Metoprolol Succinate Extended-Release Should NOT Be Dosed Twice Daily
Metoprolol succinate extended-release (ER) is specifically formulated for once-daily administration only, and prescribing 100mg twice daily represents incorrect dosing that deviates from evidence-based practice and FDA-approved labeling. 1, 2, 3
Critical Formulation Distinction
Only metoprolol succinate extended-release has proven mortality reduction in heart failure, and this benefit was achieved with once-daily dosing at a target of 200mg daily—not twice-daily administration. 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. 4, 5
- This controlled-release design provides consistent beta-1 blockade throughout the entire 24-hour dosing interval with once-daily administration. 4, 5
- The MERIT-HF trial, which demonstrated a 34% reduction in all-cause mortality, used metoprolol succinate ER dosed once daily at a target of 200mg. 1, 5
Why Twice-Daily Dosing Is Inappropriate
The American College of Cardiology and American Heart Association guidelines specifically warn that dosing metoprolol succinate twice daily is inappropriate and deviates from evidence-based practice. 1
- Metoprolol tartrate (immediate-release) requires twice-daily dosing due to its shorter half-life, but this formulation has NOT demonstrated mortality reduction in heart failure. 1, 2
- The extended-release pellet system in metoprolol succinate ER is engineered to release drug over 20 hours, making twice-daily dosing pharmacologically unnecessary and potentially leading to excessive drug exposure. 4, 6
- Prescribing 100mg twice daily (200mg total daily) would be the correct total daily dose, but splitting it defeats the purpose of the extended-release formulation. 1, 2
Correct Dosing Protocol
For heart failure with reduced ejection fraction, start metoprolol succinate ER at 12.5-25mg once daily and titrate every 2 weeks to a target of 200mg once daily. 1, 2
- Titration schedule: 12.5mg → 25mg → 50mg → 100mg → 200mg once daily, doubling the dose every 2 weeks if tolerated. 1, 7
- If the full target dose cannot be achieved, aim for at least 50% of target (100mg daily minimum) to maintain mortality benefit. 1, 2
- For hypertension, the usual dose range is 50-400mg once daily (maximum 400mg daily). 2, 7
Common Prescribing Pitfall
Never confuse metoprolol succinate ER with metoprolol tartrate—they are NOT interchangeable and have different dosing frequencies. 1, 2
- Metoprolol tartrate: 25-100mg twice daily (immediate-release). 1, 7
- Metoprolol succinate ER: 12.5-200mg once daily (extended-release). 1, 2
- The FDA label for metoprolol tartrate specifies dosing every 6-12 hours for acute MI, transitioning to twice-daily maintenance dosing—but this applies only to the immediate-release formulation. 3
Bottom Line
If the patient needs 200mg total daily dose of metoprolol succinate ER, prescribe 200mg once daily, not 100mg twice daily. 1, 2 The twice-daily regimen would only be appropriate if switching to metoprolol tartrate immediate-release, which lacks the mortality benefit proven with the extended-release formulation. 1, 2