Candesartan

Candesartan is an angiotensin II receptor blocker (ARB) that selectively blocks the AT1 receptor, preventing the vasoconstrictive, aldosterone-secreting, and sodium-retaining effects of angiotensin II.

This results in vasodilation, reduced blood pressure, decreased sodium retention, and regression of left ventricular hypertrophy.

Candesartan is licensed for the treatment of essential hypertension and for heart failure with reduced ejection fraction (HFrEF) in patients intolerant of ACE inhibitors.

The CHARM clinical trial programme demonstrated that candesartan reduced cardiovascular death and heart failure hospitalisations across a broad spectrum of heart failure patients.

NICE recommends ARBs as a first-line alternative to ACE inhibitors for hypertension (particularly in patients of African or Caribbean descent at any age, or all patients >55 years when calcium channel blockers are not tolerated) and for heart failure in ACE inhibitor-intolerant patients.

Candesartan is a prodrug (candesartan cilexetil) that is rapidly converted to the active form during absorption. Peak antihypertensive effect occurs within 4 weeks of initiation.

Take one tablet once daily at the same time each day, with or without food. Swallow whole with water. Continue taking candesartan even if you feel well, as hypertension is typically asymptomatic.

Do not stop abruptly without medical advice. Maintain adequate hydration, particularly during hot weather, illness, or exercise, as volume depletion increases the risk of hypotension.

If you experience dizziness or lightheadedness when standing, rise slowly from a seated or lying position.

Report any persistent dry cough, facial swelling, or difficulty breathing to your prescriber immediately (rare angioedema).

Hypertension: Start at 8 mg once daily. Usual maintenance dose: 8-16 mg once daily. Maximum: 32 mg once daily. In patients with intravascular volume depletion (e.g.

those on high-dose diuretics), start at 4 mg to reduce hypotension risk.

Heart failure: Start at 4 mg once daily. Double the dose at 2-week intervals as tolerated. Target dose: 32 mg once daily.

In mild-to-moderate hepatic impairment, start at 2 mg with careful dose titration. Candesartan is not recommended in severe hepatic impairment.

In renal impairment, no dose adjustment is needed for eGFR ≥15, though monitor potassium and creatinine closely. For eGFR <15, limited experience exists.

Side effects per SmPC frequency categories.

Common (≥1/100 to <1/10): Dizziness, headache, hypotension (particularly in heart failure patients during uptitration), hyperkalaemia, renal function impairment (elevated creatinine, especially in heart failure, bilateral renal artery stenosis, or combination with other RAAS inhibitors).

Uncommon (≥1/1,000 to <1/100): Back pain, nausea, elevated liver enzymes, hyponatraemia.

Very rare (<1/10,000): Angioedema, hepatitis, leucopenia, neutropenia, agranulocytosis, rash, urticaria, pruritus.

Hyperkalaemia is the most clinically important adverse effect and requires regular monitoring, particularly in patients with diabetes, renal impairment, or those taking potassium-sparing diuretics, potassium supplements, or other RAAS inhibitors.

Monitor renal function and serum potassium within 1-2 weeks of initiation and after each dose increase, particularly in heart failure, renal impairment, or concurrent diuretic use.

Dual RAAS blockade (combining an ARB with an ACE inhibitor or aliskiren) increases hypotension, hyperkalaemia, and renal impairment risk and is generally not recommended (ONTARGET trial data).

Candesartan may cause foetal harm and is absolutely contraindicated in pregnancy (second and third trimesters cause oligohydramnios, renal failure, and skull hypoplasia; first trimester data suggest risk).

Discontinue immediately upon confirmation of pregnancy. Patients with bilateral renal artery stenosis are at risk of acute renal failure; candesartan should not be used in this population.

Anaesthesiologists should be informed of candesartan use before surgery, as hypotension may occur under general anaesthesia.

Candesartan is contraindicated in patients with hypersensitivity to candesartan or any excipient, second and third trimester of pregnancy, severe hepatic impairment and/or cholestasis, concomitant use with aliskiren in patients with diabetes or renal impairment (eGFR <60 mL/min/1.

73m²). It should not be initiated in patients with bilateral renal artery stenosis or stenosis of a single functioning kidney.