What is the difference between metoprolol (beta-blocker) succinate and tartrate formulations?

Differences Between Metoprolol Succinate and Tartrate

Metoprolol succinate is an extended-release formulation taken once daily, while metoprolol tartrate is an immediate-release formulation taken multiple times daily, with succinate being preferred in heart failure due to more consistent 24-hour beta-blockade. 1, 2

Pharmacokinetic Differences

• Release Mechanism:

  • Metoprolol Succinate: Extended-release/controlled-release formulation that releases the drug over approximately 20 hours, providing constant plasma concentrations 3, 4
  • Metoprolol Tartrate: Immediate-release formulation with more pronounced peaks and troughs in plasma concentration 4

• Dosing Frequency:

  • Metoprolol Succinate: Once-daily dosing 1, 2
  • Metoprolol Tartrate: Multiple daily dosing (typically twice daily) 1, 2

• Formulation Design:

  • Metoprolol Succinate: Uses a multiple-pellet system where each pellet acts as a diffusion cell releasing the drug at a relatively constant rate 3, 5
  • Metoprolol Tartrate: Available as immediate-release tablets or as sustained-release monolithic matrix tablets 5

Clinical Implications

• Beta-Blockade Duration:

  • Metoprolol Succinate: Provides even beta1-blockade over 24 hours 4
  • Metoprolol Tartrate: Results in more variable beta-blockade with peaks and troughs 4

• Dose Equivalence:

  • 100 mg of metoprolol succinate is equivalent to 100 mg of metoprolol tartrate in terms of total daily beta-blocking activity 3

• Heart Failure Treatment:

  • The American College of Cardiology and American Heart Association specifically recommend metoprolol succinate (not tartrate) for heart failure with reduced ejection fraction 6
  • Metoprolol succinate has been shown to reduce mortality in heart failure patients in large clinical trials 1, 5

Hemodynamic Effects

• Both formulations produce similar hemodynamic effects when comparing equivalent doses 7
• When full doses are administered:
  • Both decrease cardiac index (succinate by 0.5 L/min/m² and tartrate by 0.6 L/min/m²)
  • Both increase systemic vascular resistance
  • Both decrease stroke volume index 7

Practical Considerations

• Initiation:

  • The "start-low, go-slow" approach is recommended for both formulations 1, 6
  • Metoprolol succinate can be initiated at a higher starting dose (25 mg) compared to tartrate (6.25 mg) 7

• FDA Approval Status:

  • Metoprolol succinate is FDA-approved for heart failure treatment 2
  • Metoprolol tartrate is not specifically approved for heart failure 2

Important Clinical Caveat

The COMET trial suggested that carvedilol may be superior to metoprolol tartrate in reducing mortality in heart failure patients, but this cannot be extrapolated to metoprolol succinate due to different pharmacokinetic profiles 2. The Annals of Internal Medicine notes that the lower mortality with carvedilol versus metoprolol tartrate may be related to the short-acting nature of metoprolol tartrate used in that trial 1.

When treating heart failure patients, selective beta-blockers like metoprolol succinate (not tartrate) have demonstrated similar mortality benefits as carvedilol in randomized clinical trials 1.