Prophylactic trimethoprim-sulfamethoxazole is safe in adult patients with primary central nervous system lymphoma receiving high-dose methotrexate

This retrospective study investigated the potential drug-drug interactions between trimethoprim-sulfamethoxazole (TMP-SMZ) and high-dose methotrexate (HD-MTX) in adult patients with primary central nervous system lymphoma (PCNSL). A total of 143 Chinese adult patients with PCNSL who received 498 cycles of MTX were included. Differences in the pharmacokinetics of MTX, including Cmax, clearance (CL) and AUC0-48 h with and without co-administration of TMP-SMZ were assessed. The incidence of MTX-related acute kidney injury (AKI), hepatotoxicity, myelosuppression, and delayed MTX elimination at 48 and 72 h were also compared. Patients were divided into two cohorts for analysis: 146 cycles with TMP-SMZ exposure and 352 cycles without TMP-SMZ exposure. Patients who received TMP-SMZ concurrently with HD-MTX exhibited a 1.13-fold increase in Cmax, a 1.12-fold increase in AUC0-48 h and a reduction in CL by 0.87-fold for MTX. There was no significant difference in the incidence of MTX-related AKI, hepatotoxicity, myelosuppression, or delayed MTX elimination between the two cohorts. Prophylactic TMP-SMZ might lead to increased MTX exposure but has no impact on the incidence of myelosuppression, AKI, and hepatotoxicity. These results suggested that prophylactic TMP-SMZ is safe for adult patients with PCNSL receiving HD-MTX.