title: Incidence of Hyponatremia with High-Dose Trimethoprim-Sulfamethoxazole Exposure.
abstract: BACKGROUND
  Trimethoprim-sulfamethoxazole (TMP-SMX) is a commonly prescribed antibiotic used at high doses for treatment of pneumocystis pneumonia and other infections. Trimethoprim is structurally related to the potassium-sparing diuretic amiloride and has been associated with hyperkalemia and hyponatremia through blocking of epithelial sodium channels in the distal nephron. The incidence of hyponatremia in hospitalized patients treated with high-dose TMP-SMX is unknown.
  
  
  METHODS
  We performed a single-center retrospective chart review of all hospitalized patients who received high-dose TMP-SMX (n = 235) from January 2012 to July 2014. Patients with congestive heart failure, cirrhosis, estimated glomerular filtration rate <30 mL/min/1.73 m2, baseline hyponatremia, and those on other medications associated with hyponatremia were excluded. Hyponatremia was defined as a serum sodium level <136 mEq/L.
  
  
  RESULTS
  Analysis was restricted to 76 unique patients who received more than 8 mg/kg/d of TMP for ≥3 days. Mean starting serum sodium at time of TMP-SMX initiation was 138.4 ± 2.1 mEq/L. Fifty-five patients (72.3%) developed hyponatremia while on therapy, of which 43.6% (n = 24) were cases of serum sodium <130 mEq/L. Mean sodium at the time of nadir was 131.6 ± 5.1 mEq/L. Hyponatremia was noted, on average, 5.5 days after initiation of therapy, with more severe hyponatremia development among African American patients. Urine sodium concentrations were available for 40.0% (22/55) of incident hyponatremia cases, with mean urinary sodium of 104.8 ± 55.9 mEq/L. Hyponatremia often resolved within 3 weeks of drug discontinuation.
  
  
  CONCLUSIONS
  There is a high incidence (72.3%) of hyponatremia associated with the use of high-dose TMP-SMX among hospitalized patients. This is an overlooked and potentially reversible cause of hyponatremia.
authors.affiliation: Department of Pharmacy, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY; Division of Abdominal Transplantation, Department of Surgery, Columbia University, New York, NY.
authors.forename: Demetra
authors.initials: D
authors.lastname: Tsapepas
authors.affiliation: Division of Nephrology, Department of Medicine, Columbia University, New York, NY.
authors.forename: Mariana
authors.initials: M
authors.lastname: Chiles
authors.affiliation: Division of Nephrology, Department of Medicine, Columbia University, New York, NY.
authors.forename: Revekka
authors.initials: R
authors.lastname: Babayev
authors.affiliation: Division of Nephrology, Department of Medicine, Columbia University, New York, NY.
authors.forename: Maya K
authors.initials: MK
authors.lastname: Rao
authors.affiliation: Department of Medicine, Claxton Hepburn Medical Center, Ogdensburg, NY.
authors.forename: Manasvi
authors.initials: M
authors.lastname: Jaitly
authors.affiliation: Department of Pharmacy, New York-Presbyterian Hospital, Columbia University Medical Center, New York, NY.
authors.forename: David
authors.initials: D
authors.lastname: Salerno
authors.affiliation: Division of Nephrology, Department of Medicine, Columbia University, New York, NY; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY. Electronic address: sm2206@cumc.columbia.edu.
authors.forename: Sumit
authors.initials: S
authors.lastname: Mohan
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced* / Q000453:epidemiology; D015994:Incidence; D007297:Inpatients / Q000706:statistics & numerical data; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy*; D012189:Retrospective Studies; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage* / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
keywords: ENaC; Hyperkalemia; Hyponatremia; Trimethoprim