What medications can cause hyponatremia?

Medications That Can Cause Hyponatremia

Multiple medication classes can cause hyponatremia, with thiazide diuretics, selective serotonin reuptake inhibitors (SSRIs), and certain antiepileptic drugs being the most common culprits. Understanding these medications is essential for prevention, early recognition, and management of drug-induced hyponatremia.

Common Medication Classes Associated with Hyponatremia

1. Diuretics

• Thiazide diuretics: Most commonly implicated in drug-induced hyponatremia 1

  • Mechanism: Impair urinary dilution, cause renal sodium loss, stimulate ADH release, and possibly increase thirst 2
  • Risk is highest within first 2 weeks of therapy but can occur anytime during treatment
  • Hydrochlorothiazide can upregulate aquaporin-2 in the collecting duct without vasopressin 3

• Loop diuretics: Less commonly cause hyponatremia compared to thiazides but still pose a risk 4

  • When combined with thiazides, significantly increase risk of hypovolemia and hyponatremia 4

2. Psychiatric Medications

• SSRIs (fluoxetine, sertraline):

  • Mechanism: Cause syndrome of inappropriate antidiuretic hormone secretion (SIADH) 5, 6
  • FDA label for fluoxetine (Prozac) specifically warns about hyponatremia risk 5
  • Cases with serum sodium lower than 110 mmol/L have been reported 5
  • Sertraline can upregulate vasopressin V2 receptor mRNA and increase cAMP production 3

• Antipsychotics:

  • Mechanism: May induce hyponatremia through nephrogenic syndrome of inappropriate antidiuresis (NSIAD) 3
  • Haloperidol has been shown to upregulate V2R mRNA 3

3. Antiepileptic Drugs

• Carbamazepine:
  • Mechanism: Can cause SIADH 7
  • Risk appears to be dose-related 7
  • FDA label specifically warns about hyponatremia risk 7
  • Upregulates V2R mRNA and increases cAMP production in the absence of vasopressin 3

4. Other Medications

• Oxytocin: Acts as a V2R agonist and can produce hyponatremia when used to induce labor 3
• Desmopressin: Direct V2R agonist used for diabetes insipidus but can cause hyponatremia 3
• Anticancer agents:
  • Vincristine and ifosfamide associated with SIADH 3
  • Cyclophosphamide can upregulate V2R mRNA 3
• NSAIDs: Can attenuate effect of diuretics and potentially contribute to hyponatremia 4

Risk Factors for Drug-Induced Hyponatremia

1. Age: Elderly patients are at significantly higher risk 6, 1
2. Sex: Women are more susceptible than men 1
3. Body mass: Lower body mass increases risk 1
4. Polypharmacy: Combination of multiple medications that affect water excretion 8
   • Particularly dangerous: combined use of thiazide diuretics and SSRIs 8
5. Volume status: Patients with heart failure, cirrhosis, or renal disease 9
6. Fluid intake: Excessive water intake in vulnerable patients 2

Clinical Presentation and Monitoring

• Symptoms correlate with severity and onset rate:

  • Mild (130-134 mmol/L): Often asymptomatic
  • Moderate (125-129 mmol/L): Headache, nausea, confusion
  • Severe (<125 mmol/L): Seizures, altered mental status 10

• Monitoring recommendations:

  • Check electrolytes within 1-2 weeks after starting thiazide diuretics 4
  • Monitor sodium levels in high-risk patients (elderly, women, low body mass) 1
  • For patients on combined thiazides and SSRIs, more frequent monitoring is warranted 8

Prevention and Management

• For thiazide-induced hyponatremia:

  • Consider stopping thiazide or switching to loop diuretic 4
  • Fluid restriction to less than 1L/day for mild to moderate cases 10
  • Monitor for inadvertent rapid correction which is common with thiazide-induced hyponatremia 2

• For SSRI-induced hyponatremia:

  • Consider discontinuation in symptomatic patients 5
  • Elderly patients require closer monitoring 6

• For carbamazepine-induced hyponatremia:

  • Consider dose reduction or discontinuation in symptomatic patients 7
  • Risk appears to be dose-related 7

Caution in Special Populations

• Elderly: Higher risk for all forms of drug-induced hyponatremia; consider lower initial doses and more frequent monitoring 6
• Heart failure patients: Already at risk for hyponatremia; diuretic use requires careful monitoring 4
• Patients with polydipsia: Particularly vulnerable to thiazide-induced hyponatremia 2
• Patients on multiple medications: Check for potential drug interactions that might exacerbate hyponatremia 4

When prescribing medications known to cause hyponatremia, the risk-benefit ratio should be carefully considered, especially in high-risk populations, with appropriate monitoring protocols implemented.