Metoprolol Succinate vs. Tartrate: Critical Formulation Differences
Metoprolol succinate is the only metoprolol formulation proven to reduce mortality in heart failure with reduced ejection fraction and should never be substituted with metoprolol tartrate in this population. 1
Formulation and Pharmacokinetics
Metoprolol succinate is an extended-release formulation that provides:
- Once-daily dosing with consistent beta-1 blockade throughout the entire 24-hour period 2, 1
- Steady plasma concentrations without marked peaks and troughs 1, 3, 4
- Drug release over approximately 20 hours through a controlled-release tablet that disintegrates into individual pellets 5, 4
- Equivalent dosing: 95 mg metoprolol succinate = 100 mg metoprolol tartrate 5
Metoprolol tartrate is an immediate-release formulation that:
- Requires twice-daily dosing (every 6-12 hours) due to marked peaks and troughs in plasma concentrations 2, 1, 4
- Produces less consistent beta-1 blockade over 24 hours 1, 4
- Can be given intravenously for acute situations (5 mg IV every 5 minutes up to 3 doses) 2
Clinical Efficacy: Where the Formulations Diverge
Heart Failure with Reduced Ejection Fraction (HFrEF)
Metoprolol succinate is the ONLY acceptable formulation for HFrEF:
- Demonstrated 34% relative risk reduction in all-cause mortality in the MERIT-HF trial 1, 3
- Reduced sudden death by 41% and combined mortality plus hospitalization by 19% 3
- Specifically recommended by ACC/AHA guidelines for patients with LVEF ≤40% 1
- Target dose: 200 mg once daily (mean achieved dose in trials: 159 mg daily) 1
- Initial dose: 12.5-25 mg once daily, titrated gradually 1
Metoprolol tartrate is NOT proven for mortality reduction in heart failure:
- Showed inferior outcomes compared to carvedilol in the COMET trial 1
- Critical pitfall: Never substitute tartrate for succinate in heart failure patients 1
Post-Myocardial Infarction
Both formulations can be used acutely:
- Oral beta blockers should be initiated within the first 24 hours in STEMI patients without contraindications 2
- Metoprolol tartrate: 25-50 mg every 6-12 hours orally, then transition over 2-3 days to twice-daily tartrate OR daily succinate 2
- Titrate to target daily dose of 200 mg as tolerated 2
- Metoprolol succinate is preferred for long-term therapy when left ventricular dysfunction is present 1
Hypertension
Both formulations are effective, with succinate offering convenience:
- Metoprolol tartrate: 100-200 mg total daily dose, divided twice daily 2
- Metoprolol succinate: 50-200 mg once daily 2
- Neither is recommended as first-line for hypertension unless the patient has ischemic heart disease or heart failure 2
Rate Control (Atrial Fibrillation, Supraventricular Tachycardia)
Both formulations are acceptable:
- Metoprolol succinate offers once-daily convenience 1
- IV metoprolol tartrate (2.5-5 mg bolus over 2 minutes, up to 3 doses) for acute rate control 1
Dosing Algorithm by Clinical Scenario
For HFrEF (LVEF ≤40%):
- Use ONLY metoprolol succinate 1
- Start: 12.5-25 mg once daily 1
- Target: 200 mg once daily 1
- Titrate gradually in stable patients on ACE inhibitors and diuretics 3
For post-MI without heart failure:
- Start metoprolol tartrate 25-50 mg every 6-12 hours 2
- Transition to metoprolol succinate for long-term convenience 2, 1
- Target: 200 mg total daily dose 2
For hypertension:
- Either formulation acceptable 2
- Metoprolol succinate 50-200 mg once daily preferred for compliance 2
- Metoprolol tartrate 100-200 mg divided twice daily if succinate unavailable 2
Contraindications and Cautions (Apply to Both Formulations)
Avoid in: 2
- Signs of heart failure (during acute initiation)
- Low output state or increased risk of cardiogenic shock
- PR interval >0.24 seconds, second- or third-degree heart block
- Active asthma or reactive airways disease
- Systolic BP <90 mmHg
Avoid abrupt cessation of either formulation to prevent rebound hypertension and ischemia 2