Caution with TMP/SMX and Potassium-Increasing Drugs

As a pharmacist, exercise caution when using trimethoprim/sulfamethoxazole (Bactrim, Septrin, etc.) with drugs that increase potassium (K⁺) levels, such as ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or spironolactone. TMP/SMX can cause hyperkalemia, which is more common than previously thought, by decreasing urinary K⁺ excretion, similar to K⁺-sparing diuretics.

• Hyperkalemia risk increases with high doses, renal insufficiency, or use with other K⁺-increasing drugs.
• Patients over 65 are 7 times more likely to be hospitalized for hyperkalemia if taking TMP/SMX with an ACEI or ARB.
• Hyperkalemia often occurs within 5 days of starting TMP/SMX.

Monitor for this interaction. Check K⁺ levels on day 4 in patients taking TMP/SMX for more than 5 days and at higher risk. High-risk groups include those on ACEIs, ARBs, aldosterone antagonists, K⁺-sparing diuretics, K⁺ supplements, impaired renal function, or high doses for MRSA or Pneumocystis pneumonia. Consider alternatives like doxycycline or clindamycin for community-acquired MRSA. Use a lower TMP/SMX dose for renal insufficiency (CrCl < 30 mL/min). Advise patients on K⁺-increasing medications to avoid salt substitutes high in K⁺.

Take-home points

1. Use TMP/SMX carefully with ACEIs, ARBs, or spironolactone due to hyperkalemia risk.
2. Patients over 65 have higher hyperkalemia hospitalization rates with TMP/SMX plus ACEIs/ARBs.
3. Check K⁺ levels on day 4 for high-risk patients on TMP/SMX for more than 5 days.
4. High-risk patients include those on ACEIs, ARBs, aldosterone antagonists, K⁺-sparing diuretics, K⁺ supplements, or with renal insufficiency.
5. Consider alternative antibiotics such as doxycycline or clindamycin for community-acquired MRSA.
6. Use a lower TMP/SMX dose for CrCl < 30 mL/min.
7. Warn patients about K⁺ content in salt substitutes.

References

Keywords: Trimethoprim/sulfamethoxazole (TMP/SMX), hyperkalemia risk, potassium levels, ACE inhibitors (ACEIs), ARBs interactions, spironolactone caution, K⁺-sparing diuretics, renal insufficiency, elderly hyperkalemia, MRSA treatment.