eISSN: 2373-6372 GHOA

Gastroenterology & Hepatology: Open Access
Volume 4 Issue 2 - 2016
Hyponatremic Seizure Associated with Concomitant Use of Standard Dose Trimethoprim-Sulfamethoxazole with a Diuretic
Lynda Hoang*, Rabaiya Ali, Jose Manriquez and Sulaiman Sultan
Internal Medicine Residency, Parkview Medical Center, USA
Received: January 26, 2016 | Published: February 12, 2016
*Corresponding author: Lynda Hoang, Internal Medicine Residency, Parkview Medical Center, USA, Email:
Citation: Hoang L, Ali R, Manriquez J, Sultan S (2016) Hyponatremic Seizure Associated with Concomitant Use of Standard Dose Trimethoprim-Sulfamethoxazole with a Diuretic. Gastroenterol Hepatol Open Access 4(2): 00095. DOI:10.15406/ghoa.2016.04.00095


Trimethoprim-Sulfamethoxazole (TMP-SMX) is an antimicrobial agent used to treat infectious disease pathogens [1]. Electrolyte abnormalities, primarily hyperkalemia and hyponatremia, are rare adverse effects reported with higher doses of trimethoprim use [2]. Paucity of data exists for similar effects in patients using standard doses of TMP- SMX [3], with no previous reported case of trimethoprim induced hyponatremic seizure in the literature. We illustrate a case of severe hyponatremia and hyponatremic seizure in a patient on regular dose of TMP-SMX who was concomitantly using a diuretic.

A 64-year old hypertensive female taking Lisinopril-HCTZ (20-12.5mg) combination pill was started on TMP-SMX (160-800 mg) twice daily for left fourth toe blister. She presented to the emergency room four days later with fatigue, confusion, and a witnessed grandmal seizure. Physical examination, electrocardiogram, urinalysis, chest X-ray, and cranial computed tomography were unremarkable. Serum Na was measured at 119mmol/L (136-145mmol/L) compared to 131mmol/L last week prior to antibiotic use. Other labs included TSH 0.94U/L, glucose 109 mg/dl , K 3.9 (3.5-5.1mmol/L), SOsm 245mOsmL/kg (280- 303mOsm/Kg), BUN 10mg/dL (7-18mg/dl), SCr 0.9mg/dL (0.4-0.9mg/dL), BUN: SCr 11.1 (10.0-20.0) and creatinine clearance 52.2 mL/min using Cockcroft-Gault equation. Urinary indices showed UOsm 205mOsm/kg (50-800 mOsm/kg), UNa 22mmol/L, UCr 24.5mg/dL and FENa 0.7%. TMP-SMX and Lisinopril-HCTZ were discontinued. The patient received hypertonic saline. Serum Na gradually improved to 131mmol/L over 24 hours and the patient’s confusion resolved without further seizures.

Trimethoprim, a heterocyclic weak base, structurally mimics potassium-sparing diuretics, and at higher doses causes natriuresis by blocking sodium reabsorption in the distal nephron [4]. Hyponatremia, while usually asymptomatic, can exert neurological sequelae. In our case, standard dose TMP-SMX lead to salt wasting and severe hyponatremia which manifested as seizure; its dose- dependent effect was perhaps potentiated by the concomitant use of a diuretic which can induce renal dysfunction and affect sodium and water hemostasis.


  1. Khow KS, Yong TY (2014) Hyponatraemia associated with trimethoprim use. Curr Drug Saf 9(1): 79-82.
  2. Babayev R, Terner S, Chandra S, Radhakrishnan J, Mohan S (2013) Trimethoprim-associated hyponatremia. Am J Kidney Dis 62(6): 1188-1192.
  3. Mori H, Kuroda Y, Imamura S, Toyoda A, Yoshida I, et al. (2003) Hyponatremia and/or hyperkalemia in patients treated with the standard dose of trimethoprim-sulfamethoxazole. Intern Med 42(8): 665-669.
  4. Choi MJ, Fernandez PC, Patnaik A, Coupaye-Gerard B, D'Andrea D, et al. (1993) Brief report: trimethoprim-induced hyperkalemia in a patient with AIDS. N Engl J Med 328(10): 703-706.
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