Candesartan

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Candesartan on Prescriptsy

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Candesartan cilexetil is an angiotensin II receptor blocker (ARB) widely prescribed in the United Kingdom for the treatment of essential hypertension and chronic heart failure with reduced left ventricular systolic function.

Hypertension affects approximately 1 in 3 adults in England and is the single largest modifiable risk factor for cardiovascular disease, stroke, and chronic kidney disease.

Candesartan lowers blood pressure by blocking the action of angiotensin II, a potent vasoconstrictor hormone, at its AT1 receptor in blood vessel walls, the adrenal glands, and the kidneys.

Candesartan is also licensed for the treatment of heart failure (NYHA class II to IV) in patients with impaired left ventricular systolic function (ejection fraction 40% or less), as an alternative or add-on to ACE inhibitor therapy.

This page provides a comprehensive clinical overview of how candesartan works, dosing for hypertension and heart failure, side effects, important safety warnings, and how to obtain a prescription in the UK.

Important safety information about candesartan

Before reading further, note the following critical safety points about candesartan.

• Candesartan must not be used during pregnancy, especially during the second and third trimesters. It can cause serious harm to the developing baby, including kidney failure, low amniotic fluid, and death.
• Blood tests for kidney function and potassium must be performed before starting treatment, after dose changes, and regularly during ongoing therapy.
• Do not take candesartan with aliskiren if you have diabetes or moderate to severe kidney disease.
• Seek emergency medical help if you develop swelling of the face, lips, tongue, or throat (angioedema).

Understanding hypertension

Blood pressure is the force exerted by circulating blood on the walls of arteries.

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

Normal blood pressure in adults is below 140/90 mmHg when measured in a clinic setting, or below 135/85 mmHg when measured at home or by ambulatory monitoring.

Hypertension is persistently elevated blood pressure.

It is classified by NICE as stage 1 (clinic reading 140/90 to 159/99 mmHg), stage 2 (clinic reading 160/100 mmHg or higher), or severe (clinic reading 180/120 mmHg or higher).

Most hypertension has no identifiable cause and is termed essential or primary hypertension.

Secondary causes (renal artery stenosis, phaeochromocytoma, Cushing syndrome, primary hyperaldosteronism) account for a minority of cases but should be excluded in resistant or atypical presentations.

Hypertension is usually asymptomatic and is often detected incidentally during routine health checks.

Uncontrolled hypertension progressively damages the heart, brain, kidneys, and blood vessels, increasing the lifetime risk of myocardial infarction, stroke, heart failure, chronic kidney disease, peripheral arterial disease, and vascular dementia.

Treatment with antihypertensive medicines reduces these risks substantially.

How candesartan works: mechanism of action

Candesartan cilexetil is a prodrug that is rapidly hydrolysed to the active moiety candesartan during absorption from the gastrointestinal tract.

Candesartan is a highly selective, insurmountable antagonist of the angiotensin II type 1 (AT1) receptor.

Angiotensin II is the primary effector peptide of the renin-angiotensin-aldosterone system (RAAS) and mediates its cardiovascular effects through the AT1 receptor.

By blocking the AT1 receptor, candesartan inhibits the following angiotensin II-mediated effects: vasoconstriction of arterioles and venules, stimulation of aldosterone secretion from the adrenal cortex (leading to sodium and water retention), promotion of sympathetic nervous system activity, stimulation of cardiac and vascular smooth muscle cell hypertrophy and fibrosis, and renal sodium reabsorption.

The result is peripheral vasodilation, reduced circulating volume, lower blood pressure, and reduced cardiac workload.

Unlike ACE inhibitors (which block the enzyme that converts angiotensin I to angiotensin II), ARBs act downstream at the receptor level.

This means that angiotensin II produced via non-ACE pathways (such as chymase) is also effectively blocked.

Importantly, candesartan does not inhibit the breakdown of bradykinin, which is the mechanism responsible for the persistent dry cough associated with ACE inhibitors in approximately 5 to 20% of patients.

This makes candesartan a well-tolerated alternative for patients who are intolerant of ACE inhibitors due to cough.

Clinical evidence for candesartan

Hypertension

The antihypertensive efficacy of candesartan has been demonstrated in numerous randomised controlled trials.

The SCOPE (Study on Cognition and Prognosis in the Elderly) trial enrolled over 4,900 elderly patients with hypertension and showed that candesartan-based treatment reduced the risk of non-fatal stroke by 28% compared with placebo (with open-label antihypertensive therapy added as needed).

Candesartan was well tolerated with a side-effect profile comparable to placebo.

NICE Guideline NG136 (Hypertension in adults: diagnosis and management) recommends ARBs as a first-line option for hypertension in patients aged under 55 and as an alternative to ACE inhibitors across all age groups when ACE inhibitor intolerance (most commonly cough) occurs.

Step 1 treatment for younger patients or those with diabetes is an ACE inhibitor or ARB; for older patients or Black patients of African or Caribbean origin, a calcium channel blocker is recommended first line, with an ARB or ACE inhibitor added at step 2.

Heart failure

The CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity) programme comprised three pivotal trials.

CHARM-Alternative demonstrated that candesartan reduced the combined endpoint of cardiovascular death or heart failure hospitalisation by 23% in patients intolerant of ACE inhibitors.

CHARM-Added showed that adding candesartan to existing ACE inhibitor therapy further reduced cardiovascular death and heart failure hospitalisation.

CHARM-Preserved explored candesartan in heart failure with preserved ejection fraction, with a trend toward benefit that did not reach statistical significance.

NICE Guideline NG106 (Chronic heart failure in adults: diagnosis and management) recommends an ARB as an alternative to an ACE inhibitor for patients with heart failure with reduced ejection fraction who are intolerant of ACE inhibitors.

Candesartan is one of the ARBs with the strongest evidence base in heart failure.

Dosage and administration

Candesartan is taken orally once daily, with or without food, at any consistent time of day.

It is available as tablets in strengths of 2 mg, 4 mg, 8 mg, 16 mg, and 32 mg.

An oral solution is available for paediatric use or for patients who have difficulty swallowing tablets.

Hypertension dosing

The recommended starting dose for most adults is 8 mg once daily.

If blood pressure remains inadequately controlled after 4 weeks, the dose may be increased to 16 mg once daily.

The maximum dose is 32 mg once daily, although most patients achieve adequate control at 8 to 16 mg.

For patients at risk of hypotension (those on high-dose diuretics or with intravascular volume depletion), a lower starting dose of 4 mg may be appropriate.

Heart failure dosing

The recommended starting dose in heart failure is 4 mg once daily.

The dose is doubled at intervals of at least 2 weeks, guided by blood pressure, renal function, and serum potassium, to a target dose of 32 mg once daily.

If the target dose is not tolerated, the highest tolerated dose should be maintained.

Dose titration in heart failure requires close monitoring and should be supervised by a clinician experienced in heart failure management.

Special populations

No dose adjustment is required for mild to moderate renal impairment or mild to moderate hepatic impairment. Candesartan is contraindicated in severe hepatic impairment or cholestasis.

In severe renal impairment (eGFR below 15 mL/min), experience is limited and caution is advised.

Paediatric dosing depends on age and weight and should follow BNF for Children guidance.

Side effects of candesartan

Common side effects

Candesartan is generally well tolerated. In hypertension trials, the incidence of adverse events was similar to placebo.

Dizziness, headache, and upper respiratory tract infections were the most commonly reported symptoms.

In heart failure trials, hypotension (low blood pressure), hyperkalaemia (elevated potassium), and renal function deterioration were more frequently observed, particularly during dose escalation.

Important laboratory abnormalities

Hyperkalaemia is a clinically significant risk, especially in patients with renal impairment, diabetes mellitus, heart failure, or those taking other medicines that raise potassium levels (potassium-sparing diuretics such as spironolactone, potassium supplements, trimethoprim, or heparin).

Serum potassium should be monitored before starting candesartan, after dose changes, and regularly during treatment. Elevated potassium can cause cardiac arrhythmias and requires prompt management.

Increases in serum creatinine may occur, particularly in patients with pre-existing renal impairment or heart failure. Small rises (up to 30% from baseline) are expected and generally acceptable.

Larger rises or progressive deterioration in renal function should prompt investigation for renal artery stenosis, volume depletion, or other reversible causes.

Rare but serious side effects

Angioedema has been reported very rarely with candesartan. Symptoms include rapid swelling of the face, lips, tongue, throat, or extremities.

Angioedema can compromise the airway and is a medical emergency. If you develop these symptoms, stop candesartan immediately and call 999.

Patients with a history of angioedema with any medicine (including ACE inhibitors) may be at higher risk and should be counselled accordingly.

When to seek medical advice

Contact your GP or call NHS 111 if you experience persistent dizziness, fainting, palpitations, unexplained muscle weakness, or reduced urine output.

Call 999 or attend A&E immediately if you develop swelling of the face, lips, tongue, or throat, or difficulty breathing.

Report any suspected adverse reactions via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk .

Warnings and precautions

Pregnancy and breastfeeding

Candesartan is contraindicated during pregnancy. Use during the second and third trimesters has been associated with foetotoxicity, including renal failure, oligohydramnios, skull ossification defects, and neonatal death.

Use during the first trimester is also not recommended. Women of childbearing potential must use effective contraception.

If pregnancy is confirmed, discontinue candesartan immediately and switch to a pregnancy-safe alternative under obstetric guidance.

Candesartan is not recommended during breastfeeding, as it is unknown whether it passes into breast milk.

Dual renin-angiotensin system blockade

Concomitant use of candesartan with an ACE inhibitor or aliskiren increases the risk of hyperkalaemia, hypotension, and acute kidney injury.

The combination of candesartan with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (eGFR below 60 mL/min).

The combination of an ARB with an ACE inhibitor is not routinely recommended and should be considered only in specialist heart failure settings with close monitoring.

First-dose hypotension

Symptomatic hypotension may occur at treatment initiation, particularly in patients with volume depletion (from high-dose diuretics, salt restriction, diarrhoea, or vomiting), heart failure, or severe hypertension.

Volume status should be assessed and corrected before starting candesartan. A lower starting dose (4 mg) should be used in at-risk patients.

Renal artery stenosis

ARBs can precipitate acute renal failure in patients with bilateral renal artery stenosis or stenosis of a solitary functioning kidney. Renal function should be monitored closely in patients with suspected renovascular disease.

How to get a candesartan prescription in the UK

Candesartan is classified as a prescription-only medicine (POM) in the United Kingdom. It is commonly prescribed by GPs, cardiologists, and hypertension or heart failure specialists.

Before initiating treatment, your GP will typically measure your blood pressure on at least two occasions, perform blood tests (including renal function and electrolytes), and assess your overall cardiovascular risk.

If you are already taking an ACE inhibitor and experiencing side effects (particularly a persistent dry cough), your GP can switch you to candesartan as a well-tolerated alternative.

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

Generic candesartan is widely available and is significantly less expensive than branded alternatives.

Living with hypertension: complementary lifestyle measures

Whilst candesartan effectively lowers blood pressure pharmacologically, lifestyle modifications play an important complementary role.

NICE recommends reducing salt intake to less than 6 g per day, maintaining a healthy body weight (BMI 18.5 to 24.9), taking regular physical activity (at least 150 minutes of moderate-intensity exercise per week), limiting alcohol to no more than 14 units per week, eating a balanced diet rich in fruit, vegetables, and wholegrains, and managing stress.

Smoking cessation is essential for overall cardiovascular risk reduction, although it does not directly lower blood pressure.

Home blood pressure monitoring is recommended by NICE for confirming the diagnosis of hypertension and for ongoing monitoring of treatment response. Validated, automated upper-arm monitors are preferred.

Your GP practice or pharmacist can advise on suitable devices and correct measurement technique.

When to seek urgent medical advice

Contact your GP or call NHS 111 if you experience persistent dizziness, lightheadedness, or fainting, which may indicate blood pressure that is too low.

Seek emergency medical attention (call 999 or attend A&E) if you develop chest pain, sudden weakness or numbness on one side of the body, difficulty speaking, sudden severe headache, or swelling of the face, lips, tongue, or throat.

These may indicate a cardiovascular emergency or angioedema. Report any suspected adverse reactions via the MHRA Yellow Card scheme at yellowcard.mhra.gov.uk .

Sources

• Candesartan cilexetil Tablets, Summary of Product Characteristics (EMC)
• Candesartan cilexetil, British National Formulary (BNF)
• NICE NG136: Hypertension in adults, diagnosis and management
• NICE NG106: Chronic heart failure in adults, diagnosis and management
• High blood pressure (hypertension), NHS
• Heart failure, NHS
• MHRA Yellow Card Scheme