Is there a thiazide diuretic (thiazide) that is less likely to cause hypokalemia (low potassium levels)?

From the Guidelines

Hydrochlorothiazide is actually a thiazide diuretic that is less likely to cause hypokalemia compared to chlorthalidone, according to the most recent and highest quality study available 1.

Key Points to Consider

• The study found that chlorthalidone has a higher potency than hydrochlorothiazide, which may influence the dosage of the drug provided to meet target goals and lead to differences in adverse effects such as hypokalemia.
• A retrospective cohort of elderly participants reported that chlorthalidone significantly increased the risk for hospitalization due to hypokalemia compared with hydrochlorothiazide.
• The concurrent use of potassium-sparing antihypertensives with thiazides or thiazide-like drugs may modify the risk of hypokalemia in a complex and drug-specific manner.

Recommendations for Clinical Practice

• Hydrochlorothiazide can be considered as a thiazide diuretic option with a lower risk of hypokalemia, especially when compared to chlorthalidone.
• Monitoring of potassium levels is still essential, especially in patients taking other medications that might affect potassium levels, such as ACE inhibitors or potassium supplements.
• Combining hydrochlorothiazide with potassium-sparing diuretics like spironolactone or amiloride can further reduce the risk of hypokalemia if necessary.

Important Considerations

• The choice of thiazide diuretic should be individualized based on patient-specific factors, such as kidney function, comorbidities, and concomitant medications.
• Regular monitoring of electrolyte levels, including potassium, is crucial to minimize the risk of hypokalemia and other adverse effects associated with thiazide diuretics.

From the FDA Drug Label

In published studies, clinically significant hypokalemia has been consistently less common in patients who received 12. 5 mg of hydrochlorothiazide than in patients who received higher doses. The answer to the question of whether there is a thiazide diuretic that is less likely to cause hypokalemia is:

• Low-dose hydrochlorothiazide (12.5 mg) may be less likely to cause hypokalemia compared to higher doses, based on published studies 2.
• However, it is essential to note that hypokalemia can still occur even with low-dose hydrochlorothiazide, especially in certain patient populations or with concomitant use of other medications.
• Periodic monitoring of serum electrolytes is recommended to minimize the risk of hypokalemia.

From the Research

Thiazide Diuretics and Hypokalemia

• Thiazide diuretics are commonly used to treat hypertension, but they can cause hypokalemia (low potassium levels) as a side effect 3, 4, 5, 6, 7.
• The risk of hypokalemia varies among different thiazide diuretics, with some studies suggesting that chlorthalidone may be more likely to cause hypokalemia than hydrochlorothiazide 6, 7.
• A study published in 2021 found that chlorthalidone use was associated with a higher risk of hypokalemia compared to hydrochlorothiazide use, particularly in patients with higher estimated glomerular filtration rate (eGFR) 6.
• Another study published in 2013 found that patients treated with chlorthalidone were more likely to be hospitalized with hypokalemia or hyponatremia compared to those treated with hydrochlorothiazide 7.
• In contrast, a study published in 2010 found that the incidence of hypokalemia between chlorthalidone and hydrochlorothiazide appeared comparable at equipotent dosages 5.

Comparison of Chlorthalidone and Hydrochlorothiazide

• Several studies have compared the effectiveness and safety of chlorthalidone and hydrochlorothiazide in older adults 6, 7.
• A study published in 2021 found that chlorthalidone use was associated with a higher risk of eGFR decline, cardiovascular events, and hypokalemia compared to hydrochlorothiazide use 6.
• Another study published in 2013 found that chlorthalidone was not associated with fewer adverse cardiovascular events or deaths than hydrochlorothiazide, but was associated with a greater incidence of electrolyte abnormalities, particularly hypokalemia 7.
• The available evidence suggests that hydrochlorothiazide may be a better option than chlorthalidone for patients at risk of hypokalemia 4, 6, 7.