What are the dosing parameters for metoprolol (metoprolol succinate ER)?

Metoprolol Succinate ER Dosing Parameters

Formulation and Administration

Metoprolol succinate extended-release (ER) must be dosed once daily, as this is the only formulation proven to reduce mortality in heart failure—metoprolol tartrate (immediate-release) should not be substituted. 1, 2

• The extended-release formulation delivers metoprolol at a near-constant rate over approximately 20 hours, producing even plasma concentrations over 24 hours without marked peaks and troughs 3
• A 100 mg metoprolol ER tablet contains 95 mg of metoprolol succinate and provides equivalent beta-blocking activity to 100 mg metoprolol tartrate 4
• The tablet disintegrates into individual pellets that act as diffusion cells, releasing drug at a relatively constant rate 4

Condition-Specific Dosing

Heart Failure with Reduced Ejection Fraction (HFrEF)

Start at 12.5-25 mg once daily and titrate every 2 weeks to a target dose of 200 mg once daily. 1, 2

• Initial dose selection: Use 12.5 mg for more severe heart failure or 25 mg for mild-moderate heart failure 1, 2
• Titration schedule: 12.5 mg → 25 mg → 50 mg → 100 mg → 200 mg once daily, doubling every 2 weeks if tolerated 1, 2
• Target dose of 200 mg daily achieved a 34% reduction in all-cause mortality in the MERIT-HF trial 1, 5
• If full target cannot be achieved, aim for at least 50% of target dose (100 mg daily minimum) as dose-response relationships exist for mortality benefit 1
• Mean dose achieved in clinical trials was 159 mg daily 1, 2

Hypertension

Start at 50 mg once daily and titrate to 50-200 mg once daily, with a maximum dose of 400 mg daily. 1, 2

• Initial dose: 50 mg once daily 1
• Usual maintenance range: 50-200 mg once daily 2
• Maximum dose: 400 mg once daily 1, 2
• Increase dose gradually every 1-2 weeks if blood pressure control is not achieved 1
• Target blood pressure: <130/80 mmHg 1

Post-Myocardial Infarction

After initial IV therapy in acute MI, start oral metoprolol at 50 mg every 6 hours for 48 hours, then transition to maintenance dosing. 2

• Maintenance dose after MI: 100 mg twice daily of immediate-release formulation 2
• For extended-release formulation, follow heart failure dosing regimen 1

Atrial Fibrillation Rate Control

Start at 50-100 mg once daily and titrate to 50-400 mg once daily based on heart rate response. 1

• Target resting heart rate: 50-60 beats per minute unless limiting side effects occur 1
• Monitor heart rate and blood pressure at each visit during titration 1

Frequent PVCs

Start at 50 mg once daily with a maximum daily dose of 400 mg. 1

• Initial dose: 50 mg once daily 1
• Maximum dose: 400 mg once daily 1

Monitoring Parameters During Titration

Monitor heart rate, blood pressure, clinical status, and signs of congestion at each visit. 1, 2

• Heart rate: Target 50-60 bpm; if <50 bpm with worsening symptoms, halve the dose 1, 6
• Blood pressure: Monitor for symptomatic hypotension (systolic <100 mmHg with symptoms) 1
• Signs of worsening heart failure: Increased dyspnea, weight gain >1.5-2.0 kg over 2 days, peripheral edema 1, 2
• Check blood chemistry 1-2 weeks after initiation and 1-2 weeks after final dose titration 6
• Watch for symptomatic bradycardia, hypotension, fatigue, dizziness, and bronchospasm 1

Absolute Contraindications

Do not initiate metoprolol succinate ER in patients with the following conditions: 1, 2

• Signs of heart failure, low output state, or decompensated heart failure 1, 2
• Current or recent (within 4 weeks) heart failure exacerbation requiring hospitalization 2
• PR interval >0.24 seconds 1, 2
• Second or third-degree heart block without a functioning pacemaker 1, 2
• Active asthma or reactive airways disease 1, 2
• Sinus bradycardia <50 bpm 1
• Systolic blood pressure <100 mmHg with symptoms 1
• Cardiogenic shock or increased risk factors (age >70 years, systolic BP <120 mmHg, heart rate >110 bpm or <60 bpm) 1

Managing Adverse Effects During Titration

Worsening Congestion

First double the diuretic dose; only halve the metoprolol dose if increasing diuretic fails. 1, 6

Symptomatic Bradycardia (HR <50 bpm with symptoms)

Reduce metoprolol dose by 50%. 1, 6

Symptomatic Hypotension

First reduce or eliminate vasodilators (nitrates, calcium channel blockers); second, reduce diuretics if no congestion; third, temporarily reduce metoprolol dose by 50%. 6

Marked Fatigue

Halve the metoprolol dose. 6

Critical Warnings

Never abruptly discontinue metoprolol succinate ER—this can cause severe exacerbation of angina, myocardial infarction, ventricular arrhythmias, and a 2.7-fold increased risk of 1-year mortality. 1

• If discontinuation is necessary, taper by reducing dose by approximately 25-50% every 1-2 weeks under close surveillance 1
• Monitor for signs of worsening heart failure symptoms during tapering 1
• If symptoms worsen during tapering, return to previous dose before attempting more gradual taper 1

Special Population Considerations

Women

Consider starting at 50% of standard doses in women, as metoprolol exposure is 50-80% higher in women than men. 1

• Women may achieve optimal outcomes at 50% of guideline-recommended doses 1
• For elderly women, 15 mg produces similar drug exposure to 50 mg in healthy young men 1

Elderly Patients (>70 years)

Use caution and start at lower end of dosing range, particularly in acute MI settings where age >70 is a risk factor for cardiogenic shock. 1