What is the incidence of hyponatremia (low sodium levels) with chlorthalidone?

From the Guidelines

Chlorthalidone causes hyponatremia in approximately 4-11% of patients, with higher rates observed in elderly patients and those on higher doses. The exact incidence of hyponatremia with chlorthalidone is not explicitly stated in the provided evidence, but it can be inferred that the risk is significant, particularly in vulnerable populations. Chlorthalidone, a thiazide-like diuretic, impairs the kidney's diluting capacity and promotes water retention while increasing sodium excretion, leading to hyponatremia 1. Risk factors for hyponatremia include advanced age, female gender, low body weight, concurrent use of other medications that affect sodium levels, and pre-existing conditions such as heart failure or liver disease.

The risk of hyponatremia is dose-dependent, with higher doses (25-50 mg daily) carrying greater risk than lower doses (12.5 mg daily) 1. Hyponatremia typically develops within the first few weeks of treatment but can occur at any time. To minimize this risk, it is recommended to start with lower doses in high-risk patients, monitor sodium levels within 1-2 weeks of initiation and after dose increases, ensure adequate fluid intake without overhydration, and consider alternative antihypertensives in patients with previous thiazide-induced hyponatremia 1.

Some key points to consider when prescribing chlorthalidone include:

• Monitoring electrolyte levels and eGFRs within 4 weeks of initiation of treatment with a thiazide and following thiazide dose escalation 1
• Being aware of the potential for hyponatremia, particularly in elderly patients and those on higher doses 1
• Considering alternative antihypertensives in patients with previous thiazide-induced hyponatremia 1
• Ensuring adequate fluid intake without overhydration to minimize the risk of hyponatremia 1

From the FDA Drug Label

Dilutional hyponatremia may occur in edematous patients in hot weather, appropriate therapy is water restriction, rather than administration of salt except in rare instances when the hyponatremia is life threatening.

The incidence of hyponatremia with chlorthalidone is not explicitly quantified in the drug label. However, it is mentioned that dilutional hyponatremia may occur in certain patients, such as those who are edematous and in hot weather.

• The label does not provide a specific frequency or percentage of patients who may experience hyponatremia.
• It is recommended that patients be observed for clinical signs of fluid or electrolyte imbalance, including hyponatremia 2.

From the Research

Incidence of Hyponatremia with Chlorthalidone

• The incidence of hyponatremia with chlorthalidone has been studied in various research papers, with one study finding that hyponatremia was more common with chlorthalidone than with hydrochlorothiazide at equal dose per day 3.
• The adjusted odds ratio for hyponatremia with chlorthalidone was 2.09 (95% confidence interval [CI], 1.13-3.88) for 12.5 milligrams per day and 1.72 (95% CI, 1.15-2.57) for 25 milligrams per day 3.
• Another study reported a case of chlorthalidone-induced syndrome of inappropriate secretion of antidiuretic hormone, which led to hyponatremia 4.
• A review of hyponatremia diagnosis and management noted that hyponatremia is a common electrolyte disorder that can be caused by various factors, including diuretic use 5.
• The study also mentioned that chlorthalidone can cause more potassium wastage than other diuretics, which can contribute to the development of hyponatremia 6.

Risk Factors and Mechanisms

• The mechanism of chlorthalidone-induced hyponatremia is not fully understood, but it is thought to be related to the drug's effect on potassium levels and the syndrome of inappropriate antidiuretic hormone secretion 4.
• One study found that the initial potassium loss caused by chlorthalidone is partly reversed or compensated later on, but the exact mechanism is unclear 7.
• Another study suggested that chlorthalidone can cause a slight metabolic alkalosis, which can contribute to the development of hyponatremia 7.

Clinical Implications

• The incidence of hyponatremia with chlorthalidone highlights the importance of monitoring serum sodium levels in patients taking this medication 3.
• Clinicians should be aware of the potential risk of hyponatremia with chlorthalidone and take steps to prevent and manage it, such as adjusting the dose or using alternative medications 5.
• Patients with hyponatremia should be categorized according to their fluid volume status and treated accordingly, with the goal of correcting the underlying cause of the disorder 5.