Labetalol

Labetalol is a combined alpha 1 and non selective beta blocker used for hypertension in pregnancy and for acute severe hypertension. The ratio of beta to alpha blockade is about 3 to 1 orally and 7 to 1 intravenously. It lowers blood pressure without reflex tachycardia.

Classification. Combined alpha 1 and beta 1 and beta 2 adrenergic antagonist.

Mechanism. Alpha 1 blockade causes vasodilation; beta blockade slows heart rate and attenuates reflex tachycardia. Slight intrinsic sympathomimetic activity at beta 2 receptors contributes to vasodilation.

Pharmacodynamics. Oral onset 1 to 2 hours, peak 2 to 4 hours, duration 8 to 12 hours. IV onset 2 to 5 minutes, peak 5 to 15 minutes, duration 2 to 4 hours.

Pharmacokinetics. Oral bioavailability about 25% because of first pass metabolism, higher in liver disease and with food. Half life 6 to 8 hours. Hepatic glucuronidation; metabolites excreted in urine and bile. Crosses the placenta.

Hypertension, adult (including pregnancy).

• Start 100 mg orally twice daily with food.

• Increase every 2 days to 200 mg twice daily, then as needed.

• Usual maintenance 200 to 400 mg twice daily.

• Maximum 2.4 g daily in 2 to 3 divided doses (most patients need under 1.2 g).

Acute severe hypertension, adult (including pregnancy and postpartum).

• Bolus: 20 mg IV over 2 minutes, then 40 mg after 10 minutes if the target is not reached, then 80 mg every 10 minutes for up to 2 more doses; cumulative maximum 300 mg.

• Or infusion: 1 to 2 mg/minute titrated to response, or a starting infusion of 20 mg/hour doubled every 30 minutes to a maximum 160 mg/hour (practice varies).

• Lower mean arterial pressure by no more than about 25% in the first hour; in pregnancy aim for a pressure under 150/100 mmHg.

• Switch to oral dosing once pressure is controlled; the infusion is rarely needed beyond 24 hours.

Aortic dissection, adult (with or after heart rate control). Infusion 0.5 to 2 mg/minute, aiming for heart rate under 60/min and systolic pressure 100 to 120 mmHg, under specialist direction.

Children, hypertension. Oral 1 to 3 mg/kg daily in 2 divided doses; IV 0.2 to 1 mg/kg bolus (maximum 20 mg) or infusion 0.25 to 3 mg/kg/hour; specialist.

Contraindications. Asthma and severe obstructive airway disease; second or third degree atrioventricular block; severe bradycardia; cardiogenic shock; uncontrolled heart failure; sick sinus syndrome; hypotension; phaeochromocytoma unless alpha blockade is established.

Warnings. Orthostatic hypotension; give IV doses lying down and keep the patient supine for 3 hours. Hepatocellular injury, rarely severe; check liver function with unexplained symptoms. Paradoxical hypertension in phaeochromocytoma. Cocaine toxicity: avoid. Tingling of the scalp. Masks hypoglycaemia.

Adverse effects. Dizziness, postural hypotension, fatigue, headache, nausea, scalp tingling, bradycardia, bronchospasm, hepatic enzyme rise.

Interactions. Halogenated anaesthetics add hypotension. Verapamil and diltiazem: bradycardia and heart block. Nitrates and other antihypertensives add hypotension. Tricyclic antidepressants raise tremor. Cimetidine raises levels. Beta agonists, including salbutamol, are antagonised.

Special groups.

• Pregnancy: first line choice; neonate may have bradycardia, hypotension, hypoglycaemia; monitor the neonate for 24 to 48 hours after exposure near delivery.

• Breastfeeding: small amounts in milk; compatible.

• Older adults: start at 50 to 100 mg twice daily.

• Kidney impairment: no adjustment.

• Liver impairment: reduce dose; avoid in severe disease.

Formulations. Tablets 100 and 200 mg; injection 5 mg/mL (20 mL ampoule, 100 mg).

Administration. IV: give the bolus undiluted over 2 minutes with continuous monitoring. For infusion, dilute to 1 mg/mL in 5% glucose or 0.9% sodium chloride using a syringe pump. Oral doses with food. Incompatible with alkaline solutions such as sodium bicarbonate.

Baseline. Blood pressure supine and standing, heart rate, ECG, liver function, history of asthma.

Monitoring. Blood pressure and heart rate every 5 to 10 minutes during bolus dosing and every 15 minutes during infusion; foetal heart rate monitoring in pregnancy; urine output; liver function with symptoms.

Stopping. Taper over 1 to 2 weeks after long term use.

Common prescribing errors. Using it in a patient with asthma; mixing up IV doses (mg/minute against mg/hour); giving the bolus too quickly; forgetting neonatal monitoring after use near delivery.