What is the recommended dosage and usage of Metoprolol (beta-blocker) for patients with hypertension or heart failure?

Metoprolol Dosing for Hypertension and Heart Failure

Heart Failure with Reduced Ejection Fraction (HFrEF)

Use metoprolol succinate extended-release (CR/XL) exclusively for heart failure—metoprolol tartrate (immediate-release) has not demonstrated mortality reduction and should never be used for this indication. 1, 2

Starting Dose and Titration

• Initial dose: 12.5-25 mg once daily, depending on heart failure severity 1, 2
• Titration schedule: Double the dose every 2 weeks as tolerated 1, 2
• Progression: 12.5 mg → 25 mg → 50 mg → 100 mg → 200 mg once daily 1, 2
• Target dose: 200 mg once daily 1, 2

Mortality Benefits

• Metoprolol CR/XL achieved a 34% reduction in all-cause mortality in the MERIT-HF trial 1, 3
• 38% decrease in cardiovascular mortality 1
• 41% decrease in sudden death 1
• 49% decrease in death from progressive heart failure 1
• 35% reduction in heart failure hospitalization 1
• Number needed to treat: 27 patients for 1 year to prevent 1 death 1

Achieving Target Doses

• At the conclusion of MERIT-HF, 64% of patients reached the target dose of 200 mg daily 1
• If target dose cannot be tolerated, aim for at least 50% of target (100 mg daily minimum) to maintain mortality benefit 1, 2
• Some beta-blocker is better than no beta-blocker—even lower doses provide benefit 1

Monitoring During Titration

• Heart rate: Target resting heart rate 50-60 bpm unless limiting side effects occur 2
• Blood pressure: Monitor at each visit; target <130/80 mmHg 1
• Clinical status: Watch for signs of congestion, weight gain, dyspnea, peripheral edema 1, 2
• Daily weights: Patients should weigh themselves daily and increase diuretic if weight increases by 1.5-2.0 kg over 2 days 1
• Blood chemistry: Check 12 weeks after initiation and 12 weeks after final dose titration 1

Managing Adverse Effects During Titration

For worsening congestion:

• First: Double the diuretic dose 1
• Second: Halve the metoprolol dose only if increasing diuretic fails 1, 2

For marked fatigue or bradycardia:

• Halve the metoprolol dose 1

For heart rate <50 bpm with worsening symptoms:

• Halve the dose or stop if severe deterioration 1, 2

For symptomatic hypotension:

• First: Reduce or eliminate vasodilators (nitrates, calcium channel blockers) 1
• Second: Reduce diuretics if no congestion present 1
• Third: Only then reduce metoprolol dose by 50% 1

Critical Contraindications

• Current or recent (within 4 weeks) heart failure exacerbation requiring hospitalization 1, 2, 4
• Signs of low output state or cardiogenic shock 1, 2, 4
• PR interval >0.24 seconds 1, 2, 4
• Second or third-degree heart block without pacemaker 1, 2, 4
• Active asthma or reactive airways disease 1, 2, 4
• Systolic BP <120 mmHg with risk factors for shock 1, 2
• Heart rate >110 bpm or <60 bpm in acute settings 1, 2

Special Population: Women

• Women may achieve optimal outcomes at 50% of guideline-recommended doses 2
• Metoprolol exposure is 50-80% higher in women than men 2
• Consider starting at 12.5 mg once daily in women and titrating more cautiously 2
• In elderly women, 25 mg produces similar drug exposure to 100 mg in healthy young men 2

Hypertension

Beta-blockers are not recommended as first-line agents for hypertension unless the patient has ischemic heart disease or heart failure. 1

Dosing Options

Metoprolol tartrate (immediate-release):

• Initial dose: 25-50 mg twice daily 1, 2
• Usual dose: 100-200 mg daily in divided doses 1
• Maximum dose: 200 mg twice daily 2

Metoprolol succinate (extended-release):

• Initial dose: 50-200 mg once daily 2
• Maximum dose: 400 mg daily 2

Titration for Hypertension

• Increase dose gradually every 1-2 weeks if blood pressure control not achieved 2
• Target blood pressure: <130/80 mmHg for most patients 1
• Target resting heart rate: 50-60 bpm unless limiting side effects occur 2

Evidence for Efficacy

• Metoprolol 50 mg once daily (CR formulation) produced significant reductions in blood pressure in mild hypertension 5
• In elderly patients (mean age 68 years), metoprolol CR 50 mg daily significantly reduced diastolic pressure by 22 mmHg supine and standing 5
• Metoprolol CR 100 mg once daily was effective in mild to moderate hypertension, with 83% of patients achieving diastolic BP <95 mmHg after 12 weeks 6

Post-Myocardial Infarction

Early Treatment (Acute Phase)

Intravenous administration:

• Dose: Three bolus injections of 5 mg each, given at approximately 2-minute intervals 2, 4
• Maximum total IV dose: 15 mg 2, 4
• Setting: Must be administered in coronary care or similar unit with intensive monitoring 4
• Monitoring: Continuous blood pressure, heart rate, and ECG monitoring during IV administration 2, 4

Transition to oral therapy:

• For patients tolerating full IV dose: Start metoprolol tartrate 50 mg every 6 hours, 15 minutes after last IV dose, continue for 48 hours 2, 4
• For patients with partial intolerance: Start 25-50 mg every 6 hours (depending on degree of intolerance) 2, 4
• For severe intolerance: Discontinue metoprolol 4

Maintenance Therapy

• After 48 hours: Transition to 100 mg twice daily 2, 4
• Long-term: Follow heart failure dosing regimen with metoprolol succinate 1

Contraindications to Early IV Metoprolol

• Hypotension or signs of shock 2, 4
• Bradycardia or peripheral signs of shock 2, 4
• More than minimal basal rales (signs of congestive heart failure) 2, 4
• Age >70 years with multiple risk factors 2
• Systolic BP <120 mmHg 2
• Heart rate >110 bpm or <60 bpm 2

Benefits vs. Risks

Benefits:

• Reduces reinfarction rate by 5 per 1000 patients 2
• Reduces ventricular fibrillation by 5 per 1000 patients 2

Risks:

• Increases cardiogenic shock by 11 per 1000 patients, particularly in first 24 hours 2
• 30% relative increase in cardiogenic shock overall, especially in high-risk patients 2

Critical Warnings

Never Abruptly Discontinue Metoprolol

• Abrupt cessation can cause severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias 1, 2
• Beta-blocker withdrawal is associated with 2.7-fold increased risk of 1-year mortality compared to continuous use 2
• One study reported 50% mortality rate following abrupt discontinuation 2
• If discontinuation necessary, taper dose by 25-50% every 1-2 weeks 2

Formulation Matters

• Only metoprolol succinate (CR/XL) has proven mortality reduction in heart failure 1, 2
• Metoprolol tartrate should not be used for heart failure management 1, 2
• The three evidence-based beta-blockers with proven mortality benefit in HFrEF are bisoprolol, carvedilol, and metoprolol succinate 1, 2

Pharmacokinetic Considerations

• Oral bioavailability approximately 50% due to pre-systemic metabolism 4
• Elimination half-life: 3-4 hours in extensive metabolizers, 7-9 hours in poor CYP2D6 metabolizers 4
• Poor CYP2D6 metabolizers (8% of Caucasians, 2% of other populations) exhibit several-fold higher plasma concentrations 4
• Hepatic impairment significantly prolongs elimination half-life (up to 7.2 hours)—initiate at low doses with cautious titration 4
• No dose adjustment needed for renal impairment 4