What is the recommended dosage and treatment approach for hypertension using Indapamide?

Indapamide Dosage and Treatment Approach for Hypertension

The recommended starting dose of indapamide for hypertension is 1.25 mg once daily taken in the morning, which can be increased to 2.5 mg after four weeks if blood pressure response is inadequate, with a maximum dose of 5 mg daily if needed. 1

Dosage Recommendations

Initial Treatment

• Starting dose: 1.25 mg once daily in the morning 1
• If response is inadequate after 4 weeks: Increase to 2.5 mg once daily 1
• If response remains inadequate after another 4 weeks: Consider increasing to 5 mg once daily OR adding another antihypertensive agent 1

Clinical Evidence Supporting Lower Dosing

• The 1.25 mg dose has been shown to be as effective as 2.5 mg for blood pressure control in patients with mild to moderate hypertension 2
• Lower doses (1.25 mg) are associated with fewer electrolyte disturbances, particularly less potassium depletion compared to higher doses 2

Place in Hypertension Treatment Algorithm

First-Line Treatment Options

• Indapamide is classified as a thiazide-like diuretic and is recommended as one of the first-line agents for hypertension management 3
• According to the 2024 ESC guidelines, first-line treatments include:
  • ACE inhibitors
  • ARBs
  • Dihydropyridine CCBs
  • Thiazide/thiazide-like diuretics (including indapamide) 3

Combination Therapy

• For most patients with confirmed hypertension (BP ≥140/90 mmHg), combination therapy is recommended as initial treatment 3
• Preferred combinations include:
  • RAS blocker (ACE inhibitor or ARB) + dihydropyridine CCB
  • RAS blocker (ACE inhibitor or ARB) + thiazide-like diuretic (such as indapamide) 3, 4
• Fixed-dose single-pill combinations are recommended to improve adherence 3

Step-wise Treatment Approach

1. Step 1: For patients aged over 55 years and Black patients of African/Caribbean origin, a calcium channel blocker is preferred first-line; if not suitable, a thiazide-like diuretic like indapamide should be offered 3

2. Step 2: If BP is not controlled with monotherapy, add either:

   • ACE inhibitor/ARB + CCB, or
   • ACE inhibitor/ARB + thiazide-like diuretic (indapamide) 3

3. Step 3: If BP remains uncontrolled, use a combination of:

   • ACE inhibitor/ARB + CCB + thiazide-like diuretic (indapamide) 3

4. Step 4: For resistant hypertension, consider adding spironolactone 3

Special Considerations

Specific Populations

• Elderly patients: Indapamide has shown efficacy in elderly patients aged 65-85 years 4
• Diabetes: Indapamide (particularly when combined with an ACE inhibitor) has demonstrated cardiovascular benefits in patients with diabetes 3, 4
• Renal impairment: Can be used in mild to moderate chronic renal failure, though dose adjustment may be required 4

Formulations

• Immediate-release: Available as 1.25 mg and 2.5 mg tablets 1
• Sustained-release (SR): 1.5 mg SR formulation provides smoother pharmacokinetic profile with fewer side effects while maintaining 24-hour efficacy 5

Monitoring

• Monitor serum potassium, creatinine, and estimated glomerular filtration rate at baseline and at least annually 3
• More frequent monitoring may be needed when initiating therapy or increasing doses

Pharmacological Properties

• Mechanism of action: Dual mechanism - diuretic effect at the distal tubule and direct vascular effect 6, 5
• Pharmacokinetics:
  • Rapid absorption with peak levels in approximately 2.3 hours
  • Terminal half-life of approximately 16 hours
  • Once-daily dosing is sufficient due to long half-life 6

Clinical Efficacy

• Indapamide effectively reduces blood pressure in about two-thirds of patients with mild to moderate hypertension 7
• Onset of action is rapid (within 1-2 weeks) with maximum effect after 3-4 months 7
• No tachyphylaxis has been observed during long-term treatment 7

Common Pitfalls and Caveats

• Doses of 5 mg and larger have not shown additional blood pressure-lowering effects but are associated with greater risk of hypokalemia 1
• Monitor for electrolyte imbalances, particularly hypokalemia
• When combining indapamide with other antihypertensive medications, consider reducing the dose of the other agent by 50% initially 1
• Never combine two RAS blockers (ACE inhibitor and ARB) as this combination is not recommended 3

Indapamide offers an effective option for hypertension management with the advantage of once-daily dosing and minimal metabolic side effects compared to traditional thiazide diuretics.