What are the differences between metoprolol succinate (extended‑release) and metoprolol tartrate (immediate‑release) regarding dosing, clinical indications, and conversion?

Metoprolol Succinate versus Tartrate: Key Differences

Metoprolol succinate (extended-release) is the only formulation with proven mortality benefit in heart failure and should be dosed once daily at a target of 200 mg, while metoprolol tartrate (immediate-release) has never demonstrated mortality reduction in heart failure trials and is reserved for acute situations requiring rapid titration. 1

Formulation Differences

Pharmacokinetic Profile

• Metoprolol succinate delivers the drug at a near-constant rate over approximately 20 hours, producing even plasma concentrations over 24 hours without marked peaks and troughs, maintaining consistent β1-blockade while preserving cardioselectivity at doses up to 200 mg daily 2

• Metoprolol tartrate produces characteristic peak-and-trough plasma concentration patterns with higher peak levels and lower trough concentrations compared to the extended-release formulation 2, 3

• The extended-release formulation results in 3- to 4-fold higher trough concentrations, 8–9 hour longer mean residence times, and approximately 20% lower relative bioavailability compared to immediate-release tablets 3

Food and pH Independence

• Metoprolol succinate absorption remains independent of food intake and gastrointestinal pH, ensuring predictable drug delivery 2

Clinical Indications by Formulation

Metoprolol Succinate (Extended-Release) – Evidence-Based Uses

• Heart failure with reduced ejection fraction: Initial dose 12.5–25 mg once daily, titrated every 2 weeks to target dose of 200 mg once daily 4, 5

  • This is the only formulation with proven mortality benefit in heart failure (34% reduction in all-cause mortality in MERIT-HF trial) 1

• Hypertension: Initial dose 50 mg once daily, maximum 400 mg once daily, titrated every 1–2 weeks 4

• Atrial fibrillation rate control: 50–400 mg once daily, targeting resting heart rate 50–80 bpm 4

• Post-myocardial infarction secondary prevention: Target dose 200 mg once daily for mortality reduction 1, 4

Metoprolol Tartrate (Immediate-Release) – Acute/Titration Uses

• Acute situations requiring rapid dose adjustment: Initial 25–50 mg twice daily 4

  • Used when transitioning from IV to oral therapy (start 15 minutes after last IV dose at 25–50 mg every 6 hours for 48 hours) 4

• Hypertension (when extended-release unavailable): 25–50 mg twice daily, maximum 200 mg twice daily 4

• Atrial fibrillation rate control: 25–100 mg twice daily 4

• Critical limitation: Metoprolol tartrate has never demonstrated mortality benefit in heart failure trials and was merely the comparator (not the active treatment) in the COMET trial 1

Dosing Conversion Between Formulations

No Direct Milligram-for-Milligram Conversion

• There is no established dose-equivalence algorithm between metoprolol tartrate and metoprolol succinate 1

• When switching formulations, the general principle is that total daily doses are approximately equivalent (e.g., tartrate 50 mg twice daily ≈ succinate 100 mg once daily), but this is based on pharmacokinetic modeling rather than clinical trial evidence 4

Switching from Tartrate to Succinate

• For heart failure patients on tartrate: Switch to metoprolol succinate 200 mg once daily (the evidence-based formulation) rather than attempting dose conversion 1

• Start succinate at 12.5–25 mg once daily and titrate up every 2 weeks regardless of previous tartrate dose, as tartrate is not evidence-based for heart failure 1, 4

Switching from Succinate to Tartrate

• This switch is not recommended except in acute situations requiring rapid titration (e.g., hemodynamic instability) 4

• If necessary for acute management, start tartrate at 25–50 mg every 6 hours and transition back to succinate once stable 4

Critical Contraindications (Both Formulations)

• Signs of heart failure, low output state, or decompensated heart failure 4

• PR interval >0.24 seconds, second- or third-degree heart block without functioning pacemaker 4

• Active asthma or reactive airways disease 4

• Systolic BP <100 mmHg with symptoms 4

• Symptomatic bradycardia (heart rate <50–60 bpm with dizziness or syncope) 4

Common Pitfalls to Avoid

• Never substitute metoprolol tartrate for metoprolol succinate in heart failure management—only succinate has proven mortality benefit 1

• Never abruptly discontinue either formulation—sudden withdrawal precipitates angina, myocardial infarction, ventricular arrhythmias, and a 2.7-fold increased risk of 1-year mortality 1, 4

• Do not use immediate-release tartrate for chronic heart failure maintenance therapy—it lacks the evidence base and consistent β-blockade profile needed for mortality reduction 1, 2

• When tapering is required, reduce the dose by 25–50% every 1–2 weeks while monitoring for worsening heart failure symptoms, rebound hypertension, or tachycardia 4

Monitoring Parameters (Both Formulations)

• Blood pressure and heart rate at each visit, targeting resting heart rate 50–60 bpm unless limiting side effects occur 4

• Signs of worsening heart failure (dyspnea, edema, weight gain) 4

• Symptomatic hypotension (systolic BP <100 mmHg with dizziness or lightheadedness) 4

• Symptomatic bradycardia (heart rate <60 bpm with symptoms) 4

• Bronchospasm, particularly in patients with any history of reactive airway disease 4