AS A PHARMACIST, you will hear more about possible harm when TMP/SMX (Bactrim, Septrin, Septazole, etc) is combined with medications that increase potassium (ACEIs, spironolactone, etc). This interaction is more risky than previously thought and is popping up on more drug interaction software.
Trimethoprim decreases urinary excretion of potassium. Up to 6% of patients on TMP/SMX develop hyperkalemia and the risk is higher when it's added to other medications that raise potassium like ACEIs, ARBs, aldosterone antagonists and potassium supplements, etc.
Hospitalizations due to hyperkalemia increase by 7-fold or more when seniors take TMP/SMX with an ACEI, ARB, or spironolactone. And about 3 of every 1000 seniors will have sudden death within 14 days of taking an ACEI or ARB with TMP/SMX compared to one of every 1000 patients on an ACEI or ARB with amoxicillin. Hyperkalemia often occurs a few days after starting TMP/SMX. Think twice before prescribing TMP/SMX (Bactrim, Septrin DS, Septazole, etc) to patients taking another medication that increases potassium especially when using longer than a 3-day course.
Be especially vigilant in patients at high risk due to age ≥ 65, renal insufficiency, diabetes, heart failure, or those taking more than one other medication that raises potassium. If needed, switch antibiotics, check potassium after 4 or 5 days of TMP/SMX or possibly hold the ACEI, etc.
REFERENCES
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Fralick M, Macdonald EM, Gomes T, Antoniou T, Hollands S, Mamdani MM, Juurlink DN; Canadian Drug Safety and Effectiveness Research Network. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. BMJ. 2014 Oct 30;349:g6196. Available at: https://www.bmj.com/content/349/bmj.g6196.long
Antoniou T, Gomes T, Mamdani MM, Yao Z, Hellings C, Garg AX, Weir MA, Juurlink DN. Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study. BMJ. 2011 Sep 12;343:d5228. Available at: https://www.bmj.com/content/343/bmj.d5228.long