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Trimethoprim-Sulfamethoxazole Induces Reversible Hyperkalemia

Sheldon Greenberg; Ira W. Reiser; Shyan-Yih Chou; and Jerome G. Porush
[+] Article, Author, and Disclosure Information

From Brookdale Hospital Medical Center, Brooklyn, New York. Requests for Reprints: Ira W. Reiser, MD, Division of Nephrology and Hypertension, The Brookdale Hospital Medical Center, Brooklyn, NY 11212. Grant Support: By the National Kidney Foundation of New York/New Jersey.

Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;119(4):291-295. doi:10.7326/0003-4819-119-4-199308150-00007
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Objective: To determine the effect of trimethoprim-sulfamethoxazole (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 mol/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 (CI, 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 mol/L to 6.4 0.7 mmol/L and 113 8 mol/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.


Grahic Jump Location
Figure 1.
Changes in serum potassium concentrations with trimethoprim-sulfamethoxazole therapy.P

Values in 25 patients were obtained at the initiation of therapy and at the time of the peak serum potassium level. The increase in the serum potassium level was statistically significant ( < 0.0001).

Grahic Jump Location
Grahic Jump Location
Figure 2.
Serial changes in serum potassium concentrations.dotted lines

Values were obtained in five patients during therapy with trimethoprim-sulfamethoxazole (solid lines) and after discontinuation of therapy ( ). Therapy began on day 0.

Grahic Jump Location




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