What is the recommended dosage and treatment approach for Indapamide (indapamide) in managing hypertension and edema?

Indapamide Dosage and Treatment Approach for Hypertension and Edema

For hypertension management, indapamide should be prescribed at an initial dose of 1.25 mg once daily, which is as effective as 2.5 mg with fewer side effects. 1 For edema, the recommended starting dose is 2.5 mg once daily, which may be increased if needed.

Dosing Recommendations

For Hypertension:

• Initial dose: 1.25 mg once daily 1
• Usual maintenance dose: 1.25-2.5 mg once daily 2, 3
• Maximum dose: 5 mg daily (rarely needed) 3

For Edema:

• Initial dose: 2.5 mg once daily 3, 4
• Usual maintenance dose: 2.5-5 mg once daily 3, 4
• Maximum dose: 5 mg daily 2, 3

Pharmacological Properties

• Indapamide is a thiazide-like diuretic with additional vasodilatory properties 5, 6
• Onset of action: 1-2 hours after oral administration 3, 5
• Half-life: approximately 14-16 hours, allowing for once-daily dosing 3, 5
• Primarily metabolized by the liver (70% renal elimination, 23% fecal) 3, 5
• Only about 7% excreted unchanged in urine 3

Treatment Approach for Hypertension

First-line Use:

• Indapamide is recommended as a first-line treatment option for hypertension, particularly in patients over 55 years of age 2
• Preferred over conventional thiazides like hydrochlorothiazide due to greater efficacy and metabolic neutrality 2
• Initial dose of 1.25 mg daily is as effective as 2.5 mg with fewer electrolyte disturbances 1

Combination Therapy:

• If blood pressure is not controlled with monotherapy, indapamide can be combined with:
  • ACE inhibitors (particularly perindopril) 2
  • Angiotensin receptor blockers (ARBs) 2
  • Calcium channel blockers 2
• Fixed-dose single-pill combinations are preferred when available 2

Special Populations:

• Particularly effective in elderly patients and Black patients of African or Caribbean origin 2
• Can be used in patients with mild to moderate renal impairment 3
• Not recommended in severe renal impairment (eGFR <30 mL/min) 2

Treatment Approach for Edema

• For edema management, start with 2.5 mg once daily 3, 4
• Efficacy is comparable to 100 mg hydrochlorothiazide for edema treatment 4
• Response typically begins within 2 weeks of treatment 4
• May be used for edema associated with heart failure, particularly HF-PEF (heart failure with preserved ejection fraction) 2

Monitoring and Safety

Electrolyte Monitoring:

• Monitor serum potassium, especially during initial therapy 3, 1
• At 2.5 mg daily, mean decrease in serum potassium is approximately 0.4-0.5 mEq/L 3, 1
• At 1.25 mg daily, mean decrease in serum potassium is approximately 0.2 mEq/L 1

Other Parameters to Monitor:

• Serum uric acid (may increase by approximately 1 mg/100 mL) 3
• Blood glucose in diabetic patients 6
• Blood pressure response (typically evident within 1-2 weeks) 6

Advantages Over Traditional Thiazides

• More potent antihypertensive effect at lower doses 6, 7
• Longer duration of action allowing once-daily dosing 5, 6
• Additional vasodilatory properties that may contribute to BP reduction 5, 6
• Fewer metabolic effects on glucose and lipid profiles 6
• Better tolerated with fewer side effects at lower doses 1, 6

Common Side Effects

• Hypokalemia (dose-dependent and less common with 1.25 mg dose) 3, 1
• Increased uric acid levels 3
• Headache, dizziness, fatigue (generally mild) 7
• Generally well-tolerated compared to traditional thiazides 6, 7

Key Clinical Pearls

• The 1.25 mg dose is as effective as 2.5 mg for hypertension with fewer side effects 1
• No tachyphylaxis has been observed during long-term treatment 6
• No withdrawal syndrome occurs when therapy is discontinued 6
• Indapamide has been shown to be effective in secondary prevention of stroke when combined with perindopril 2
• The antihypertensive effect reaches 65% of maximum within 1 month and maximum effect after 3-4 months 6