Should metoprolol succinate (Extended-Release) be dosed once or twice a day?

Metoprolol Succinate ER Dosing Frequency

Metoprolol succinate extended-release (ER) should be dosed once daily, not twice daily. 1

Critical Distinction Between Formulations

The formulation matters significantly for both efficacy and safety:

• Metoprolol succinate ER is specifically designed as a once-daily formulation that delivers the drug at a near-constant rate over approximately 20 hours, producing even plasma concentrations over 24 hours without marked peaks and troughs. 2, 3

• This once-daily formulation was the specific preparation used in landmark mortality trials (such as MERIT-HF) that demonstrated a 34% reduction in all-cause mortality in heart failure patients. 1, 4

• The extended-release tablet disintegrates into individual pellets, with each pellet acting as a diffusion cell that releases metoprolol at a relatively constant rate over approximately 20 hours, independent of food intake and gastrointestinal pH. 3

Common Pitfall: Dosing Twice Daily

A critical error to avoid: dosing metoprolol succinate ER twice daily is inappropriate and deviates from evidence-based practice. 1

• The American College of Cardiology and American Heart Association guidelines specifically warn that using metoprolol succinate twice daily would be incorrect dosing that was neither the dose nor formulation used in trials showing mortality reduction. 1

• If you need twice-daily dosing, you should use metoprolol tartrate (immediate-release), which requires dosing every 6-12 hours due to its shorter half-life. 1, 5

Standard Dosing Recommendations

For Heart Failure:

• Initial dose: 12.5-25 mg once daily 1, 5
• Target dose: 200 mg once daily 1, 5
• Double the dose every 1-2 weeks if the preceding dose was well tolerated 1

For Hypertension:

• Usual range: 50-400 mg once daily 1
• Maximum dose: 400 mg once daily 5

For Post-Myocardial Infarction:

• After initial stabilization, maintenance dose is 100 mg twice daily - but this refers to metoprolol tartrate, not succinate ER 1

Pharmacokinetic Rationale

• Metoprolol succinate ER maintains consistent beta₁-blockade over 24 hours while preserving cardioselectivity at doses up to 200 mg daily. 2

• Studies comparing twice-daily metoprolol tartrate with once-daily metoprolol succinate showed similar hemodynamic and clinical effects, confirming that once-daily dosing of the ER formulation is sufficient. 6

• The controlled-release design produces less fluctuation in plasma concentrations compared to immediate-release formulations, allowing for convenient once-daily administration. 4

Monitoring During Titration

• Watch for heart failure symptoms, fluid retention, hypotension (systolic BP <100 mmHg), and symptomatic bradycardia (HR <60 bpm with symptoms). 1

• If worsening symptoms occur, increase diuretics or ACE inhibitors before reducing the beta-blocker dose. 1