Can Hydrochlorothiazide (HCTZ) cause hyponatremia?

From the Guidelines

Hydrochlorothiazide (HCTZ) can cause hyponatremia, as evidenced by the need to monitor for hyponatremia and hypokalemia in patients taking thiazide or thiazide-type diuretics, including HCTZ 1.

Key Points to Consider

• HCTZ is a thiazide diuretic that increases sodium and water excretion through the kidneys, which can sometimes lead to excessive sodium loss and hyponatremia.
• The risk of hyponatremia is higher in certain patient populations, such as the elderly, those taking higher doses of HCTZ (typically above 25mg daily), and when combined with other medications that affect sodium balance.
• Symptoms of hyponatremia may include headache, confusion, nausea, muscle cramps, seizures, and in severe cases, coma.
• Patients taking HCTZ should maintain adequate fluid intake, avoid excessive water consumption, have their electrolyte levels monitored periodically, and be aware of early symptoms of hyponatremia.

Mechanism and Prevention

• The mechanism of HCTZ-induced hyponatremia involves the inhibition of sodium reabsorption in the distal convoluted tubule of the kidney, leading to greater sodium excretion than water excretion in some individuals.
• Monitoring for hyponatremia and hypokalemia, as well as uric acid and calcium levels, is recommended for patients taking thiazide or thiazide-type diuretics, including HCTZ 1.
• Healthcare providers should be aware of the potential for HCTZ to cause hyponatremia and take steps to prevent and monitor for this condition in patients taking this medication.

From the FDA Drug Label

The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis.

• Hyponatremia is listed as a sign or symptom caused by electrolyte depletion due to excessive diuresis.
• The FDA drug label for Hydrochlorothiazide (HCTZ) directly states that hyponatremia can occur, specifically in the context of overdosage and excessive diuresis 2.
• Therefore, yes, HCTZ can cause hyponatremia.

From the Research

HCTZ and Hyponatremia

• HCTZ (Hydrochlorothiazide) can cause hyponatremia, as evidenced by several studies 3, 4, 5, 6, 7.
• The mechanism of thiazide-induced hyponatremia is not fully understood, but it is thought to involve a combination of factors, including:
  • Excessive fluid intake 4
  • Cation (sodium and potassium) depletion 3, 6
  • Osmotic inactivation of sodium 3
  • Reduced ability to excrete free water 4, 6, 7
  • Stimulation of vasopressin secretion 7
  • Reduced distal delivery of filtrate, reduced solute load (urea), and direct inhibition of the sodium-chloride cotransporter 6

Risk Factors

• Risk factors for thiazide-associated hyponatremia include:
  • Age, with older adults being more susceptible 5, 6, 7
  • Female sex 6
  • Low body mass 6
  • Genetic susceptibility 6
  • Concurrent use of other medications that impair water excretion 7

Clinical Manifestations

• Hyponatremia can present with nonspecific symptoms, such as generalized weakness 5
• Severe cases can lead to seizures and/or coma, especially in those with acute onset 6
• Many cases are asymptomatic or have mild symptoms 6