From the Guidelines
Chlorthalidone carries a significant risk of hyponatremia, and patients taking this medication should be closely monitored for serum sodium levels, particularly during the first few weeks of treatment and after dose adjustments, as recommended by the 2017 ACC/AHA guideline 1. The risk of hyponatremia associated with chlorthalidone is higher in certain patient populations, including the elderly, those with lower body weight, women, and patients with impaired renal function, as well as those taking other medications that can affect sodium levels 1.
- Typical symptoms of hyponatremia include headache, confusion, nausea, muscle cramps, seizures, and in severe cases, coma.
- To minimize the risk of hyponatremia, it is recommended to start with lower doses of chlorthalidone (12.5mg daily) and ensure adequate fluid intake, but not excessive, as well as maintain reasonable salt intake 1.
- Regular electrolyte monitoring is crucial, especially in high-risk patients, and should be performed within 4 weeks of initiation of treatment with chlorthalidone and after dose escalation, as suggested by the KDOQI US commentary on the 2017 ACC/AHA hypertension guideline 1.
- If hyponatremia develops, treatment may require chlorthalidone dose reduction or discontinuation, fluid restriction, and in severe cases, administration of hypertonic saline under medical supervision. The longer half-life of chlorthalidone (40-60 hours) compared to hydrochlorothiazide (6-15 hours) contributes to its increased risk of electrolyte disturbances, including hyponatremia, and highlights the importance of careful monitoring and management of patients taking this medication 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 risk of hyponatremia (low sodium levels) associated with Chlorthalidone is possible, particularly in edematous patients in hot weather, where dilutional hyponatremia may occur. Key points to consider:
- Hyponatremia can occur due to dilutional effects
- Edematous patients in hot weather are at higher risk
- Water restriction is the recommended therapy, except in life-threatening cases where salt administration may be necessary 2
From the Research
Risk of Hyponatremia with Chlorthalidone
- The risk of hyponatremia associated with chlorthalidone has been investigated in several studies 3, 4, 5, 6, 7.
- A population-based case-control study found that hyponatremia was more common with chlorthalidone than with hydrochlorothiazide at equal dose per day, with an adjusted odds ratio of 2.09 (95% 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 found that chlorthalidone therapy improved blood-pressure control at 12 weeks, but was associated with a higher risk of hypokalemia, reversible increases in serum creatinine level, hyperglycemia, dizziness, and hyperuricemia, as well as hyponatremia 5.
- A pilot study found that chlorthalidone significantly reduced blood pressure in patients with moderate to advanced chronic kidney disease, but was associated with adverse events including hyponatremia, hypokalemia, hyperuricemia, and transient creatinine changes 7.
- The use of chlorthalidone in patients with renal insufficiency requires careful consideration of dosages, titration, and monitoring to prevent hypovolemia, hyponatremia, and hypokalemia 6.
Comparison with Other Diuretics
- Chlorthalidone has been compared to hydrochlorothiazide in terms of the risk of hyponatremia, with chlorthalidone found to have a higher risk at equal dose per day 3.
- Loop diuretics may be necessary in patients with more advanced renal insufficiency, and may have a different risk profile for hyponatremia compared to chlorthalidone 6.