What is the difference between metoprolol succinate (MS) and metoprolol tartrate (MT) in terms of dosing and patient management?

Metoprolol Succinate vs Metoprolol Tartrate: Key Differences

For heart failure with reduced ejection fraction, use metoprolol succinate extended-release (CR/XL) 12.5-25 mg once daily titrated to a target of 200 mg daily, not metoprolol tartrate, as only the succinate formulation has proven mortality benefit in this population. 1

Critical Distinction in Heart Failure

Metoprolol succinate (extended-release) is the only metoprolol formulation proven to reduce mortality in heart failure patients. 1 The 2005 ACC/AHA guidelines explicitly state that sustained-release metoprolol succinate reduces the risk of death, while immediate-release metoprolol tartrate showed lesser effectiveness in clinical trials. 1 In the COMET trial, carvedilol demonstrated superior mortality reduction compared to metoprolol tartrate, but metoprolol succinate CR/XL showed comparable mortality benefits to carvedilol in the MERIT-HF trial. 1, 2

Formulation and Pharmacokinetic Differences

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

• Dosing frequency: Once daily 1, 3
• Pharmacokinetics: Delivers metoprolol at a near-constant rate over approximately 20 hours, producing even plasma concentrations over 24 hours without marked peaks and troughs 3
• Starting dose for HF: 12.5-25 mg once daily 1
• Target dose for HF: 200 mg once daily 1
• Mean dose achieved in trials: 159 mg daily 1
• Mechanism: Multiple pellet system where each pellet acts as a diffusion cell releasing drug at constant rate 4, 3

Metoprolol Tartrate (Immediate-Release):

• Dosing frequency: Twice or three times daily 5, 6
• Pharmacokinetics: Produces marked peaks and troughs in plasma concentrations 3
• Post-MI dosing: 50 mg every 6 hours for 48 hours, then 100 mg twice daily 5
• Formulation: Immediate-release with shorter duration of action 3

Clinical Application Algorithm

For Heart Failure with Reduced Ejection Fraction:

1. Use only metoprolol succinate CR/XL - metoprolol tartrate is not guideline-recommended for this indication 1
2. Start at 12.5-25 mg once daily 1
3. Titrate to target dose of 200 mg once daily as tolerated 1
4. Ensure patient is stable and not decompensated before initiating 7

For Acute Myocardial Infarction:

1. Early phase: Use metoprolol tartrate IV (three 5 mg boluses at 2-minute intervals) 5
2. Transition: Begin metoprolol tartrate 50 mg every 6 hours orally 15 minutes after last IV dose 5
3. Maintenance: After 48 hours, switch to 100 mg twice daily 5
4. Consider conversion: May transition to metoprolol succinate for long-term management based on heart failure status 1

For Hypertension:

• Either formulation is acceptable 4, 6
• Metoprolol succinate offers once-daily convenience with more consistent 24-hour blood pressure control 4, 3
• Metoprolol tartrate requires twice-daily dosing 6

Dose Equivalence

A 100 mg metoprolol succinate CR/XL tablet contains 95 mg of metoprolol succinate and is considered equivalent to 100 mg metoprolol tartrate in activity. 4 However, this is a pharmacologic equivalence, not a clinical equivalence for all indications - the formulations are not interchangeable for heart failure management. 1

Critical Pitfalls to Avoid

• Never substitute metoprolol tartrate for metoprolol succinate in heart failure patients - only the succinate formulation has mortality benefit 1, 2
• Do not assume milligram-for-milligram equivalence means clinical equivalence - the COMET trial showed metoprolol tartrate (target 50 mg twice daily) was inferior to carvedilol for mortality, while metoprolol succinate at appropriate doses was not 1, 2
• Avoid abrupt discontinuation of either formulation as this can cause rebound tachycardia and symptom worsening 7
• Do not initiate in decompensated heart failure - wait until patient is stabilized 7
• Monitor for hypotension, bradycardia (hold if heart rate <45-50 bpm), and bronchospasm 1, 7

Special Populations

Hepatic Impairment:

• Both formulations require dose reduction and cautious titration due to substantially increased blood levels 5
• Start with low doses regardless of formulation 5

Renal Impairment:

• No dose adjustment required for either formulation 5

Elderly Patients:

• Initiate at low doses with gradual titration for both formulations 5

Tolerability Advantage

Metoprolol succinate's avoidance of high peak plasma concentrations results in fewer adverse effects and improved compliance compared to the immediate-release tartrate formulation. 8, 3 The consistent beta-1 blockade over 24 hours maintains cardioselectivity at doses up to 200 mg daily. 3