Can Hydrochlorothiazide (HCTZ) cause hypokalemia?

From the Guidelines

Hydrochlorothiazide (HCTZ) can cause hypokalemia, a condition characterized by low potassium levels in the blood, as evidenced by its classification as a thiazide diuretic with known side effects including hypokalemia and hypomagnesaemia 1.

Mechanism of Action

HCTZ works by increasing the amount of salt and water the kidneys remove from the blood, which is then passed in urine. As HCTZ increases urine output, it also increases the excretion of potassium from the body, leading to potential hypokalemia, especially at higher doses or with long-term use.

Clinical Implications

Symptoms of low potassium may include muscle weakness, cramps, fatigue, constipation, and in severe cases, abnormal heart rhythms. To prevent this side effect, doctors often recommend potassium-rich foods (like bananas, oranges, and potatoes), potassium supplements, or sometimes prescribe potassium-sparing diuretics alongside HCTZ.

Monitoring and Prevention

Regular blood tests to monitor potassium levels are important for patients taking HCTZ, particularly when starting the medication or adjusting the dose, as suggested by guidelines for managing high blood pressure 1.

Key Considerations

• Dose and Duration: Higher doses and longer durations of HCTZ use increase the risk of hypokalemia.
• Combination Therapy: Using HCTZ with other medications, such as ACE inhibitors, may require careful monitoring of potassium levels due to potential interactions.
• Patient Education: Patients should be educated on the importance of dietary potassium intake and the recognition of hypokalemia symptoms.

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. Hypokalemia may develop, especially with brisk diuresis when severe cirrhosis is present, during concomitant use of corticosteroid or adrenocorticotropic hormone (ACTH) or after prolonged therapy. Hypokalemia and hypomagnesemia can provoke ventricular arrhythmias or sensitize or exaggerate the response of the heart to the toxic effects of digitalis. Hypokalemia may be avoided or treated by potassium supplementation or increased intake of potassium rich foods

Yes, Hydrochlorothiazide (HCTZ) can cause hypokalemia, especially with high doses, brisk diuresis, severe cirrhosis, concomitant use of corticosteroids or ACTH, or after prolonged therapy 2, 2, 2.

• Key factors that increase the risk of hypokalemia include:
  • High doses of HCTZ
  • Brisk diuresis
  • Severe cirrhosis
  • Concomitant use of corticosteroids or ACTH
  • Prolonged therapy
• Prevention and treatment of hypokalemia may involve potassium supplementation or increased intake of potassium-rich foods.

From the Research

Hydrochlorothiazide (HCTZ) and Hypokalemia

• HCTZ is a thiazide diuretic used to manage hypertension and heart failure, but it can cause mild hypokalemia, metabolic abnormalities, and volume depletion 3.
• Studies have shown that HCTZ can lead to hypokalemia, with a frequency of 12.6% among HCTZ users, equivalent to ~2.0 million US adults 4.
• The risk of hypokalemia is higher in women, non-Hispanic blacks, underweight individuals, and those taking HCTZ for five years or more 4.
• HCTZ has been shown to cause a significant decrease in serum potassium levels, particularly at higher doses 5.
• The occurrence of premature ventricular contractions (PVCs) has been correlated with the fall in serum potassium levels caused by HCTZ therapy 6.

Factors Associated with Hypokalemia

• Demographics: women, non-Hispanic blacks, and underweight individuals are at a higher risk of hypokalemia 4.
• Prescription patterns: monotherapy is associated with a higher risk of hypokalemia compared to fixed-dose combination therapy 4.
• Duration of therapy: participants taking HCTZ for five years or more have a higher risk of hypokalemia 4.
• Potassium supplementation: even among participants taking potassium supplements, hypokalemia was found in 27.2% of those on monotherapy and 17.9% on polytherapy 4.

Comparison with Other Diuretics

• A study comparing HCTZ with chlorthalidone found that chlorthalidone produced a greater incidence and degree of hypokalemia 7.
• HCTZ has been shown to cause greater renal injury than a low potassium diet for the same degree of hypokalemia, suggesting that factors such as chronic ischemia and hyperaldosteronism may be responsible 3.