Does Indapamide cause hypokalemia (low potassium levels)?

Does Indapamide Cause Low Potassium?

Yes, indapamide can cause hypokalemia (low potassium levels), which is a well-documented side effect of this thiazide-like diuretic. 1 The FDA drug label explicitly lists hypokalemia as one of the major adverse effects of indapamide therapy.

Mechanism and Risk

Indapamide, classified as a thiazide-like diuretic, works by increasing sodium and water excretion in the kidneys. This mechanism also leads to increased potassium excretion, which can result in hypokalemia. According to clinical guidelines, this effect is similar to other thiazide and loop diuretics 2.

Risk Factors for Indapamide-Induced Hypokalemia:

• Female sex (1.75 times higher risk) 3
• Immediate-release formulation (versus sustained-release) 3
• Poor nutritional status or anorexia 4
• Higher doses (2.5mg or 5mg versus 1.25mg) 1
• Longer duration of therapy without monitoring

Incidence and Severity

The incidence of hypokalemia with indapamide varies by dosage:

• At 1.25mg daily: 20% of patients had at least one potassium value below 3.4 mEq/L 1
• At 2.5mg daily: 47% of patients had at least one potassium value below 3.5 mEq/L 1
• At 5mg daily: 72% of patients had at least one potassium value below 3.5 mEq/L 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, with 53% of these hospitalizations occurring within the first year of treatment 3.

Clinical Consequences

Hypokalemia from indapamide can range from mild and asymptomatic to severe and life-threatening:

• Mild cases: Often asymptomatic, detected only through laboratory monitoring
• Moderate cases: May cause muscle weakness, fatigue, or cramping
• Severe cases: Can lead to dangerous cardiac arrhythmias including ventricular flutter, ventricular fibrillation, and torsades de pointes 4, 5

Case reports document fatal arrhythmias associated with indapamide-induced hypokalemia, particularly in elderly patients with poor nutritional status 4.

Prevention and Management

To prevent and manage indapamide-induced hypokalemia:

1. Start with the lowest effective dose (1.25mg rather than 2.5mg) 1
2. Monitor serum potassium levels:
   • At baseline before starting therapy
   • 1-2 weeks after initiation
   • After any dose increase
   • Periodically during maintenance therapy (every 3-6 months) 2
3. Consider sustained-release formulations which have a lower risk of hypokalemia 3
4. Be vigilant in high-risk patients:
   • Elderly patients
   • Those with poor nutritional intake
   • Patients with cardiac disease
   • Those taking cardiac glycosides (digoxin) 2
5. Treatment options for hypokalemia:
   • Potassium supplements
   • Addition of potassium-sparing diuretics if persistent hypokalemia occurs 2
   • Consider ACE inhibitors or ARBs as they tend to increase potassium levels 2

Conclusion

Indapamide definitively causes hypokalemia in a significant percentage of patients, with risk increasing at higher doses. While most cases are mild to moderate, severe and potentially life-threatening hypokalemia can occur, particularly in vulnerable populations. Regular monitoring of serum potassium is essential for safe use of this medication.