Can Indapamide cause hypokalemia?

Indapamide and Hypokalemia: A Significant Risk

Yes, indapamide can cause hypokalemia, and this is a well-documented adverse effect that requires monitoring, especially in elderly patients and women. 1 Indapamide, as a thiazide-like diuretic, carries a significant risk of electrolyte disturbances, with hypokalemia being one of the most common and potentially dangerous complications.

Mechanism and Risk Factors

Indapamide causes hypokalemia through its mechanism of action in the distal convoluted tubule, where it inhibits sodium and chloride reabsorption, leading to increased potassium excretion. The risk factors for developing indapamide-induced hypokalemia include:

• Female sex: Women have a 1.75 times higher risk of developing severe hypokalemia requiring hospitalization 2
• Immediate-release formulation: Associated with 1.41 times higher risk compared to sustained-release formulation 2
• Initial weeks of therapy: 53% of hospitalizations for hypokalemia occur within the first year, with half of those happening in the first 16 weeks 2
• Anorexia or poor oral intake: Can exacerbate existing hypokalemia 3

Clinical Significance and Complications

Hypokalemia caused by indapamide can lead to serious complications:

• Cardiac arrhythmias: Including ventricular flutter, ventricular fibrillation, and torsades de pointes 3, 4
• QT interval prolongation: Observed in patients with indapamide-induced hypokalemia 4, 5
• Neurological symptoms: Including delirium and unsteady gait 5

Incidence and Severity

The FDA label warns that hypokalemia occurs commonly with indapamide, similar to other diuretics 1. In a large population-based study with 147,319 person-years of follow-up, severe hypokalemia requiring hospitalization occurred in 0.8% of patients taking indapamide 2. However, less severe cases of hypokalemia are likely more common.

Monitoring and Prevention

To prevent complications from indapamide-induced hypokalemia:

1. Start with the lowest effective dose: The FDA recommends starting with 1.25 mg rather than higher doses 1
2. Monitor electrolytes regularly: Particularly in the first few months of therapy
3. Use sustained-release formulation when possible to reduce risk 2
4. Exercise caution in high-risk patients: Particularly those on cardiac glycosides, with cardiac arrhythmias, or with poor oral intake 1

Other Electrolyte Disturbances

Indapamide can also cause:

• Hyponatremia: Often occurs concurrently with hypokalemia, especially in elderly females 1, 5
• Hypomagnesemia: Frequently accompanies hypokalemia 5

Clinical Approach

For patients on indapamide:

1. Monitor serum potassium: Especially during the first few months of therapy
2. Consider ECG monitoring: Particularly in patients with cardiac disease 4
3. Be vigilant for neurological symptoms: New-onset delirium or unsteady gait may indicate electrolyte disturbances 5
4. Consider potassium supplementation: In patients at high risk for hypokalemia

Comparison to Other Diuretics

While all thiazide and thiazide-like diuretics can cause hypokalemia, there are differences in potency and risk:

• Chlorthalidone has a higher risk of hypokalemia compared to hydrochlorothiazide 6
• Indapamide's risk profile appears similar to other thiazide-like diuretics, but may be mitigated by using the sustained-release formulation 2

Conclusion

Indapamide therapy carries a significant risk of hypokalemia that can lead to serious cardiac complications. Careful monitoring of serum potassium levels, especially in the early months of therapy and in high-risk populations, is essential to prevent potentially life-threatening complications.