INDAPAMIDE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Indapamide is a thiazide-like diuretic that inhibits sodium reabsorption in the distal convoluted tubule by blocking the Na-Cl cotransporter, leading to increased excretion of sodium, chloride, and water. It also reduces peripheral vascular resistance through direct vasodilatory effects.

What the body does with it

Metabolism	Indapamide is extensively metabolized in the liver primarily via CYP3A4, with multiple metabolites identified. Excretion is mainly renal (60%) and fecal (16-23%).
Excretion	Renal excretion (70% unchanged, 23% as glucuronide conjugate); biliary/fecal elimination accounts for <5%.
Half-life	14–18 hours (terminal elimination half-life); prolonged in renal impairment, supporting once-daily dosing.
Protein binding	71–79% bound to plasma proteins (primarily albumin).
Volume of Distribution	60–100 L (approximately 0.9–1.5 L/kg); indicates extensive extravascular distribution.
Bioavailability	Oral: 93–100%.
Onset of Action	Oral: 1–2 hours; diuretic and antihypertensive effects begin within 2 hours.
Duration of Action	Diuresis lasts up to 24 hours; antihypertensive effect persists for 24 hours with once-daily dosing.

Classification & Brands

Dosing & administration

1.25-2.5 mg orally once daily; 2.5 mg is usual maintenance dose; maximum 5 mg/day.

Dosage form	TABLET
Renal impairment	Contraindicated if eGFR <15 mL/min; use with caution if eGFR 15-30 mL/min; no adjustment needed if eGFR >30 mL/min.
Liver impairment	Contraindicated in severe hepatic impairment (Child-Pugh class C); use with caution in moderate impairment (Child-Pugh class B) with reduced initial dose; no adjustment needed in mild impairment (Child-Pugh class A).
Pediatric use	Not FDA-approved; limited data in children, not typically recommended.
Geriatric use	Initiate at 1.25 mg once daily; monitor for electrolyte disturbances, hypotension, and renal function; increased risk of hyponatremia and hypokalemia.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Other antihypertensive drugs can have additive effects Lithium levels may be increased Can cause hypokalemia and hyponatremia.

Breastfeeding

Indapamide is excreted in breast milk in small amounts. M/P ratio is unknown. Due to potential for serious adverse reactions in the nursing infant (electrolyte imbalances, hypovolemia), use is not recommended during breastfeeding. Monitor infant for dehydration, weight loss, and electrolyte disturbances if used.

Teratogenic Risk

Indapamide is contraindicated in pregnancy. First trimester: Limited data suggest no major malformations but risk of placental hypoperfusion. Second and third trimesters: Fetal and neonatal jaundice, thrombocytopenia, electrolyte disturbances; may cause fetal or neonatal hypovolemia and hypotension due to reduced placental perfusion. Additional risks: Possible association with fetal growth restriction and preterm delivery.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warnings.

Side Effect Profile

Common Effects	Hypokalemia
Serious Effects

Absolute Contraindications

["Anuria","Hypersensitivity to indapamide or sulfonamide-derived drugs","Severe renal impairment (CrCl <30 mL/min)","Hepatic coma or pre-coma"]

Clinical Precautions

Precautions

["Electrolyte disturbances (hypokalemia, hyponatremia, hypomagnesemia, hypochloremic alkalosis)","Hyperuricemia and gout","Sulfonamide hypersensitivity cross-reactivity","Acute myopia and secondary angle-closure glaucoma","Systemic lupus erythematosus exacerbation","Hepatic impairment risk (may precipitate hepatic coma)","Non-melanoma skin cancer risk with cumulative dose"]

Clinical Tips & Counseling

Drug interactions

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