Indapamide

Mechanism

Pharmacological Group

Thiazide-like diuretic, derived from indoline sulfonamide.

Mechanism of Action

Shows a biphasic profile of action. At low submaximal doses, it exerts a minimal diuretic effect on the TCD on the NCC symporter, but functions preferentially as a direct peripheral arterial vasodilator. This is achieved by reducing transcellular calcium entry into vascular smooth muscle cells by modulating voltage-gated potassium channels and increasing local synthesis of the vasodilatory prostaglandin PGI₂. At higher doses, the diuretic effect typical of NCC blockade predominates.

Pharmacokinetics

Key Pharmacokinetics

• Absorption: Rapid and complete after oral administration.
• Protein binding: 75-80% reversibly bound to plasma albumin and elastically bound to vascular walls.
• Metabolism: Extensively metabolized in the liver at the microsomal level (CYP3A4) to multiple inactive metabolites.
• Excretion: 60-70% eliminated through the urine as metabolites; 20% excreted via bile and fecal route.
• Half-life: 14 to 18 hours.

Indicators and dose

Clinical Indications

• Essential arterial hypertension: First choice, especially effective in the elderly population and hypertensive patients with metabolic comorbidities. It is the basis of the HYVET study (stroke reduction in people over 80 years of age).
• Management of edema in heart failure.

Dosage and Settings

• Immediate Release: 1.25 mg to 2.5 mg orally once daily.
• Extended Release (LP): 1.5 mg once a day on an empty stomach.
• Renal adjustment: Retains its partial antihypertensive efficacy and vascular protective effects even at CrCl up to 30 mL/min. However, below this rate it loses the net diuretic effect.

Security

Contraindications

Severe liver failure (risk of encephalopathy); anuria; severe hypokalemia; hypersensitivity to sulfas.

Adverse Effects (ADR)

• Common: Mild hypokalemia (significantly less pronounced in 1.5 mg extended-release formulations), headache, postural dizziness, skin dryness.
• Safety differential: It has a neutral metabolic profile. It does not significantly alter plasma lipid levels (cholesterol, triglycerides) nor does it significantly interfere with glycemic control, making it attractive for diabetic or dyslipidemic patients.

Interactions

Risk of nephrotoxicity when combined with cyclosporine. Greater cardiac toxicity due to digoxin in the face of potassium falls.

Pregnancy and Breastfeeding

Category B. Avoid use unless strictly necessary. Its safety profile in breastfeeding is not well documented; not recommended.