Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose

Clin Nephrol. 1996 Sep;46(3):187-92.


Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide spectrum of antimicrobial activity. As a result of the increasing number of AIDS patients requiring therapy for Pneumocystis carinii pneumonia, high dose trimethoprim-sulfamethoxazole use had dramatically increased. A previously unreported and potentially lethal adverse reaction associated with high dose trimethoprim-sulfamethoxazole therapy, hyperkalemia, subsequently developed. Recognition of this potassium disorder led to investigation and description of the mechanism by which trimethoprim-sulfamethoxazole induced hyperkalemia. Trimethoprim was found to act like the potassium-sparing diuretic amiloride and reduce renal potassium excretion. Subsequent to this work, a handful of cases noted the development of hyperkalemia with standard dose trimethoprim-sulfamethoxazole in elderly patients without evidence of an obvious defect in potassium homeostasis. A prospective surveillance study of patients treated with standard dose trimethoprim-sulfamethoxazole as compared to similar controls treated with other antibiotics confirmed the rise in potassium concentration associated with trimethoprim-sulfamethoxazole therapy. Patients with mild renal insufficiency were the only group at significant risk for more severe hyperkalemia. Hence, trimethoprim-sulfamethoxazole therapy can be complicated by hyperkalemia regardless of the dose employed.

Publication types

  • Review

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy
  • Age Factors
  • Animals
  • Anti-Infective Agents / administration & dosage
  • Anti-Infective Agents / adverse effects*
  • Dose-Response Relationship, Drug
  • Humans
  • Hyperkalemia / chemically induced*
  • Kidney / drug effects
  • Pneumonia, Pneumocystis / drug therapy
  • Potassium / blood
  • Renal Insufficiency / complications
  • Risk Factors
  • Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects*


  • Anti-Infective Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Potassium