Nebivolol

Nebivolol is a highly beta 1 selective blocker with nitric oxide mediated vasodilation. It is used in hypertension and in heart failure in older adults. It is not stocked in many East African markets.

Classification. Highly cardioselective beta 1 blocker with endothelial nitric oxide releasing effect; racemic mixture.

Mechanism. The d isomer blocks beta 1 receptors; the l isomer promotes endothelial nitric oxide release, causing vasodilation and lowering peripheral resistance.

Pharmacodynamics. Lowers blood pressure with little change in resting cardiac output and less fatigue and erectile dysfunction than older beta blockers. Heart rate falls modestly.

Pharmacokinetics. Bioavailability varies with CYP2D6 phenotype (about 12% in extensive and 96% in poor metabolisers). Half life 12 hours in extensive metabolisers and 19 hours or more in poor metabolisers. Hepatic metabolism; excreted in urine and faeces.

Hypertension, adult.

• Start 5 mg once daily.

• Increase after 2 weeks if needed to 10 mg once daily; some markets allow doses to 40 mg daily, with little added effect.

• Start 2.5 mg in older adults, in creatinine clearance under 30 mL/min, and in moderate hepatic impairment.

Heart failure, stable, adults 70 years and over.

• Start 1.25 mg once daily for 1 to 2 weeks.

• Increase to 2.5 mg, then 5 mg, then 10 mg once daily at 1 to 2 week intervals.

• Target and maximum 10 mg once daily.

Children. Not established.

Contraindications. Hypersensitivity; sick sinus syndrome; second or third degree atrioventricular block; severe bradycardia; cardiogenic shock; acute or decompensated heart failure needing inotropes; severe hepatic impairment; bronchospasm; untreated phaeochromocytoma; metabolic acidosis.

Warnings. Do not stop abruptly. Masks hypoglycaemia. Caution in asthma, peripheral arterial disease and psoriasis.

Adverse effects. Headache, fatigue, dizziness, paraesthesia, bradycardia, dyspnoea, oedema, nausea, diarrhoea.

Interactions. CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine) raise levels. Verapamil and diltiazem: bradycardia and heart block. Digoxin and amiodarone: bradycardia. Clonidine: rebound hypertension on withdrawal. Insulin and sulphonylureas: masked hypoglycaemia.

Special groups.

• Pregnancy: avoid; no adequate data.

• Breastfeeding: avoid; excreted in milk in animals.

• Older adults: start low.

• Kidney impairment: creatinine clearance under 30 mL/min: start 2.5 mg and titrate carefully.

• Liver impairment: moderate: start 2.5 mg; severe: avoid.

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

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

Baseline. Pulse, blood pressure, ECG, liver and kidney function, airway history.

Monitoring. Heart rate and blood pressure at each dose change; weight and fluid status in heart failure.

Stopping. Taper over 1 to 2 weeks.

Common prescribing errors. Starting at 5 mg in an older adult with kidney impairment; stopping suddenly; combining with a CYP2D6 inhibitor without monitoring.