Trimethoprim/sulfamethoxazole (TMP/SMX) in combination with drugs that increase potassium

Trimethoprim-sulfamethoxazole (TMP/SMX) can induce hyperkalemia in patients receiving drugs that increase potassium like ACEI or ARBs or aldosterone.
Abdelwahab Ward, BS Pharm, PharmD

As a pharmacist, you should be careful when using trimethoprim/sulfamethoxazole (Bactrim, Septrin, etc.) in combination with drugs that increase potassium like angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), or spironolactone. Remember that trimethoprim/sulfamethoxazole labeling has a precaution about hyperkalemia, and it happens more often than previously recognized. Trimethoprim can decrease urinary potassium excretion because it acts like the potassium-sparing diuretic spironolactone or amiloride.

Potassium can go up in anyone. But hyperkalemia is mainly a problem with high doses, renal insufficiency, or when trimethoprim/sulfamethoxazole (TMP/SMX) is used with other drugs that can increase potassium. New evidence suggests that patients over age 65 are about 7 times more likely to be hospitalized for hyperkalemia if they take trimethoprim/sulfamethoxazole (TMP/SMX) with an ACE inhibitor or ARB. Watch for this interaction.

Hyperkalemia often occurs within 5 days of starting TMP/SMX. Suggest checking potassium on day 4 in patients who will take TMP/SMX longer than 5 days and who are at higher risk for hyperkalemia. These are patients taking TMP/SMX in combination with ACEIs, ARBs, aldosterone antagonists, potassium-sparing diuretics, or potassium supplements. Also, caution about patients with impaired renal function or those taking high doses for MRSA or Pneumocystis pneumonia. Or suggest another antibiotic such as doxycycline or clindamycin for community-acquired methicillin-resistant Staph aureus. Also, use a lower dose for renal insufficiency (CrCl < 30 mL/min). Advise patients on medications that increase potassium to be careful about salt substitutes; they can contain a lot of potassium.

References

  1. Ho JM, Juurlink DN. Considerations when prescribing trimethoprim-sulfamethoxazole. CMAJ. 2011 Nov 8;183(16):1851-8.
  2. Antoniou, T. (2010). Trimethoprim-Sulfamethoxazole–Induced Hyperkalemia in Patients Receiving Inhibitors of the Renin-Angiotensin System. Archives of Internal Medicine, [online] 170(12), p.1045.
  3. Alappan, R. (1996). Hyperkalemia in Hospitalized Patients Treated with Trimethoprim-Sulfamethoxazole. Annals of Internal Medicine, 124(3), p.316.
Abdelwahab Ward, BS Pharm, PharmD