What is important to know about Indapamide (a diuretic)?

Indapamide: Key Clinical Information

Indapamide is a thiazide-like diuretic that is preferred over traditional thiazides for hypertension management due to its superior cardiovascular outcomes and longer duration of action. 1

Mechanism of Action and Pharmacology

• Indapamide is an oral antihypertensive/diuretic with a dual mechanism of action:
  • Diuretic effect at the distal tubule
  • Direct vascular effect that decreases peripheral vascular resistance 2, 3
• Pharmacokinetics:
  • Rapidly absorbed with peak concentrations within 2 hours
  • Long half-life of approximately 14-16 hours allowing once-daily dosing
  • Extensively metabolized with only 7% excreted unchanged in urine
  • 70% eliminated by kidneys and 23% through gastrointestinal tract 2, 4

Dosing and Formulations

• Available in two formulations:
  • Immediate-release: 1.25 mg and 2.5 mg tablets
  • Sustained-release: 1.5 mg tablets
• Recommended starting dose: 1.25 mg once daily for hypertension
• Dose can be increased to 2.5 mg if needed, but higher doses don't provide significantly greater antihypertensive effect 5
• The sustained-release formulation (1.5 mg) provides smoother pharmacokinetics with fewer side effects 3

Clinical Efficacy

• Effectively reduces blood pressure in approximately two-thirds of patients with mild to moderate hypertension 6
• Onset of action is rapid (1-2 weeks) with maximum effect after 3-4 months
• No tachyphylaxis observed during long-term treatment 6
• Particularly effective for reducing systolic blood pressure with 24-hour efficacy 3
• Considered a preferred thiazide-like diuretic along with chlorthalidone in current guidelines 1

Role in Hypertension Management

• Recommended as one of four first-line agents for hypertension management in patients with diabetes 1
• Particularly valuable in combination therapy:
  • Can be combined with ACE inhibitors, ARBs, beta-blockers, and other antihypertensives
  • The combination of perindopril (ACE inhibitor) and indapamide has shown significant cardiovascular benefits 7
• Preferred over hydrochlorothiazide (HCTZ) due to:
  • More effective BP lowering, especially at night
  • Longer half-life
  • Better cardiovascular outcomes data 1

Monitoring and Safety

• Monitor serum creatinine/eGFR and potassium levels at least annually when used with ACE inhibitors, ARBs, or as monotherapy 1
• Electrolyte changes:
  • Can cause hypokalemia, but less frequently than with traditional thiazides
  • At 1.25 mg, mean decrease in serum potassium is approximately 0.2 mEq/L
  • At 2.5 mg, mean decrease is approximately 0.4-0.6 mEq/L 2, 5
• May increase uric acid levels by approximately 0.7-1 mg/dL 2
• Generally well-tolerated with mild and rare side effects 6
• Limited impact on carbohydrate and lipid metabolism compared to traditional thiazides 6

Special Considerations

• Safe for use in patients with mild to moderate renal impairment
• Contraindicated in pregnancy - should be avoided in sexually active individuals of childbearing potential who aren't using reliable contraception 1
• May be particularly beneficial in resistant hypertension when added to existing regimens 1
• Can be used in elderly patients with appropriate monitoring

Clinical Pearls

• When treating hypertension in patients with diabetes, indapamide is one of the preferred thiazide-like diuretics shown to reduce cardiovascular events 1
• For patients with albuminuria (UACR ≥30 mg/g), an ACE inhibitor or ARB should be the first-line agent, but indapamide can be an effective add-on therapy 1
• The lower dose (1.25 mg) is as effective as 2.5 mg for most patients while causing fewer metabolic disturbances 5
• No withdrawal syndrome has been observed when discontinuing therapy 6