Indapamide

Indapamide is a thiazide-like diuretic used to treat high blood pressure (hypertension). It is available as standard-release tablets (2.5 mg) and modified-release tablets (1.5 mg).

Indapamide works by helping the kidneys remove excess salt and water from the body, which lowers blood pressure.

It has fewer metabolic side effects than traditional thiazide diuretics.

Indapamide is a prescription-only medicine (POM) in the UK and is available as a generic or under the brand name Natrilix.

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Indapamide is a prescription-only medicine used to treat high blood pressure (hypertension).

It belongs to a class of medicines known as thiazide-like diuretics and is available as standard-release tablets (2.5 mg) and modified-release tablets (1.5 mg, sold under the brand name Natrilix SR).

Indapamide works by helping the kidneys remove excess sodium and water from the body, which reduces blood volume and lowers blood pressure.

It also relaxes blood vessel walls directly, providing an additional blood pressure-lowering effect.

Compared with older thiazide diuretics such as bendroflumethiazide, indapamide causes fewer disturbances to blood sugar, cholesterol, and uric acid levels.

Hypertension is one of the leading modifiable risk factors for cardiovascular disease in the United Kingdom.

Data from the British Heart Foundation indicate that approximately one in three adults in the UK has high blood pressure, yet many remain undiagnosed because the condition rarely produces noticeable symptoms until serious organ damage has occurred.

Persistently elevated blood pressure increases the risk of stroke, heart attack, heart failure, chronic kidney disease, peripheral arterial disease, and vascular dementia.

Effective treatment of hypertension reduces these risks substantially.

This page provides a comprehensive clinical overview of indapamide, covering how it works, who should take it, dosage guidance, potential side effects, important safety warnings, and how to obtain a prescription in the United Kingdom.

Important safety information about indapamide

Before reading further, note these essential safety points about indapamide.

  • Indapamide is a prescription-only medicine (POM) and must be used under medical supervision.
  • Regular blood tests are required to monitor sodium, potassium, and kidney function.
  • Low sodium (hyponatraemia) and low potassium (hypokalaemia) are clinically important risks, particularly in older adults.
  • Do not increase the dose above the recommended amount. Higher doses do not lower blood pressure further and increase the risk of side effects.
  • Tell your prescriber about all other medicines you take, including over-the-counter painkillers and herbal products.

Understanding hypertension

Blood pressure is the force that circulating blood exerts against the walls of the arteries.

It is measured in millimetres of mercury (mmHg) and expressed as two numbers: systolic pressure (when the heart contracts and pumps blood out) over diastolic pressure (when the heart relaxes between beats).

NICE guideline NG136 defines hypertension as a clinic blood pressure of 140/90 mmHg or higher, confirmed by ambulatory or home blood pressure monitoring showing an average of 135/85 mmHg or above.

Hypertension is classified into stages. Stage 1 hypertension corresponds to a clinic reading of 140/90 to 159/99 mmHg. Stage 2 corresponds to 160/100 to 179/119 mmHg.

Stage 3, or severe hypertension, is defined as a clinic reading of 180/120 mmHg or above and requires urgent assessment.

Most hypertension is classified as primary (or essential), meaning no single identifiable cause can be found.

Secondary causes, including renal artery stenosis, primary aldosteronism, phaeochromocytoma, and Cushing syndrome, are less common and are typically investigated if hypertension is resistant to treatment or presents at a young age.

The management of hypertension begins with lifestyle modifications: reducing dietary salt intake to less than 6 g per day, eating a balanced diet rich in fruit, vegetables, and wholegrains, maintaining a healthy weight, engaging in at least 150 minutes of moderate-intensity physical activity per week, limiting alcohol consumption to no more than 14 units per week, and stopping smoking.

When lifestyle changes alone are insufficient, antihypertensive medication is introduced according to the NICE stepped-care approach.

How indapamide works: mechanism of action

Indapamide exerts its antihypertensive effect through two complementary mechanisms. First, it acts on the distal convoluted tubule of the nephron in the kidney, inhibiting the sodium-chloride co-transporter.

This prevents the reabsorption of sodium and chloride from the tubular fluid back into the blood, causing increased urinary excretion of sodium, chloride, and water.

The resulting reduction in extracellular fluid volume and plasma volume lowers cardiac output and blood pressure.

Second, at the doses used clinically for hypertension (1.5 mg modified-release or 2.5 mg standard-release), indapamide produces a direct vasodilatory effect on arterial smooth muscle.

This is thought to be mediated by a reduction in intracellular calcium availability and an increase in the local production of vasodilatory prostaglandins, particularly prostacyclin (PGI2).

The combination of reduced blood volume and lower peripheral vascular resistance produces sustained blood pressure reduction over 24 hours.

Unlike loop diuretics such as furosemide, which produce a rapid and pronounced diuresis, indapamide at therapeutic doses has a relatively mild diuretic effect.

The blood pressure-lowering action predominates, making it suitable for long-term antihypertensive therapy without significant fluid depletion.

This also means that patients typically experience less frequent urination than they might expect from a medicine described as a diuretic.

Clinical evidence and UK prescribing guidance

Indapamide has a robust evidence base supporting its use in hypertension.

The HYVET (Hypertension in the Very Elderly Trial) demonstrated that indapamide-based treatment in patients aged 80 and over significantly reduced the incidence of stroke, heart failure, and all-cause mortality compared with placebo.

The PROGRESS (Perindopril Protection Against Recurrent Stroke Study) showed that combining indapamide with the ACE inhibitor perindopril reduced the risk of recurrent stroke by 43% in patients with a history of cerebrovascular disease.

The ADVANCE (Action in Diabetes and Vascular Disease) trial found that the fixed-dose combination of indapamide and perindopril reduced the risk of major cardiovascular events and all-cause mortality in patients with type 2 diabetes.

NICE guideline NG136 recommends thiazide-like diuretics (specifically indapamide or chlorthalidone in preference to conventional thiazides) as step 1 treatment in hypertensive patients aged 55 and over, or in patients of Black African or African-Caribbean descent at any age.

For patients already taking an ACE inhibitor or angiotensin receptor blocker (ARB), a thiazide-like diuretic or calcium channel blocker is recommended as step 2 add-on therapy.

At step 3, the combination of an ACE inhibitor or ARB, a calcium channel blocker, and a thiazide-like diuretic is suggested.

The BNF specifically notes that indapamide is preferred over older thiazides for hypertension because of its more favourable metabolic profile.

The choice of indapamide over bendroflumethiazide reflects current evidence that thiazide-like diuretics have better cardiovascular outcome data and fewer adverse metabolic effects.

Bendroflumethiazide remains widely prescribed in the UK for historical reasons, but new initiations are increasingly in favour of indapamide or chlorthalidone.

Indapamide compared with other diuretics and antihypertensives

Understanding how indapamide compares with other blood pressure-lowering medicines helps put its role in context.

Bendroflumethiazide, the most commonly prescribed thiazide in the UK, is effective but has more pronounced effects on blood glucose, lipids, and uric acid than indapamide.

Chlorthalidone is another thiazide-like diuretic with strong outcome data (from the ALLHAT trial) and a longer duration of action than indapamide; it is an alternative first-line option but is less widely prescribed in UK general practice.

ACE inhibitors (such as ramipril and lisinopril) and ARBs (such as losartan and candesartan) are recommended as step 1 therapy for patients under 55 who are not of Black African or African-Caribbean descent.

Calcium channel blockers (such as amlodipine and felodipine) are another step 1 option for patients aged 55 and over.

The choice among these classes depends on the patient's age, ethnicity, comorbidities, and individual tolerability.

In practice, many patients with hypertension require two or more medicines in combination to achieve their blood pressure target.

Loop diuretics (furosemide and bumetanide) are not typically used for hypertension management.

They are reserved for conditions that require significant fluid removal, such as heart failure, nephrotic syndrome, and acute pulmonary oedema.

Potassium-sparing diuretics (spironolactone, amiloride) are used in specific situations, including resistant hypertension (NICE recommends spironolactone as step 4 treatment) and hyperaldosteronism.

Dosage and administration

Indapamide is taken once daily, preferably in the morning. The standard-release formulation provides 2.5 mg, while the modified-release formulation (Natrilix SR) provides 1.5 mg. These are not interchangeable.

The modified-release tablet is designed to deliver indapamide gradually over 24 hours, producing smoother blood pressure control and potentially fewer electrolyte disturbances.

Swallow the tablet whole with a glass of water. Do not crush, chew, or divide modified-release tablets.

There is no benefit to increasing the dose of indapamide above the recommended amount.

Higher doses produce more pronounced diuresis and greater electrolyte loss without additional blood pressure lowering.

If indapamide alone does not achieve your blood pressure target, your prescriber will add a second antihypertensive medicine rather than increase the indapamide dose.

Indapamide is effective in patients with normal or mildly impaired kidney function (eGFR above 30 mL/min).

As kidney function declines, the efficacy of thiazide-like diuretics diminishes, and a loop diuretic may be substituted.

In patients with liver disease, indapamide should be used with caution because of the risk of precipitating hepatic encephalopathy.

Side effects of indapamide

Electrolyte and metabolic effects

The most clinically significant adverse effects of indapamide are related to electrolyte disturbances. Hypokalaemia (low potassium) can cause muscle weakness, cramps, fatigue, constipation, and palpitations.

Severe hypokalaemia increases the risk of potentially dangerous heart rhythm disturbances.

The risk of hypokalaemia is lower with indapamide (particularly the 1.5 mg modified-release dose) than with conventional thiazides, but potassium levels should be monitored regularly.

Eating potassium-rich foods such as bananas, oranges, tomatoes, and leafy green vegetables can help maintain normal levels, though potassium supplements should not be taken without medical advice.

Hyponatraemia (low sodium) is a particularly important risk in older adults and can present with nonspecific symptoms including confusion, drowsiness, nausea, headache, lethargy, and unsteadiness.

In severe cases, hyponatraemia may cause seizures and requires hospital admission. If you develop any of these symptoms, contact your GP promptly or call NHS 111.

Mild elevations in blood glucose may occur, which is relevant for patients with diabetes or prediabetes. Uric acid levels may rise, potentially triggering gout in susceptible individuals. These metabolic effects are less pronounced with indapamide than with older thiazides.

Other common and uncommon side effects

Headache, dizziness, and fatigue are commonly reported. Gastrointestinal symptoms including nausea, constipation, and dry mouth occur in some patients.

Skin reactions, including maculopapular rashes and photosensitivity, have been described.

Postural hypotension (dizziness on standing) may occur, particularly in the first few days of treatment or in elderly patients.

Rare and very rare side effects

Rare effects include thrombocytopaenia, leucopaenia, agranulocytosis, aplastic anaemia, haemolytic anaemia, pancreatitis, hepatitis, and severe hypersensitivity reactions including angioedema and Stevens-Johnson syndrome.

Very rarely, QT interval prolongation has been reported in association with severe electrolyte depletion.

Seek immediate medical attention if you develop unexplained bruising or bleeding, sore throat with fever, severe abdominal pain, yellowing of the skin or eyes, or swelling of the face, lips, or tongue.

When to seek urgent medical advice

Contact your GP or call NHS 111 if you experience persistent dizziness, confusion, drowsiness, muscle cramps, palpitations, or a skin rash.

Call 999 or attend A&E if you develop signs of a severe allergic reaction (swelling of the face or throat, difficulty breathing), signs of a stroke (facial drooping, arm weakness, speech difficulty), signs of a heart attack (chest pain radiating to arm or jaw), or collapse.

Report any suspected adverse reactions to the MHRA at yellowcard.mhra.gov.uk .

Warnings and precautions

Contraindications

Indapamide must not be used in patients with known hypersensitivity to indapamide, other sulfonamide-derived drugs, or any excipient. It is contraindicated in severe hepatic impairment (including hepatic encephalopathy), severe renal impairment (eGFR below 30 mL/min), and uncorrected hypokalaemia.

Monitoring requirements

Baseline blood tests should include serum sodium, potassium, calcium, urea, creatinine (with estimated eGFR), glucose, uric acid, and a lipid profile.

Electrolytes and kidney function should be rechecked within 4 to 6 weeks of starting treatment and at least annually thereafter.

More frequent monitoring is recommended in elderly patients, patients taking other medications that affect electrolytes (such as ACE inhibitors, ARBs, or digoxin), and patients with renal impairment.

Drug interactions

NSAIDs (ibuprofen, naproxen, diclofenac) can reduce the blood pressure-lowering effect of indapamide and increase the risk of kidney injury.

Lithium clearance is reduced by thiazide-like diuretics, and concurrent use can lead to lithium toxicity; this combination should be avoided or used with intensive monitoring of lithium levels.

The concurrent use of indapamide with other drugs that lower potassium (loop diuretics, corticosteroids, stimulant laxatives) increases the risk of hypokalaemia.

Drugs that prolong the QT interval should be used cautiously with indapamide because hypokalaemia magnifies this risk.

Pregnancy and breastfeeding

Indapamide is not recommended during pregnancy. Diuretics can reduce uteroplacental perfusion and are not appropriate for the treatment of gestational hypertension or pre-eclampsia.

Alternative antihypertensives with established safety in pregnancy include labetalol, methyldopa, and nifedipine modified-release. Indapamide passes into breast milk, and breastfeeding is not recommended during treatment.

How to get indapamide in the UK

Indapamide is a prescription-only medicine available through the NHS.

Your GP can prescribe it following a clinical assessment that includes blood pressure measurement, blood tests (kidney function, electrolytes), and cardiovascular risk evaluation.

Authorised online prescribers registered with the General Pharmaceutical Council (GPhC) can also prescribe indapamide after an appropriate clinical consultation.

The standard NHS prescription charge in England is currently 9.90 pounds per item; prescriptions are free in Scotland, Wales, and Northern Ireland.

Generic indapamide is widely available and inexpensive.

Living with hypertension: lifestyle advice alongside indapamide

Medication is one component of blood pressure management. NICE recommends combining drug treatment with sustained lifestyle changes for optimal cardiovascular risk reduction.

Reduce your salt intake to less than 6 g per day (about one teaspoon) by avoiding processed foods, ready meals, and adding less salt during cooking.

Aim for at least five portions of fruit and vegetables per day.

Maintain a healthy weight: losing even 5 to 10% of your body weight if overweight can meaningfully lower blood pressure.

Exercise regularly, aiming for at least 150 minutes of moderate-intensity activity per week (brisk walking, cycling, swimming).

Limit alcohol to no more than 14 units per week, spread across at least three days. Stop smoking: smoking raises blood pressure acutely and accelerates atherosclerosis.

Home blood pressure monitoring is encouraged by NICE and helps you and your GP track the effectiveness of treatment.

Use a validated monitor on the upper arm, take readings at the same time each day (before medication), and record them for review at appointments.

Aim for home readings consistently below 135/85 mmHg (or below 130/80 mmHg if you have diabetes or chronic kidney disease).

Sources

Medical information

Indapamide is classified as a thiazide-like diuretic, meaning it acts at the same site in the kidney as conventional thiazides (the distal convoluted tubule) but has a distinct chemical structure based on an indoline ring rather than the benzothiadiazine backbone of true thiazides. It inhibits sodium reabsorption at the cortical diluting segment of the nephron, promoting the excretion of sodium, chloride, and water. At lower doses, indapamide also produces direct vasodilatation by reducing vascular smooth muscle calcium influx and enhancing prostacyclin synthesis, contributing to blood pressure reduction independently of its diuretic effect. Compared with bendroflumethiazide and hydrochlorothiazide, indapamide causes less disturbance of glucose metabolism, lipid profiles, and uric acid levels at therapeutic doses. It is a prescription-only medicine classified as POM in the United Kingdom.

Dosage guidance

The usual dose of indapamide for hypertension depends on the formulation. For standard-release tablets, the dose is 2.5 mg once daily, taken in the morning. For modified-release tablets (Natrilix SR), the dose is 1.5 mg once daily, also taken in the morning. The two formulations are not interchangeable on a milligram-for-milligram basis because the modified-release preparation provides a different pharmacokinetic profile. Swallow the tablet whole with water. Do not crush or chew modified-release tablets. Taking the dose in the morning helps avoid having to get up during the night to pass urine, although indapamide generally produces less pronounced diuresis than loop diuretics such as furosemide. No dose adjustment is required for mild to moderate renal impairment (eGFR above 30 mL/min). Indapamide becomes less effective as kidney function declines and is generally considered ineffective in severe renal impairment (eGFR below 30 mL/min). In this setting, a loop diuretic is usually more appropriate. Indapamide is hepatically metabolised and should be used with caution in patients with significant liver disease. Elderly patients may be started on the same dose but should be monitored more closely for electrolyte imbalances, particularly low sodium (hyponatraemia) and low potassium (hypokalaemia). Your prescriber will arrange blood tests to check your kidney function and electrolytes before starting treatment and at regular intervals thereafter. Do not increase the dose beyond the recommended amount, as higher doses do not produce greater blood pressure reduction and increase the risk of metabolic side effects. If blood pressure is not adequately controlled with indapamide alone, your prescriber may add another antihypertensive rather than increasing the indapamide dose. If you miss a dose, take it as soon as you remember unless it is late in the day. Do not take a double dose to make up for a missed one.

Side effects and warnings

Common side effects of indapamide include headache, dizziness, fatigue, and gastrointestinal disturbances such as nausea, constipation, and dry mouth. Skin rashes, including maculopapular eruptions and purpura, have been reported. The most clinically significant side effects relate to electrolyte and metabolic disturbances. Hypokalaemia (low potassium) is the most important and can cause muscle weakness, cramps, fatigue, palpitations, and, in severe cases, cardiac arrhythmias. The risk of hypokalaemia is lower with indapamide than with conventional thiazide diuretics, particularly at the 1.5 mg modified-release dose, but monitoring remains important. Hyponatraemia (low sodium) is another recognised risk, particularly in elderly patients, and can present with confusion, drowsiness, nausea, and falls. Severe hyponatraemia can cause seizures and requires urgent medical attention. Other metabolic effects include mild elevations in blood glucose, uric acid (which may precipitate gout in susceptible individuals), and, rarely, alterations in lipid levels. These effects are generally less pronounced with indapamide than with bendroflumethiazide. Uncommon side effects include postural hypotension (a drop in blood pressure on standing, causing dizziness or light-headedness), photosensitivity (increased sensitivity of the skin to sunlight), and allergic skin reactions. Rare effects include thrombocytopaenia (low platelet count), leucopaenia (low white blood cell count), agranulocytosis, aplastic anaemia, pancreatitis, and hepatic dysfunction. Very rarely, QT interval prolongation has been reported in association with severe hypokalaemia, which underscores the importance of electrolyte monitoring. Report any suspected adverse reactions to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk.

Indapamide is contraindicated in patients with known hypersensitivity to indapamide, other sulfonamide-derived drugs, or any excipient in the formulation.

It must not be used in patients with severe hepatic impairment (including hepatic encephalopathy), severe renal impairment (eGFR below 30 mL/min where the drug is ineffective), or hypokalaemia.

Before starting indapamide, your prescriber should check your kidney function (eGFR), serum electrolytes (sodium, potassium, calcium), blood glucose, uric acid, and lipid profile.

These tests should be repeated within 4 to 6 weeks of starting treatment and at regular intervals thereafter.

Elderly patients require particularly close monitoring, as they are more susceptible to hyponatraemia. Patients with diabetes may experience slightly impaired glucose tolerance.

Blood glucose should be monitored more frequently in diabetic patients taking indapamide, and antidiabetic medication may require dose adjustment.

Patients with a history of gout should be aware that indapamide can raise uric acid levels and potentially trigger acute gouty attacks. Adequate fluid intake is recommended.

Indapamide may potentiate the effects of other antihypertensive medicines, increasing the risk of hypotension.

Concurrent use with NSAIDs (such as ibuprofen and naproxen) may reduce the antihypertensive effect and increase the risk of renal impairment.

Lithium levels may rise during concurrent use with indapamide, and close monitoring is essential; this combination should generally be avoided.

The concurrent use of indapamide with drugs that prolong the QT interval (such as certain antiarrhythmics, antipsychotics, and macrolide antibiotics) requires caution, particularly if hypokalaemia is present.

Indapamide is not recommended during pregnancy, as diuretics can reduce placental perfusion and are not first-line treatments for gestational hypertension.

It is excreted in breast milk and should be avoided during breastfeeding. Inform your prescriber of all medicines you are taking, including over-the-counter products and herbal remedies.

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