How is Indapamide used to treat hypertension?

Indapamide for Hypertension Treatment

Indapamide is a thiazide-like diuretic that is recommended as a first-line treatment for hypertension, either alone or in combination with other antihypertensive medications, particularly ACE inhibitors or ARBs. 1, 2

Mechanism and Pharmacology

• Indapamide has a dual mechanism of action:
  • Primary diuretic effect on the distal renal tubules
  • Direct vascular effect that reduces peripheral vascular resistance 3, 4
• Pharmacokinetics:
  • Rapidly absorbed with peak blood levels in approximately 2 hours
  • Long half-life of 14-16 hours allowing once-daily dosing
  • Extensively metabolized with only about 7% excreted unchanged in urine 2, 4

Dosing and Administration

• Standard dosing:
  • Initial dose: 1.25-2.5 mg once daily
  • Usual maintenance dose: 2.5 mg once daily
  • Maximum dose: 5 mg daily (higher doses provide minimal additional benefit) 2
• Onset of action:
  • Blood pressure reduction begins within 1-2 weeks
  • Reaches 65% of maximum effect by 1 month
  • Maximum effect achieved after 3-4 months of treatment 3

Place in Hypertension Treatment Algorithm

According to the 2024 ESC guidelines 1:

1. First-line therapy options:

   • ACE inhibitors
   • ARBs
   • Dihydropyridine calcium channel blockers
   • Thiazide/thiazide-like diuretics (including indapamide)

2. Preferred combinations:

   • RAS blocker (ACE inhibitor or ARB) + thiazide-like diuretic (such as indapamide)
   • RAS blocker + calcium channel blocker
   • Single-pill combinations are recommended to improve adherence

3. Treatment approach:

   • For most patients with confirmed hypertension (≥140/90 mmHg), combination therapy is recommended as initial treatment
   • For patients ≥85 years, those with frailty, or those with orthostatic hypotension, monotherapy may be considered initially

Special Considerations

• Advantages of indapamide over traditional thiazides:

  • Longer duration of action
  • Potentially fewer metabolic side effects at standard doses
  • Evidence for cardiovascular event reduction 1

• Combination therapy:

  • Particularly effective when combined with ACE inhibitors or ARBs
  • The perindopril-indapamide combination has shown significant reductions in cardiovascular morbidity and mortality 5

• Monitoring:

  • Serum creatinine/eGFR and potassium levels should be monitored at least annually 1
  • Monitor for potential hypokalemia, though this is less common at standard doses 6

Efficacy

• Controls blood pressure in approximately two-thirds of patients with mild to moderate hypertension at the 2.5 mg daily dose 3
• No tachyphylaxis observed during long-term treatment 3
• Comparable efficacy to hydrochlorothiazide but with potentially fewer metabolic side effects 6

Side Effects and Cautions

• Generally well-tolerated with mild and infrequent side effects
• Potential for electrolyte disturbances (particularly hypokalemia), though less common than with traditional thiazides at equivalent doses
• May increase serum uric acid levels
• Use with caution in pregnancy - not recommended for routine use in otherwise healthy pregnant women 2

Resistant Hypertension

For patients not meeting blood pressure targets on three classes of antihypertensive medications (including a diuretic), consider adding a mineralocorticoid receptor antagonist like spironolactone 1.

Indapamide represents an effective option for hypertension management with the advantages of once-daily dosing, good tolerability, and evidence supporting its role in reducing cardiovascular events when used alone or in combination therapy.