Candesartan

Candesartan cilexetil is a prodrug converted to candesartan, an angiotensin receptor blocker with tight receptor binding and a long duration. It treats hypertension and heart failure with reduced ejection fraction, with benefit shown in both reduced and preserved ejection fraction.

Classification. Angiotensin receptor blocker (AT1); prodrug.

Mechanism. Binds the AT1 receptor with slow dissociation, blocking vasoconstriction and aldosterone release.

Pharmacodynamics. Onset within 2 to 4 hours; full blood pressure effect over 4 weeks; duration over 24 hours. Reduces cardiovascular death and heart failure admission.

Pharmacokinetics. Bioavailability about 15% as candesartan; food has no effect. Half life about 9 hours. Cleared by urine (33%) and bile and faeces; not metabolised significantly by CYP enzymes.

Hypertension, adult.

• Start 8 mg once daily (4 mg if volume depleted, hepatic impairment or creatinine clearance under 30 mL/min).

• Increase after 4 weeks to 16 mg, then 32 mg once daily.

• Usual maintenance 8 to 16 mg; maximum 32 mg daily.

Heart failure with reduced ejection fraction, adult.

• Start 4 mg once daily (2 mg in older or frail patients).

• Double the dose every 2 weeks as tolerated.

• Target 32 mg once daily; maximum 32 mg daily.

Children. Aged 1 to under 6 years: 0.2 mg/kg once daily; aged 6 to 17 years and under 50 kg: 4 to 8 mg once daily; 50 kg and over: 8 to 16 mg once daily; maximum 16 mg (some labels 32 mg) daily. Specialist.

Contraindications. Pregnancy; bilateral renal artery stenosis; hyperkalaemia; severe hepatic impairment and cholestasis; hypersensitivity; aliskiren in diabetes or kidney impairment.

Warnings. Hypotension, hyperkalaemia and kidney function decline. Angioedema is rare. Sick day rule: hold during dehydrating illness. Take care when adding a mineralocorticoid antagonist.

Adverse effects. Dizziness, hypotension, hyperkalaemia, creatinine rise, headache, upper respiratory symptoms, rarely angioedema.

Interactions. Potassium supplements, potassium sparing diuretics, trimethoprim: hyperkalaemia. Non steroidal anti-inflammatory drugs: kidney injury. Lithium: toxicity. Other antihypertensives: additive hypotension.

Special groups.

• Pregnancy: contraindicated; stop when pregnancy is confirmed.

• Breastfeeding: avoid; no data.

• Patients of African ancestry: smaller response as monotherapy; combine with a calcium channel blocker or thiazide like diuretic.

• Older adults: start at 4 mg (2 mg in heart failure).

• Kidney impairment: creatinine clearance under 30 mL/min: start 4 mg; haemodialysis: not dialysable; monitor closely.

• Liver impairment: mild to moderate: start 4 mg; severe: avoid.

Formulations. Tablets 2, 4, 8, 16, 32 mg; combinations with hydrochlorothiazide.

Administration. Oral once daily at the same time, with or without food.

Baseline. Blood pressure, creatinine and eGFR, potassium, liver function, pregnancy status.

Monitoring. Creatinine and potassium 1 to 2 weeks after starting or each dose increase, then every 6 to 12 months. Accept a creatinine rise up to 30%; reduce or stop if over 30% or potassium is over 6.0 mmol/L; review contributors if potassium is over 5.5 mmol/L. Blood pressure and symptoms.

Stopping. Stop for pregnancy, angioedema, or creatinine rise over 30% or potassium over 6.0 mmol/L.

Common prescribing errors. Starting at 8 mg in volume depletion or kidney impairment; using it in pregnancy; omitting potassium and creatinine checks; combining with an angiotensin converting enzyme inhibitor without a clear indication.