What are alternative medications to indapamide (thiazide-like diuretic) for patients who cannot tolerate it?

Alternatives to Indapamide for Patients Who Cannot Tolerate It

For patients who cannot tolerate indapamide, chlorthalidone is the preferred alternative thiazide-like diuretic, with calcium channel blockers, ACE inhibitors, or ARBs as appropriate non-diuretic alternatives depending on patient characteristics. 1

First-Line Alternatives to Indapamide

Preferred Thiazide-Like Diuretic Alternative

• Chlorthalidone (12.5-25.0 mg once daily) 1
  • Most evidence-based thiazide-like diuretic with proven cardiovascular outcome benefits
  • Longer duration of action (24-72 hours) compared to conventional thiazides
  • Maintains efficacy down to eGFR of 30 mL/min/1.73 m² 1

Non-Diuretic Alternatives (Based on Patient Characteristics)

1. For patients ≥55 years or Black patients of any age:

   • Calcium channel blocker (CCB) as first alternative 1
   • Examples: amlodipine, nifedipine XL

2. For patients <55 years:

   • ACE inhibitor (e.g., lisinopril, ramipril) 1
   • If ACE inhibitor causes cough or angioedema:
     • ARB (e.g., losartan, valsartan) 1

3. For patients with heart failure:

   • Consider spironolactone (mineralocorticoid receptor antagonist) 1
   • Particularly beneficial in resistant hypertension 1

Alternative Conventional Thiazide Diuretics

• Hydrochlorothiazide (25 mg once or twice daily) 1, 2

  • Less potent than chlorthalidone or indapamide 2
  • Shorter duration of action (6-12 hours)
  • Consider only if patient is stable and well-controlled on it already 1

• Hydrochlorothiazide combined with potassium-sparing diuretics:

  • With amiloride or triamterene 2
  • Helps mitigate potassium loss

Algorithm for Selecting an Alternative

1. First, determine why indapamide is not tolerated:

   • Electrolyte disturbances (hypokalemia)
   • Metabolic effects (hyperglycemia, hyperlipidemia)
   • Other side effects (headache, dizziness)

2. If another diuretic is needed:

   • Try chlorthalidone as the preferred alternative 1
   • If not tolerated, consider conventional thiazides with potassium-sparing agents

3. If diuretics as a class are problematic:

   • Select based on age and race:
     • Age ≥55 or Black patients: CCB
     • Age <55: ACE inhibitor or ARB

4. For resistant hypertension after diuretic intolerance:

   • Follow the step-wise approach 1:
     • Ensure optimal dosing of remaining medications
     • Add spironolactone if potassium allows
     • Consider beta-blockers, alpha-blockers, or central alpha-agonists

Special Considerations

• Renal function: Thiazide-like diuretics maintain efficacy down to eGFR of 30 mL/min/1.73 m²; below this threshold, loop diuretics are preferred 1

• Electrolyte monitoring: Regular monitoring of potassium and sodium is essential when switching between diuretics 3

• Diabetes risk: All thiazide and thiazide-like diuretics can affect glucose metabolism, but this doesn't reduce their cardiovascular benefit 2

• Combination therapy: If monotherapy is insufficient, combine with ACE inhibitor/ARB or CCB based on patient characteristics 1

Pitfalls to Avoid

• Avoid assuming all diuretics have identical side effect profiles - chlorthalidone and indapamide have different metabolic effects than conventional thiazides 4

• Don't overlook concomitant hypomagnesemia when addressing electrolyte issues, as it often coexists with hypokalemia 3

• Avoid abrupt discontinuation of previous therapy - consider gradual transition when switching between antihypertensive classes

• Remember that beta-blockers are not preferred first-line agents for hypertension unless specific indications exist (e.g., coronary disease) 1