Metoprolol

Metoprolol is a lipid soluble, beta 1 selective blocker given as immediate release tartrate or once daily succinate. It is used in hypertension, angina, chronic heart failure with reduced ejection fraction (succinate only), rate control in atrial fibrillation, acute myocardial infarction and migraine prophylaxis. Two salts with different release profiles are the main source of dosing errors.

Classification. Cardioselective beta 1 adrenergic blocker; no intrinsic sympathomimetic activity.

Mechanism. Blocks beta 1 receptors, lowering heart rate, contractility, atrioventricular conduction and renin release. Selectivity is lost at high doses.

Pharmacodynamics. Tartrate acts for 6 to 12 hours; succinate gives 24 hour control. Reduces mortality in heart failure with reduced ejection fraction and after myocardial infarction.

Pharmacokinetics. Extensive first pass metabolism; oral bioavailability about 50%. Half life 3 to 7 hours. Metabolised by CYP2D6; poor metabolisers have several fold higher exposure. Metabolites are excreted in urine.

Hypertension, adult.

• Tartrate: 50 to 100 mg daily in one or two doses, increased weekly; usual 100 to 200 mg daily; maximum 400 mg daily.

• Succinate: 25 to 100 mg once daily, increased weekly; maximum 400 mg daily.

Angina, adult. Tartrate 50 mg two or three times daily, to a maximum of 400 mg daily; or succinate 100 to 200 mg once daily.

Heart failure with reduced ejection fraction, adult (succinate only).

• Start 12.5 to 25 mg once daily in stable patients.

• Double the dose every 2 weeks as tolerated.

• Target 200 mg once daily; maximum 200 mg daily.

• Do not start in acute decompensation; start when euvolaemic.

Atrial fibrillation rate control, adult. Oral 25 to 100 mg twice daily. IV 2.5 to 5 mg over 2 minutes, repeated every 5 minutes to a maximum of 15 mg, with continuous ECG and blood pressure.

Acute myocardial infarction, adult. Early IV use is limited to selected stable patients: 5 mg IV over 2 minutes, repeated every 2 minutes to 3 doses (15 mg), then 50 mg orally every 6 hours for 48 hours, then 100 mg twice daily. Oral therapy within 24 hours is usual for most patients.

Migraine prophylaxis, adult. 100 to 200 mg daily in one or two doses.

Children, hypertension. 1 mg/kg once daily (maximum 50 mg initially), increased as needed to a maximum 2 mg/kg daily or 200 mg daily. Specialist.

Contraindications. Second or third degree atrioventricular block; sick sinus syndrome; severe bradycardia (under 45 to 50/min); cardiogenic shock; severe peripheral arterial disease; decompensated heart failure; untreated phaeochromocytoma.

Warnings. Abrupt withdrawal can precipitate angina, myocardial infarction and arrhythmia; taper over 1 to 2 weeks. Masks tachycardia of hypoglycaemia and thyrotoxicosis. Caution in asthma and chronic obstructive pulmonary disease (use the lowest dose of a selective agent only if essential). Worsens claudication and Raynaud phenomenon.

Adverse effects. Bradycardia, fatigue, dizziness, cold extremities, sleep disturbance, depression, bronchospasm, heart failure in susceptible patients, erectile dysfunction.

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

Special groups.

• Pregnancy: used when needed; risk of foetal growth restriction, neonatal bradycardia and hypoglycaemia; monitor.

• Breastfeeding: low milk levels; acceptable with infant observation.

• Older adults: start at the lower dose.

• Kidney impairment: no adjustment.

• Liver impairment: reduce dose; bioavailability rises.

Formulations. Tartrate 25, 50, 100 mg tablets; succinate extended release 25, 50, 100, 200 mg; injection 1 mg/mL.

Administration. Take with or just after food. Succinate tablets may be halved at the score but must not be crushed or chewed. Do not interchange tartrate and succinate milligram for milligram without adjusting the schedule (total daily dose is the same; the dosing frequency differs).

Baseline. Pulse, blood pressure, ECG, airway history, glucose, liver function.

Monitoring. Resting heart rate (reduce the dose for rate under 50/min), blood pressure, heart failure symptoms and weight, glucose in diabetes.

Stopping. Taper over 1 to 2 weeks.

Common prescribing errors. Using tartrate in heart failure; starting beta blocker in decompensated heart failure; stopping abruptly; ignoring CYP2D6 inhibitors.