Candesartan
Atacand · Candesartan Sandoz · Candesartan Krka · Candemox
Prodrug hydrolysed to candesartan during absorption that binds the AT₁-receptor tightly and slowly reversibly — hence the even effect over 24 hours with once-daily dosing. The ARB that together with valsartan has documented mortality benefit in heart failure (CHARM), and the first choice when an ACE inhibitor must be switched due to cough. The target dose in heart failure is 32 mg — four times the usual hypertension dose.
Contraindicated during pregnancy — foetotoxic in the second and third trimesters. Causes hyperkalaemia and creatinine rise in the same way as an ACE inhibitor; the absence of cough does not mean kidneys and potassium need less monitoring.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Heart failure (HFrEF) | 4 mg orally daily, doubled at intervals of at least 2 weeks to 32 mg | target dose 32 mg, otherwise highest tolerated |
| Hypertension | 8 mg orally daily, increased as needed to 16 mg and at most 32 mg | 4 mg in hypovolaemia or renal impairment |
| Switch from ACE inhibitor for cough | 8 mg orally daily, equivalent titration thereafter | the cough resolves within 1–4 weeks |
| Hypertension in children 6–17 years | 4 mg daily; max 8 mg at < 50 kg, 16 mg at ≥ 50 kg | by a paediatric cardiologist or paediatric nephrologist |
| Insufficient effect with monotherapy | candesartan 16–32 mg + hydrochlorothiazide 12,5 mg | combination tablet available |
Starting dose 4 mg in mild to moderate renal impairment. Experience at eGFR < 15 ml/min is limited. A creatinine rise of up to 30 % and potassium up to 5,5 mmol/l after initiation is expected and not a reason to stop; with a larger rise, reduce the dose and investigate volume status, NSAIDs, and renal artery stenosis.
Starting dose 4 mg daily in mild to moderate hepatic impairment. Contraindicated in severe hepatic impairment and in cholestasis.
From 1 year of age: 4 mg daily as starting dose, maximum dose depending on body weight. Contraindicated below 1 year of age.
Do not combine with an ACE inhibitor and never add as a third RAAS drug on top of an ACE inhibitor and an MRA. Do not switch to candesartan after ACE inhibitor-induced angioedema without informing the patient — the risk of recurrence is low but not zero. In HFrEF, a patient who tolerates sacubitril/valsartan should have that instead of an ARB.
Pharmacokinetics
- BIOAVAIL.
- approximately 14 % (tablet)
- t½
- approximately 9 hours
- PROTEIN BINDING
- > 99 %
- METABOLISM
- Minimal, CYP2C9
- EXCRETION
- Unchanged via urine and bile
- PEAK CONC.
- 3–4 hours
- ONSET
- 2 hours · full effect 4 weeks
- DURATION
- > 24 hours