Metoprolol

Why this drug is interesting

Metoprolol matters in UK emergency practice largely because of what it is not: it is not oral-only. With no intravenous diltiazem available in the UK and intravenous verapamil carrying significant negative inotropy, metoprolol is the intravenous agent most departments will actually use for acute rate control in a tachyarrhythmia.

It is also a good example of a label that has not kept up with a trial. The SmPC still asserts that early intravenous administration in acute myocardial infarction reduces infarct size, ventricular fibrillation and mortality.¹ COMMIT, which randomised nearly 46,000 patients, found that early intravenous then oral metoprolol did not reduce the composite of death, reinfarction or cardiac arrest, and increased cardiogenic shock.⁴

Pharmacology

Mechanism

Metoprolol is a competitive antagonist at beta-1 adrenoceptors, with relative selectivity over beta-2. Blocking cardiac beta-1 receptors reduces heart rate, contractility, AV nodal conduction velocity and myocardial oxygen demand, and suppresses renin release.

Kinetics

Onset after IV

Within minutes; peak effect around 20 minutes

Half-life

3–4 hours

Metabolism

Hepatic, principally CYP2D6 — poor metabolisers achieve substantially higher concentrations

Lipophilicity

Lipophilic — crosses the blood-brain barrier, contributing to fatigue, vivid dreams and nightmares

Formulations

Tartrate (immediate-release, and the injection) and succinate (modified-release) — not interchangeable milligram for milligram

The relatively short half-life is an advantage in an acute setting: if a titrated dose is poorly tolerated, the effect is measured in hours rather than the days that amiodarone would impose.

Indications and dosing

The injection is licensed for control of tachyarrhythmias, especially supraventricular tachyarrhythmias, with the SmPC adding that the electrocardiogram should be monitored during treatment.¹

Intravenous dosing for cardiac arrhythmias

Initially up to 5 mg injected intravenously at a rate of 1–2 mg per minute. The injection can be repeated at 5 minute intervals until a satisfactory response has been obtained. A total dose of 10–15 mg generally proves sufficient.

Betaloc 1 mg/ml Solution for Injection, SmPC section 4.2¹

• The ampoule is 5 mg in 5 mL (1 mg/mL), so the initial dose is one ampoule given over 2.5–5 minutes
• Caution where systolic blood pressure is below 100 mmHg
• Titrate to ventricular rate and tolerance, not to a fixed total

Rate control in atrial fibrillation

The RCUK 2025 adult tachyarrhythmia algorithm places beta-blockade first among the rate-control options and — importantly — keeps it available across the range of ventricular function:³

The COMMIT problem

The SmPC states that early intravenous administration in acute myocardial infarction reduces infarct size, the incidence of ventricular fibrillation and mortality, and may reduce opiate requirements.¹ That reflects pre-reperfusion-era evidence.

COMMIT/CCS-2 randomised 45,852 patients with acute myocardial infarction to early intravenous then oral metoprolol or placebo.⁴ Its findings:

• No reduction in the composite of death, reinfarction or cardiac arrest
• Reduced reinfarction and ventricular fibrillation
• Increased cardiogenic shock, with the excess concentrated in haemodynamically compromised patients
• Net benefit in low-risk patients; net harm in those with poorer prognostic signs

This is the same pattern seen with ketamine's intracranial pressure contraindication and flecainide's CAST legacy: a label or a doctrine that has been overtaken, in one direction or the other, by a large trial. Teaching the divergence explicitly is more useful than teaching either half alone.

Contraindications, interactions and adverse effects

Contraindications

• Hypersensitivity to metoprolol or excipients
• Hypotension
• Second- or third-degree AV block
• Unstable, decompensated cardiac failure
• Patients on continuous or intermittent inotropic beta-agonist therapy
• Bradycardia below 45 beats per minute
• Sick sinus syndrome without a pacemaker
• Cardiogenic shock
• Severe peripheral arterial circulatory disorders
• Untreated phaeochromocytoma
• Metabolic acidosis

Adverse effects

• Bradycardia, AV block, hypotension
• Precipitation or worsening of heart failure
• Bronchospasm — dose-related, cardioselectivity being relative
• Fatigue, dizziness, cold extremities
• Vivid dreams, nightmares and sleep disturbance — a consequence of lipophilicity and CNS penetration
• Masking of hypoglycaemic warning symptoms in diabetes — particularly the adrenergic ones
• Rarely, bronchospasm-driven deterioration in undiagnosed obstructive airways disease

Interactions

• Verapamil and diltiazem — as above
• CYP2D6 inhibitors — fluoxetine, paroxetine, bupropion, terbinafine — raise metoprolol concentrations
• Other rate-limiting agents including digoxin, amiodarone and ivabradine — additive bradycardia
• Clonidine — risk of rebound hypertension if clonidine is withdrawn while beta-blockade continues

Critical appraisal

1. The intravenous rate-control evidence is reasonable but does not clearly favour beta-blockade over calcium channel blockade. Systematic reviews comparing intravenous diltiazem with intravenous metoprolol in AF with rapid ventricular response have tended to favour diltiazem on speed and success of rate control — a comparison UK clinicians largely cannot act on, since there is no intravenous diltiazem here.
2. COMMIT is the single most important trial for this drug and its message is nuanced rather than prohibitive: beta-blockade in ACS is beneficial, but the timing and the route matter, and the harm falls on the haemodynamically compromised. A summary that reduces it to "don't give beta-blockers in MI" is as wrong as the SmPC's wording.
3. Formulation confusion is a genuine safety issue. Metoprolol tartrate and succinate are not interchangeable milligram for milligram, and the UK's intravenous and immediate-release oral products are tartrate. Conversions at admission and discharge deserve care.
4. The evidence base for beta-blockade in AF rate control is largely extrapolated from chronic management, not from ED cohorts, and the ED-relevant question — what actually improves symptoms and disposition for the patient in front of you — is less well studied than the mechanism suggests.
5. Cardioselectivity is routinely over-trusted. In a patient with significant asthma, the safest answer is often a different drug class rather than a more selective beta-blocker.

References

1. 1
   Betaloc 1 mg/ml Solution for Injection — Summary of Product Characteristics. electronic Medicines Compendium. Sections 4.1–4.3. Verified 20 Aug 2026.
2. 2
   Metoprolol tartrate — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk
3. 3
   Resuscitation Council UK. Adult tachyarrhythmia algorithm, 2025. resus.org.uk — mirrored at lifesupport.resusdoc.uk.
4. 4
   COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005;366(9497):1622–32. PubMed
5. 5
   Verapamil 2.5 mg/ml Solution for injection — Summary of Product Characteristics. electronic Medicines Compendium. Source of the reciprocal contraindication.
6. 6
   Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J 2023;44(38):3720–3826.