Metoprolol Succinate Should Not Be Given Twice Daily
Metoprolol succinate (extended-release) is specifically formulated for once-daily administration and should not be dosed twice daily. 1, 2 The extended-release formulation is designed to deliver metoprolol at a near-constant rate over approximately 20 hours, providing consistent beta-1 blockade throughout a 24-hour period with a single daily dose. 3
Critical Formulation Distinction
Only metoprolol succinate extended-release has proven mortality reduction in heart failure, and it must be dosed once daily as studied in clinical trials. 1, 2 The MERIT-HF trial, which demonstrated a 34% reduction in all-cause mortality, used metoprolol succinate dosed once daily at target doses of 200 mg daily. 1, 2
- Metoprolol tartrate (immediate-release) is the formulation given twice daily at doses of 25-100 mg twice daily 1, 4
- Metoprolol succinate (extended-release/CR/XL) is given once daily at doses of 12.5-200 mg once daily 1, 2
- These are not interchangeable formulations—metoprolol tartrate has not demonstrated mortality reduction in heart failure 2
Pharmacokinetic Rationale
The extended-release formulation disintegrates into individual pellets that act as diffusion cells, releasing drug at a relatively constant rate over 20 hours. 5, 3 This produces:
- Even plasma concentrations over 24 hours without marked peaks and troughs 3
- Consistent beta-1 blockade throughout the day while maintaining cardioselectivity at doses up to 200 mg daily 3
- More pronounced and even beta-1 blockade compared to immediate-release formulations 3
Evidence-Based Dosing Schedules
For heart failure with reduced ejection fraction:
- Start metoprolol succinate at 12.5-25 mg once daily 1, 2
- Titrate by doubling the dose every 2 weeks as tolerated 1, 2
- Target dose: 200 mg once daily 1, 2
For hypertension:
- Start metoprolol succinate at 50 mg once daily 2, 4
- Titrate to 50-400 mg once daily based on blood pressure response 2
Common Pitfall to Avoid
Never split the once-daily metoprolol succinate dose into twice-daily administration. 1, 2 This defeats the purpose of the extended-release formulation and has not been studied in clinical trials. If twice-daily dosing is needed for any clinical reason, switch to metoprolol tartrate (immediate-release) at appropriate divided doses, though this formulation lacks mortality benefit in heart failure. 2
The hemodynamic effects of metoprolol tartrate twice daily and metoprolol succinate once daily are similar when given at equivalent total daily doses, but the once-daily succinate formulation offers the advantage of consistent 24-hour coverage and improved adherence. 6