What is the recommended dosing for indapamide (thiazide-like diuretic) in treating hypertension?

Indapamide Dosing for Hypertension

For hypertension, start indapamide at 1.25 mg once daily in the morning, and if blood pressure remains uncontrolled after 4 weeks, increase to 2.5 mg once daily (maximum 5 mg daily, though higher doses provide minimal additional benefit with increased risk of hypokalemia). 1

Standard Dosing Regimen

Initial Dose

• Start with 1.25 mg once daily taken in the morning for most patients with hypertension 1
• The modified-release formulation can be dosed at 1.5 mg once daily as an alternative 2
• For immediate-release formulations, 2.5 mg once daily is also an acceptable starting dose 2

Dose Titration

• If blood pressure remains inadequate after 4 weeks at 1.25 mg, increase to 2.5 mg once daily 1
• If still uncontrolled after another 4 weeks at 2.5 mg, may increase to 5 mg once daily, though adding another antihypertensive agent is preferred at this point 1
• Research demonstrates that 1.25 mg is as effective as 2.5 mg in maintaining blood pressure control in 74% of patients, with less potassium depletion 3

Maximum Dose

• 5 mg once daily is the maximum dose, but doses above 2.5 mg provide minimal additional blood pressure reduction while significantly increasing hypokalemia risk 1

Special Clinical Contexts

Heart Failure with Fluid Retention

• Start at 2.5 mg once daily in the morning 2, 1
• If inadequate response after 1 week, increase to 5 mg once daily 1
• Duration of action is approximately 36 hours 2

Combination Therapy

• When combining indapamide with other antihypertensives, reduce the usual dose of other agents by 50% during initial combination therapy 1
• The preferred three-drug combination is ACE inhibitor (or ARB) + calcium channel blocker + indapamide 2
• In resistant hypertension (Step 4), consider increasing the thiazide-like diuretic dose if serum potassium is >4.5 mmol/L 2

Renal Impairment

• Indapamide shows no significant accumulation in patients with renal impairment compared to those with normal renal function 4
• 1.25 mg daily is effective and well-tolerated in diabetic patients with moderate renal insufficiency (creatinine <1.5 mg/dl) 5

Important Clinical Considerations

Timing and Monitoring

• Administer in the morning to minimize nocturia 1
• Blood pressure response typically begins within 1-2 weeks, reaches 65% of maximum effect by 1 month, and peaks at 3-4 months 6
• Monitor serum potassium, sodium, and renal function, particularly with doses above 2.5 mg 2

Common Pitfalls to Avoid

• Do not exceed 5 mg daily: Higher doses do not improve efficacy but substantially increase hypokalemia risk 1
• Avoid dose escalation beyond 2.5 mg without considering combination therapy: Adding a second agent is more effective than maximizing indapamide dose 1
• Mean potassium decrease is -0.2 mEq/L at 1.25 mg versus -0.4 mEq/L at 2.5 mg, making lower doses preferable when effective 3

Pharmacokinetic Properties

• Rapidly absorbed with peak levels at 2.3 hours 4
• Terminal half-life of approximately 16 hours 4
• Extensively metabolized with <7% excreted unchanged in urine 4
• Food and antacids do not reduce bioavailability 4

Efficacy Data

• At 2.5 mg daily, achieves satisfactory blood pressure control in approximately 65-75% of patients with mild to moderate hypertension 6, 7
• No tachyphylaxis observed during long-term treatment 6
• Produces mean diastolic pressure reduction of 15-16 mm Hg in clinical trials 7