What is the difference between metoprolol tartrate and metoprolol succinate?

Differences Between Metoprolol Tartrate and Metoprolol Succinate

Metoprolol succinate is an extended-release formulation that provides consistent beta-blockade over 24 hours with once-daily dosing, while metoprolol tartrate is an immediate-release formulation requiring twice-daily dosing to maintain therapeutic effect.

Formulation Differences

• Metoprolol Tartrate:

  • Immediate-release formulation
  • Requires twice-daily dosing (typically 100-200 mg/day in divided doses) 1
  • Rapid absorption with peak plasma concentrations in 1-2 hours
  • Shorter duration of action requiring multiple daily doses
  • Available as immediate-release tablets

• Metoprolol Succinate:

  • Extended-release/controlled-release formulation (CR/XL)
  • Once-daily dosing (typically 50-200 mg once daily) 1
  • Tablet disintegrates into individual pellets that act as diffusion cells releasing drug at a constant rate over approximately 20 hours 2
  • Provides consistent beta-blockade throughout the 24-hour dosing interval 3
  • Less fluctuation in plasma concentrations compared to immediate-release formulation

Dosing Equivalence

• A 100 mg metoprolol succinate tablet contains 95 mg of metoprolol succinate and is considered therapeutically equivalent to 100 mg of metoprolol tartrate 2
• When switching between formulations, the total daily dose remains the same, but the frequency changes:
  • 50 mg metoprolol tartrate twice daily ≈ 100 mg metoprolol succinate once daily
  • 100 mg metoprolol tartrate twice daily ≈ 200 mg metoprolol succinate once daily

Clinical Applications and Evidence

Heart Failure

• Metoprolol Succinate is preferred for heart failure with reduced ejection fraction (HFrEF):

  • Specifically studied in MERIT-HF trial showing 34% reduction in all-cause mortality 3
  • Listed in guidelines as one of three beta-blockers proven to reduce mortality in HFrEF 1
  • Target dose: 200 mg once daily 1

• Metoprolol Tartrate:

  • Not recommended for heart failure based on the COMET trial, which showed inferior outcomes compared to carvedilol 4
  • Was not the formulation used in the major mortality trials for heart failure 1

Hypertension

• Both formulations are effective for hypertension 1
• Metoprolol succinate offers the advantage of once-daily dosing and more consistent blood pressure control 2

Pharmacokinetic Differences

• Metoprolol Tartrate:

  • Rapid absorption and elimination
  • Half-life of approximately 3-7 hours
  • More pronounced peak and trough effects

• Metoprolol Succinate:

  • Controlled release over approximately 20 hours 2
  • More consistent plasma concentrations throughout the day
  • Reduced peak-to-trough ratio
  • May allow for higher total daily doses with fewer side effects

Hemodynamic Effects

• Both formulations produce similar overall hemodynamic effects when given at equivalent doses 5
• During chronic therapy, both formulations show similar effects on:
  • Cardiac index
  • Systemic vascular resistance
  • Stroke volume index 5

Clinical Advantages of Metoprolol Succinate

• Better patient adherence with once-daily dosing
• More consistent beta-blockade throughout 24 hours
• Fewer peak-related side effects
• Preferred in heart failure based on mortality evidence 1
• May be initiated at higher starting doses compared to tartrate formulation (25 mg vs. 6.25 mg) 5

Common Pitfalls and Caveats

• Do not substitute formulations without dose adjustment: When switching between formulations, maintain the same total daily dose but adjust the frequency
• Not interchangeable in heart failure: Only metoprolol succinate has proven mortality benefit in HFrEF
• Abrupt discontinuation: Both formulations should not be stopped abruptly due to risk of rebound hypertension or worsening angina 1
• Dosing confusion: Metoprolol succinate should be taken once daily, while tartrate requires twice-daily dosing
• Tablet integrity: Metoprolol succinate extended-release tablets should be swallowed whole, not crushed or chewed 6

When selecting between these formulations, consider the specific indication (particularly for heart failure where succinate is preferred), patient adherence factors, and the desired consistency of beta-blockade over the dosing interval.