What is the difference between metoprolol succinate and metoprolol tartrate?

Metoprolol Succinate vs. Tartrate: Key Differences

Metoprolol succinate is the extended-release formulation proven to reduce mortality in heart failure, while metoprolol tartrate is the immediate-release form that has NOT demonstrated mortality benefit in heart failure and should not be used for this indication. 1

Formulation and Pharmacokinetics

Metoprolol Succinate (Extended-Release/CR/XL):

• Controlled-release tablet using multiple pellet technology that delivers metoprolol at a near-constant rate over approximately 20 hours 2, 3
• Produces even plasma concentrations over 24 hours without marked peaks and troughs 4, 3
• Dosed once daily (QD) 1
• Provides consistent beta-1 blockade throughout the entire 24-hour dosing interval 2, 4, 3
• Independent of food intake and gastrointestinal pH 3

Metoprolol Tartrate (Immediate-Release):

• Immediate-release formulation with rapid absorption 5
• Produces marked peaks and troughs in plasma concentrations 4, 3
• Requires twice-daily (BID) dosing 1
• Less consistent beta-1 blockade over 24 hours 3

Clinical Efficacy: The Critical Distinction

Heart Failure with Reduced Ejection Fraction (HFrEF):

• Only metoprolol succinate (CR/XL) is recommended for mortality reduction in heart failure 1
• Metoprolol succinate demonstrated 34% relative risk reduction in all-cause mortality in the MERIT-HF trial 4
• Metoprolol succinate reduced sudden death by 41% and the combined endpoint of mortality plus hospitalizations by 19% 4
• Metoprolol tartrate showed inferior outcomes compared to carvedilol in the COMET trial and is NOT the formulation proven to reduce mortality 1, 6
• The dose and formulation matter: metoprolol tartrate at 50 mg BID (used in COMET) was neither the dose nor formulation used in trials showing mortality benefit 1

Post-Myocardial Infarction:

• Both formulations can be used, though metoprolol tartrate is more commonly studied in the acute setting 1
• For long-term therapy post-MI with left ventricular dysfunction, metoprolol succinate is preferred 1

Hypertension and Supraventricular Tachycardia:

• Both formulations are effective 1
• Metoprolol succinate offers convenience of once-daily dosing 1

Dosing Recommendations

Metoprolol Succinate for Heart Failure:

• Initial dose: 12.5-25 mg once daily 1
• Target dose: 200 mg once daily 1
• Mean dose achieved in clinical trials: 159 mg once daily 1

Metoprolol Tartrate (when appropriate):

• Hypertension: 25-50 mg every 6-12 hours, titrate to 200 mg daily total dose 1
• Post-MI acute setting: IV 5 mg every 5 minutes up to 3 doses, then oral 1

Tolerability Profile

• Metoprolol succinate's avoidance of high peak plasma concentrations is associated with lesser degree of adverse effects and may improve patient compliance 2
• Both formulations produce similar hemodynamic effects acutely and chronically, with comparable adverse hemodynamic responses upon drug readministration 5
• Discontinuation rates due to adverse events are similar between metoprolol succinate and placebo (9.8% vs 11.7%) 4

Critical Clinical Pitfall

The most important caveat: Do not substitute metoprolol tartrate for metoprolol succinate in heart failure patients. Although both contain the same active drug (metoprolol), the formulation difference translates to different clinical outcomes in heart failure. 1 The immediate-release tartrate formulation, even at commonly prescribed doses, has not demonstrated the mortality benefit seen with the extended-release succinate formulation. 1, 6