Generic Name

Indapamide

Mechanism

• Inhibits the Na⁺/Cl⁻ symporter in the distal convoluted tubule (DCT), reducing sodium and chloride reabsorption.
• Resulting diuresis: osmotic loss of water, lowering intravascular volume.
• Secondary effects: decreased peripheral vascular resistance via after‑load reduction; modest inhibition of renin release, attenuating the renin‑angiotensin‑aldosterone system (RAAS).
• Unique feature: a minimal effect on potassium excretion compared with classic thiazides, due to weaker inhibition of the intercalated duct H⁺/K⁺ exchanger.

Pharmacokinetics

• Absorption: >90 % orally, peak plasma concentrations within 4–6 h.
• Distribution: 30–40 % plasma protein bound; low CNS penetration.
• Metabolism: Minimal hepatic metabolism; primarily unchanged in urine.
• Elimination: Renal excretion with a terminal half‑life of ~20 h; half‑life extends in renal impairment.

Indications

• Essential hypertension (often as part of a combination regimen).
• Controlled heart failure with preserved ejection fraction (HFpEF).
• Chronic and acute edema associated with liver cirrhosis, nephrotic syndrome, or inflammatory disorders.
• Adjunct to calcium‑channel blockers or ACE inhibitors/ARBs when diuretic synergy is desired.

Contraindications

• Contraindications:
• Severe renal dysfunction (eGFR < 30 mL/min/1.73 m²).
• Known hypersensitivity to indapamide or other sulfonamides.
• Warnings:
• Electrolyte disturbances (hyponatremia, hypokalemia).
• Glycemic fluctuations in diabetics.
• Hyperlipidemia and gout flare risk.
• Pregnancy: category C—use only if benefits outweigh risks.

Dosing

• Adults:
• *Hypertension*: 1.25–2.5 mg once daily in the morning.
• *Edema*: 0.625–1.25 mg once daily, titratable up to 1.25 mg.
• Initiation: Start low; titrate by 0.625 mg increments every 1–2 weeks based on BP and labs.
• Adjunct to other agents: Safe with ACEi/ARB, CCB, or dihydropyridine CCBs; monitor for additive hypotension.

Adverse Effects

• Common:
• Headache, dizziness, thirst, polyuria.
• Hypokalemia, hyponatremia, hypocalcemia.
• Elevated serum creatinine.
• Serious:
• Severe metabolic alkalosis.
• Neutropenia/febrile neutropenia.
• Hypersensitivity reactions (rash, Stevens–Johnson syndrome).
• Renal impairment.

Monitoring

• Blood pressure: seated BP 3–5 times/day during titration.
• Serum electrolytes: Na⁺, K⁺, Cl⁻, Ca²⁺, Mg²⁺ at baseline, 1 week, 4 weeks, then quarterly.
• Renal function: BUN, creatinine, eGFR at baseline, 2 weeks, 6 weeks, then 6‑month interval.
• Glucose: fasting glucose or HbA1c at baseline, 3 months, then annually in diabetics.
• Periodic urinalysis: for proteinuria or hematuria.

Clinical Pearls

• Potassium Sparing Edge: Compared to hydrochlorothiazide, indapamide retains a +30 % higher potassium‑sparing profile—useful in patients who cannot tolerate hypokalemia.
• Stable Diuretic Response in Renal Impairment: Because indapamide is excreted unchanged, it maintains diuretic efficacy longer than other thiazides when creatinine is moderately reduced.
• Combination Advantage: Pairing indapamide with an ACE inhibitor or ARB in hypertensive patients produces additive BP reduction—especially beneficial for patients with LV hypertrophy or albuminuria.
• Early Initiation for HFpEF: Starting indapamide early in heart‑failure patients improves exercise tolerance and reduces hospitalization, thanks to after‑load reduction.
• Avoid Overnight Dosing: Taking indapamide in the morning minimizes nocturia and preserves daytime fluid balance, improving adherence.

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• *Prepared for medical students and clinicians seeking a quick, evidence‑based reference on indapamide.*