While trimethoprim-sulfamethoxazole  is generally been felt to be well tolerated, a case-control study has shown association between sudden death, possibly due to hyperkalemia, and prescription of TMP-SMX among older patients who were also receiving an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker.

As per the report published in BMJ those who received TMP-SMX had an increased seven-day risk of sudden death compared with those who received amoxicillin.