indapamide
thiazide-like diuretic· Brands: Natrilix, LozolPO
Mechanism of action
Indapamide reduces sodium and water retention by inhibiting the reabsorption of sodium chloride in the distal convoluted tubule. It also has a direct vasodilatory effect on vascular smooth muscle, contributing to its antihypertensive action.
Pharmacokinetics
Indapamide is well absorbed after oral administration with peak plasma concentrations occurring within 1 to 2 hours. It is extensively metabolised in the liver, and has a plasma half-life of about 14 to 18 hours. Excretion is predominantly via the urine, with about 70% of a dose eliminated as metabolites and the remainder as unchanged drug. It distributes into red blood cells and binds to plasma proteins.
Indications & dosing
Hypertension
Modified-release 1.5 mg once daily or immediate-release 2.5 mg once daily. May be used as monotherapy or in combination.
- adult · PO: 1.5–2.5 mg once daily · Modified-release 1.5 mg once daily or immediate-release 2.5 mg once daily. May be used as monotherapy or in combination.
Edema associated with heart failure
Usually 2.5 mg once daily; if response inadequate, may increase to 5 mg once daily.
- adult · PO: 2.5 mg once daily · Usually 2.5 mg once daily; if response inadequate, may increase to 5 mg once daily.
Contraindications & precautions
- Severe renal impairment (anuria) · Indapamide is ineffective in severe renal impairment and may cause drug accumulation.
- Hepatic encephalopathy or severe hepatic impairment · May precipitate encephalopathy due to electrolyte disturbances.
- Hypersensitivity to indapamide or other sulphonamides · Cross-sensitivity may occur.
- Monitor serum electrolytes, especially potassium and sodium, at the start of treatment and periodically, particularly in patients at risk of electrolyte imbalance.
- Caution in patients with gout or diabetes, as indapamide can increase uric acid and blood glucose levels.
- Avoid use in pregnancy and breastfeeding.
- Caution in patients with mild to moderate hepatic impairment, with dose adjustment or close monitoring.
Adverse effects
- Hypokalaemiaserious
- Hyponatraemiaserious
- Hyperuricaemia
- Dizziness
- Gastrointestinal disturbances (nausea, constipation)
- Pancreatitisserious
Renal & hepatic adjustment
- eGFR 0–29: Avoid in severe renal impairment (eGFR < 30 ml/min). Ineffective and risk of accumulation. (avoid)
- Hepatic impairment (mild): No adjustment required.
- Hepatic impairment (moderate): Use with caution; monitor electrolytes, renal and liver function.
- Hepatic impairment (severe): Avoid in severe hepatic impairment due to risk of hepatic encephalopathy. (avoid)
Monitoring, pregnancy & toxicity
- Blood pressure · Regularly
- Serum electrolytes (Na+, K+) · Before starting and periodically
- Renal function (creatinine, eGFR) · At baseline and periodically
- Blood glucose · Periodically, especially in diabetic patients
- Uric acid · Periodically
- Pregnancy: Indapamide is not recommended during pregnancy. Use only if clearly indicated and alternative treatments are unsuitable. It may reduce placental perfusion and affect fetal growth. If used, monitor fetal growth and maternal blood pressure.
- Toxicity: Electrolyte disturbances, particularly hypokalemia and hyponatremia · Monitor serum electrolytes; replace potassium and sodium as needed.
- Toxicity: Hypotension and dehydration · Supportive care; administer IV fluids to restore circulating volume.
- Toxicity: Nausea, vomiting, and dizziness · Stop the drug and provide symptomatic treatment.
- Toxicity: In severe overdose, arrhythmias may occur · Continuous ECG monitoring; treat life-threatening arrhythmias per ACLS protocols.
Clinical notes
Indapamide is used for the treatment of essential hypertension and for oedema associated with heart failure. It can be given once daily, usually in the morning. Monitor serum electrolytes, renal function, and blood glucose, particularly in patients at risk of hypokalaemia, gout, or diabetes. Common adverse effects include hypokalaemia, hyperuricaemia, and dizziness. It may potentiate the effects of other antihypertensive agents and is contraindicated in severe renal impairment, hepatic encephalopathy, and hypersensitivity to sulfonamides.
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BNF; local formulary