What medications can cause hyponatremia?

Medications That Cause Hyponatremia

Thiazide diuretics and selective serotonin reuptake inhibitors (SSRIs) are the most common medications implicated in drug-induced hyponatremia, particularly in elderly patients and those with baseline sodium levels at the lower limit of normal. 1

Common Medication Classes Associated with Hyponatremia

Diuretics

• Thiazide diuretics: Highest risk among diuretics

  • Examples: Hydrochlorothiazide, metolazone, indapamide 2
  • Mechanism: Impair urinary dilution, cause renal sodium loss, stimulate ADH, and may have dipsogenic effects 3

• Loop diuretics: Lower risk than thiazides but still significant

  • Examples: Furosemide, bumetanide, torasemide 2
  • High doses (250-500mg of furosemide) significantly increase hyponatremia risk 4

• Potassium-sparing diuretics:

  • Examples: Spironolactone, triamterene, amiloride 2
  • Higher doses (50-100mg of spironolactone) independently associated with hyponatremia 4

Psychotropic Medications

• SSRIs: 3.3 times higher risk of hyponatremia compared to other drug classes 1

  • Examples: Fluoxetine (Prozac), citalopram, sertraline
  • Mechanism: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) 5
  • Incidence: 0.5% to 12% in older adults 1

• Antipsychotics: May cause hyponatremia through intrarenal mechanisms 6

  • Example: Haloperidol upregulates V2 receptor mRNA

• Anticonvulsants:

  • Example: Carbamazepine causes hyponatremia via AQP2 upregulation 6

Other Medications

• Vasopressin analogues:

  • Example: Desmopressin, oxytocin 6
  • Mechanism: Direct V2 receptor agonism

• Anticancer agents:

  • Examples: Vincristine, ifosfamide (cause SIADH) 6
  • Cyclophosphamide (causes NSIAD)

• Proton pump inhibitors: Associated with hyponatremia in clinical practice 7

• Antibiotics: Some have been implicated in hyponatremia 7

Risk Factors for Medication-Induced Hyponatremia

• Age: Elderly patients (>65 years) at significantly higher risk 1
• Gender: Female patients more susceptible 1
• Body weight: Low body weight increases risk 1
• Comorbidities: Heart failure, liver cirrhosis, renal dysfunction 1
• Electrolyte abnormalities: Hypokalemia increases risk 1
• Polypharmacy: Combination therapy (e.g., thiazide + SSRI) has synergistic effect 3

Clinical Presentation

Symptoms depend on severity and rate of development:

• Mild: Headache, difficulty concentrating, memory impairment
• Moderate: Confusion, weakness, unsteadiness (may lead to falls)
• Severe: Hallucinations, syncope, seizures, coma, respiratory arrest, death 1

Management Recommendations

1. Prevention:

   • Identify high-risk patients before prescribing at-risk medications
   • Check baseline sodium before starting high-risk medications
   • Monitor sodium levels within 2-4 weeks of initiation in high-risk patients 1

2. Treatment based on severity:

   • Mild asymptomatic hyponatremia:

     • Consider medication discontinuation or dose reduction
     • Fluid restriction (1-1.5 L/day) if sodium <125 mmol/L 2

   • Moderate to severe symptomatic hyponatremia:

     • Discontinue offending medication
     • Implement fluid restriction
     • Correction rate should not exceed 8-9 mmol/L per day to prevent central pontine myelinolysis 1

3. Specific considerations:

   • For diuretic-induced hyponatremia: Consider dose reduction or alternative agents
   • For SSRI-induced hyponatremia: Consider switching to an antidepressant with lower risk
   • For patients requiring continued therapy: Close monitoring and preventive measures

Special Populations

• Cirrhotic patients: Lower doses of medications that can cause hyponatremia should be used 5
• Heart failure patients: Referral to specialist care recommended if serum sodium <135 mmol/L 2
• Patients with history of hyponatremia: Consider alternative medications with lower risk 1

Remember that medication-induced hyponatremia is often reversible when the offending agent is discontinued, but requires careful monitoring during correction to prevent neurological complications.