Trimethoprim-sulfamethoxazole induces reversible hyperkalemia

Ann Intern Med. 1993 Aug 15;119(4):291-5. doi: 10.7326/0003-4819-119-4-199308150-00007.


Objective: To determine the effect of trimethoprimsulfamethoxazole (Tmp-Smx) on serum potassium concentration.

Design: Retrospective cohort study.

Setting: An urban teaching hospital.

Patients: Fifty-one persons hospitalized for symptomatic infection with human immunodeficiency virus (HIV). Twenty-five patients who were taking high-dose Tmp-Smx (trimethoprim 20 mg/kg per day; sulfamethoxazole, 100 mg/kg per day) for Pneumocystis carinii pneumonia were the study group. Twenty-six patients who had not received the drug were the control group. Patients who received potassium supplements, those taking medications known to alter potassium homeostasis or renal function, or those with a serum creatinine level more than 186 mumol/L were excluded.

Measurements and main results: Serum potassium concentration in the study group was 4.1 +/- 0.1 mmol/L (mean +/- SE) and increased by 1.1 mmol/L (Cl, 0.8 to 1.5 mmol/L) (P < 0.0001) 9.8 +/- 0.5 days after starting Tmp-Smx therapy. Patients followed longitudinally showed a progressive increase in serum potassium levels during therapy and a progressive decline after discontinuing Tmp-Smx. Blood urea nitrogen and serum creatinine levels increased mildly from 4.3 +/- 0.5 mmol/L and 85 +/- 6 mumol/L to 6.4 +/- 0.7 mmol/L and 113 +/- 8 mumol/L, respectively. The serum potassium level in the control group was 4.3 +/- 0.1 mmol/L and remained unchanged during hospitalization.

Conclusions: High-dose Tmp-Smx therapy used for the treatment of P. carinii pneumonia in HIV-infected patients leads to an increase in the serum potassium concentration and may result in life-threatening hyperkalemia. Patients receiving high doses of Tmp-Smx require close monitoring of their serum potassium concentration, particularly 7 to 10 days after the start of therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • Adult
  • Cohort Studies
  • Female
  • Humans
  • Hyperkalemia / blood
  • Hyperkalemia / chemically induced*
  • Male
  • Middle Aged
  • Pneumonia, Pneumocystis / drug therapy*
  • Retrospective Studies
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects*
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use


  • Trimethoprim, Sulfamethoxazole Drug Combination