Bisoprolol

Bisoprolol is a highly beta 1 selective blocker with balanced renal and hepatic clearance and a long half life. It is used in hypertension, angina and chronic heart failure with reduced ejection fraction. Titration in heart failure is slow.

Classification. Highly cardioselective beta 1 blocker; no intrinsic sympathomimetic activity.

Mechanism. Blocks beta 1 receptors, lowering heart rate, contractility and renin release. Little effect on beta 2 receptors at therapeutic doses.

Pharmacodynamics. Heart rate falls within 1 to 2 hours; effect lasts 24 hours. Reduces mortality and hospital admission in heart failure with reduced ejection fraction.

Pharmacokinetics. Oral bioavailability about 90%; little first pass metabolism. Half life 10 to 12 hours. About half is excreted unchanged in urine and half is metabolised in the liver.

Hypertension and angina, adult.

• Start 2.5 to 5 mg once daily in the morning.

• Usual maintenance 5 to 10 mg once daily.

• Maximum 20 mg daily; doses over 10 mg rarely add benefit.

Heart failure with reduced ejection fraction, adult.

• Start 1.25 mg once daily for 1 week in a stable patient.

• Increase every 1 to 4 weeks: 2.5, 3.75, 5, 7.5, then 10 mg once daily, as tolerated.

• Target and maximum 10 mg once daily.

• Add to an angiotensin converting enzyme inhibitor and diuretic once euvolaemic.

Rate control in atrial fibrillation (off label), adult. 2.5 to 10 mg once daily.

Children. Not established; specialist use.

Contraindications. Acute heart failure or decompensation requiring inotropes; cardiogenic shock; second or third degree atrioventricular block; sick sinus syndrome; sino-atrial block; symptomatic bradycardia (under 60/min before treatment); symptomatic hypotension; severe asthma; severe peripheral arterial disease; untreated phaeochromocytoma; metabolic acidosis.

Warnings. Do not stop abruptly. Masks hypoglycaemia. May worsen psoriasis and peripheral arterial disease. Caution in asthma. First dose bradycardia.

Adverse effects. Fatigue, dizziness, bradycardia, cold extremities, headache, gastrointestinal upset, sleep disturbance, erectile dysfunction, heart failure worsening.

Interactions. Verapamil and diltiazem: bradycardia and heart block. Digoxin and amiodarone: bradycardia. Clonidine: rebound hypertension. Rifampicin shortens half life moderately. Insulin and sulphonylureas: masked hypoglycaemia. Non steroidal anti-inflammatory drugs oppose the effect.

Special groups.

• Pregnancy: avoid if possible; foetal growth restriction and neonatal bradycardia.

• Breastfeeding: avoid; limited data.

• Older adults: start low; monitor pulse.

• Kidney impairment: creatinine clearance under 20 mL/min: maximum 10 mg daily.

• Liver impairment: severe: maximum 10 mg daily.

Formulations. Tablets 1.25, 2.5, 3.75, 5, 7.5, 10 mg.

Administration. Oral once daily in the morning, with or without food. Swallow with water; do not chew.

Baseline. Pulse, blood pressure, ECG, renal and liver function, volume status and weight in heart failure.

Monitoring. Heart rate and blood pressure before each titration step; weight, oedema and symptoms in heart failure; electrolytes and renal function.

Stopping. Taper over 1 to 2 weeks, particularly in ischaemic heart disease.

Common prescribing errors. Starting at 5 mg in heart failure; skipping titration steps; using it in asthma; stopping suddenly.