From the Guidelines
Chlorthalidone commonly causes several electrolyte abnormalities, with hypokalemia (low potassium) being the most significant concern, and also frequently causes hyponatremia (low sodium), hypochloremia (low chloride), hypercalcemia (high calcium), and hypomagnesemia (low magnesium) as reported in the 2021 study 1. These electrolyte disturbances occur because chlorthalidone works by inhibiting sodium and chloride reabsorption in the distal convoluted tubule of the kidney, which increases urinary excretion of these electrolytes along with water. The resulting increased potassium secretion leads to hypokalemia, which may require potassium supplementation or potassium-sparing diuretics in some patients. Hypomagnesemia often accompanies hypokalemia and can make potassium replacement less effective if not corrected. The hypercalcemic effect differs from loop diuretics, which cause hypocalcemia. Some key points to consider when using chlorthalidone include:
- Monitoring electrolyte levels, especially potassium, within 4 weeks of initiation of treatment and after dose escalation, as recommended by the 2019 KDOQI US commentary on the 2017 ACC/AHA hypertension guideline 1.
- Being aware of the potential for hyponatremia, particularly in the elderly, as noted in the same commentary.
- Considering the use of chlorthalidone in patients with advanced CKD, as it may be effective for BP management and is associated with lower risk of incident HF, as discussed in the 2019 KDOQI US commentary 1. Patients on chlorthalidone should have their electrolytes monitored regularly, especially during the initial weeks of therapy and after dose adjustments, with particular attention to potassium levels to prevent cardiac arrhythmias and other complications of electrolyte imbalances, as supported by the evidence from the 2018 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.
From the FDA Drug Label
PRECAUTIONS General Hypokalemia may develop with chlorthalidone as with any other diuretic, especially with brisk diuresis when severe cirrhosis is present or during concomitant use of corticosteroids or ACTH. Any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease) Dilutional hyponatremia may occur in edematous patients in hot weather, Thiazide-like diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia. Calcium excretion is decreased by thiazide-like drugs Pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been observed in few patients on thiazide therapy.
The electrolyte abnormalities caused by Chlorthalidone (Thiazide-like Diuretic) are:
- Hypokalemia (low potassium levels)
- Hypochloremia (low chloride levels)
- Hypomagnesemia (low magnesium levels)
- Dilutional hyponatremia (low sodium levels)
- Hypercalcemia (high calcium levels)
- Hypophosphatemia (low phosphate levels) 2
From the Research
Electrolyte Abnormalities Caused by Chlorthalidone
- Hypokalemia: Chlorthalidone can cause hypokalemia, as seen in a case report of a 52-year-old male who developed severe hypokalemia and rhabdomyolysis after increasing his chlorthalidone dose from 25 mg to 50 mg daily 3.
- Hyponatremia: Chlorthalidone is associated with a higher risk of hyponatremia compared to hydrochlorothiazide, with an adjusted odds ratio of 2.09 (95% CI, 1.13-3.88) for 12.5 mg per day and 1.72 (95% CI, 1.15-2.57) for 25 mg per day 4.
- Potassium deficiency: Chlorthalidone can cause potassium deficiency, with a mean potassium deficit of 176 mmol on day 9 in patients receiving a normal-sodium diet and 276 mmol on day 13 in patients receiving a low-sodium diet 5.
- Electrolyte imbalances: Chlorthalidone is associated with a higher risk of electrolyte abnormalities, including hypokalemia, hyponatremia, and acute renal failure, compared to hydrochlorothiazide 6.
Factors Influencing Electrolyte Abnormalities
- Dietary sodium restriction: Dietary sodium restriction can increase diuretic-induced potassium loss, presumably by an increased activity of the renin-angiotensin-aldosterone system 5.
- Dose and duration of treatment: The risk of electrolyte abnormalities may increase with higher doses and longer duration of chlorthalidone treatment 3, 6.
- Comparison with other diuretics: Chlorthalidone may have a higher risk of electrolyte abnormalities compared to other diuretics, such as hydrochlorothiazide 6, 4.