Indapamide

Thiazide-like diuretics

ATC code: C03BA11 (Indapamide)

Mechanism of action

Inhibits sodium reabsorption at the distal convoluted tubule via the sodium-chloride cotransporter. Beyond its diuretic effect, it has direct vasodilatory action – reduces vascular smooth muscle tone. Metabolically more neutral than hydrochlorothiazide: less impact on glucose, cholesterol, and uric acid levels.

Indications

Hypertension

First line

Indapamide is the preferred thiazide-like diuretic per ESC/ESH 2024 and NICE. Dose 1.5 mg (sustained release) or 2.5 mg (immediate release) once daily. Antihypertensive efficacy is comparable to amlodipine and ACE inhibitors. Metabolically preferable to hydrochlorothiazide – less impact on potassium, glucose, and lipids.

Isolated systolic hypertension in the elderly

First line

In elderly patients with isolated systolic hypertension, thiazide-like diuretics are first-line. The HYVET trial showed a 30% stroke reduction and 21% all-cause mortality reduction with indapamide (with possible perindopril addition) in patients over 80. The PROGRESS trial confirmed reduced recurrent stroke risk with indapamide plus perindopril.

Practical notes

Timing and administration

Take in the morning, once daily, with or without food. Evening dosing is undesirable due to the diuretic effect. Full antihypertensive effect develops over 1-2 weeks. Sustained-release form (SR, 1.5 mg) provides a smoother effect and causes less hypokalemia.

Monitoring

Check potassium, sodium, creatinine, and uric acid 2-4 weeks after initiation, then every 6 months. Hypokalemia is the main electrolyte side effect, although less pronounced than with hydrochlorothiazide. If potassium drops below 3.5 mmol/L, add potassium supplements or switch to a combination with a potassium-sparing diuretic. Monitor glucose in prediabetic patients.

Safety

Contraindications

Severe renal impairment (eGFR below 30) – loses efficacy
Severe hepatic impairment, hepatic encephalopathy
Hypokalemia
Hypersensitivity to sulfonamides

Serious adverse effects

Severe hyponatremia (especially in elderly patients in hot weather)
Gout provocation (uric acid elevation)
Glucose intolerance (less common than with hydrochlorothiazide)

Common adverse effects

Hypokalemia (less common than with hydrochlorothiazide)
Hyponatremia
Hyperuricemia
Dizziness, orthostatic hypotension

PregnancyFDA B

FDA category B. However, diuretics in general are not recommended in pregnancy as they may reduce uteroplacental blood flow. Not a drug of choice in pregnancy. Methyldopa, labetalol, and nifedipine are preferred.

Breastfeeding

Limited data on excretion in breast milk. Diuretics may reduce lactation. Not prescribed to breastfeeding mothers unless essential.