What is Indaptimide used for and how is it administered?

Indapamide: Clinical Use and Administration

What is Indapamide?

Indapamide is a thiazide-like diuretic (specifically a non-thiazide sulfonamide) used primarily for treating hypertension and managing fluid retention in heart failure. 1, 2

Primary Clinical Indications

Hypertension Management

• Indapamide is recommended as a first-line antihypertensive agent, particularly when thiazide-like diuretics are indicated. 1
• It reduces blood pressure through both diuretic effects and direct vascular actions, decreasing peripheral vascular resistance. 2, 3
• The drug is effective in patients with varying degrees of renal impairment, maintaining efficacy down to eGFR of 30 mL/min/1.73m². 2, 4

Heart Failure with Fluid Retention

• Used to control sodium and water retention in patients with current or prior symptoms of heart failure. 1, 2
• Particularly valuable when combined with other heart failure medications like ACE inhibitors or ARBs. 1, 2

Resistant Hypertension

• Recommended as a replacement for other diuretics in step 2 treatment of resistant hypertension. 2
• Preferred in three-drug combinations: ACE inhibitor (or ARB) + calcium channel blocker + indapamide. 5

Standard Dosing and Administration

Immediate-Release Formulation

• Initial dose: 2.5 mg once daily in the morning 1, 5, 2
• Maximum dose: 5 mg once daily 1, 2
• Duration of action: approximately 36 hours 1, 2

Modified-Release Formulation

• Alternative dosing: 1.5 mg once daily 5
• This formulation provides comparable efficacy with potentially improved tolerability. 5

Dose-Response Relationship

• At 2.5 mg daily: mean serum potassium decrease of 0.5 mEq/L 4
• At 5 mg daily: mean serum potassium decrease of 0.6 mEq/L 4
• Doses of 2.5 mg and 5 mg produce approximately equal effects on blood pressure and edema. 4

Pharmacokinetic Properties

Absorption and Distribution

• Rapidly absorbed with peak blood concentrations within 2 hours 4, 3
• 70% bioavailability; food and antacids do not reduce absorption 3
• Extensively bound to erythrocytes (whole blood/plasma ratio 6:1 at peak) 4
• 71-79% reversibly bound to plasma proteins 4, 3

Metabolism and Elimination

• Terminal half-life: approximately 14-16 hours in whole blood 4, 3
• Extensively metabolized by the liver; only 7% excreted unchanged in urine 4, 3
• 70% eliminated by kidneys, 23% by gastrointestinal tract 4, 3

Important Clinical Considerations

Electrolyte Monitoring

• Monitor serum potassium, sodium, and renal function at baseline, 1-2 weeks after initiation, at 3 months, then every 6 months. 5, 2
• Hypokalemia is the most common electrolyte abnormality, occurring in a dose-dependent manner. 1, 2, 4
• May increase uric acid levels by approximately 1 mg/100 mL. 1, 2

Combination Therapy Adjustments

• When combining with other antihypertensives, reduce the usual dose of other agents by 50% during initial combination therapy. 5
• Particularly effective when combined with ACE inhibitors or ARBs for cardiovascular protection. 1, 2

Special Populations

Renal Impairment:

• Safe and effective even with impaired renal function 4, 3
• Diuretic effects may decline as renal function decreases, but antihypertensive effects persist 4
• No significant drug accumulation in patients with renal impairment 3

Diabetes:

• Preferred thiazide-like diuretic for patients with diabetes and hypertension 1
• Long-acting agents like indapamide are specifically recommended over hydrochlorothiazide 1

Common Pitfalls to Avoid

• Do not use thiazide-like diuretics if eGFR <30 mL/min, except when prescribed synergistically with loop diuretics. 1
• Avoid combining with other potassium-wasting diuretics without appropriate potassium monitoring or supplementation. 1, 2
• Do not exceed 5 mg daily without specialist consultation, as higher doses increase electrolyte disturbances without additional blood pressure benefit. 1, 4
• Monitor for hyponatremia, particularly in elderly patients and those on concurrent medications affecting sodium balance. 1