duration and folic acid/ leucovorin dose.

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According to investigators, “our findings suggest baseline CBCs and CMPs may be useful in identifying at-risk patients for adverse effects if placed on MTX and TMP-SMX combination therapy.” The study was however limited by a relatively small sample size from a single U.S. academic center.

It was concluded that, “combination MTX and PCP prophylaxis dosed TMP-SMX therapy appears both successful and well-tolerated in patients with chronic inflammatory/autoimmune diseases.” Investigators recommended alternative PCP prophylaxis strategies for patients with underlying liver and/or CBC abnormalities. They also stressed that due to potential adverse effects both CBCs and CMPs should be monitored closely before and during combination therapy.


Havele SA, Ellis A, Chaitoff A, et al. Safety of trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis in patients taking methotrexate [published April 19 2020]. J Am Acad Dermatol. doi:10.1016/j.jaad.2020.04.040

This article originally appeared on Infectious Disease Advisor