Hyponatremia and/or Hyperkalemia in Patients Treated with the Standard Dose of Trimethoprim-sulfamethoxazole

• Published in: Internal Medicine Vol. 42; no. 8; pp. 665 - 669
• Main Authors: MORI, Honami, KURODA, Yutaka, IMAMURA, Shigeki, TOYODA, Akira, YOSHIDA, Izumi, KAWAKAMI, Masanobu, TABEI, Kaoru
• Format: Journal Article
• Language: English
• Published: Tokyo The Japanese Society of Internal Medicine 01.08.2003; Japanese Society of Internal Medicine
• Subjects: Anti-Infective Agents - administration & dosage; Anti-Infective Agents - adverse effects; Biological and medical sciences; Creatinine - blood; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; electrolyte disorders; Female; Humans; Hyperkalemia - chemically induced; Hyponatremia - chemically induced; Male; Medical sciences; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Potassium - blood; renal dysfunction; Retrospective Studies; Sodium - blood; TMP-SMX; Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage; Trimethoprim, Sulfamethoxazole Drug Combination - adverse effects; Kidney disease; Human; electrolyte disorders; Hydroelectrolytic balance disorder; Urinary system disease; Renal function; Hyponatremia; TMP- SMX; Trimethoprim; Pharmacology; renal dysfunction; Inorganic element; Hyperkaliemia; Metabolic disorder; Chemotherapy; Sulfamethoxazole; Treatment; Dysfunction; Secondary effect; Antiinfectious; Pharmacokinetics
• ISSN: 0918-2918; 1349-7235
• DOI: 10.2169/internalmedicine.42.665

Objective High-dose trimethoprim-sulfamethoxazole (TMP-SMX) is known to cause hyperkalemia by blocking amiloride-sensitive sodium (Na) channels in distal nephrons. The purpose of this study was to establish whether the standard dose of TMP-SMX could cause electrolyte disorders. Methods and Patients Serum Na, potassium (K) and creatinine (Cr) levels were examined retrospectively in 53 of 77 patients prescribed TMP-SMX, before and after taking the antibiotic combination. Results Electrolyte disorders (Na <135 mEq/l and/or K>5.0 mEq/l) were found in 14 of the 53 patients (26.4%) during TMP-SMX treatment. The average dose was 145.7±24.9 mg/day. The dose of TMP was significantly larger in patients with electrolyte disorders (267.7±84.2 mg vs. 101.9±9.38 mg, p=0.0024). Electrolyte disorders were also seen in 9.1% and 22.2% of patients given the low dose (TMP <80 mg) or standard dose (TMP 80-120 mg) of TMP-SMX, respectively. Electrolyte disorders were seen in 85.7% of patients with renal dysfunction (Cr >1.2 mg/dl), compared with 17.5% of patients with normal renal function (p=0.0008). Logistic regression analysis showed that the dose of TMP and the presence of renal dysfunction increased the incidence of electrolyte disorders with an odds ratio of 2.35 and 80.29, respectively. Conclusion Electrolyte disorders, particularly hyperkalemia and hyponatremia can be detected in patients given TMP-SMX. These disorders are more frequent in patients given high doses, but can also be detected after low-dose administration. Renal dysfunction accelerates the incidence of electrolyte disorders induced by TMP-SMX. (Internal Medicine 42: 665-669, 2003)