What is the appropriate dose of Metoprolol (beta-blocker) for a patient with hypertension or angina, and how should it be adjusted in cases of heart failure or impaired renal function?

Metoprolol Dosing Guidelines

For hypertension, start metoprolol tartrate at 25-50 mg twice daily or metoprolol succinate (extended-release) at 50-200 mg once daily, with maximum doses of 200 mg daily for tartrate and 400 mg daily for succinate. 1, 2

Initial Dosing by Indication

Hypertension

• Metoprolol tartrate (immediate-release): 25-50 mg twice daily initially 1, 2
• Metoprolol succinate (extended-release): 50-200 mg once daily initially 1, 2
• Maximum doses: 200 mg daily for tartrate, 400 mg daily for succinate 1, 2
• Titrate every 1-2 weeks based on blood pressure response 1
• Target blood pressure reduction of at least 20/10 mmHg, ideally to <140/90 mmHg (current guidelines recommend <130/80 mmHg) 1, 2

Angina Pectoris

• Initial dose: 25-50 mg twice daily for metoprolol tartrate 1
• Extended-release: 50-200 mg once daily for metoprolol succinate 1
• Titrate gradually every 1-2 weeks as tolerated 1
• Target dose: 200 mg daily 1
• Target resting heart rate of 50-60 beats per minute unless limiting side effects occur 1, 2

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Critical formulation requirement: Only metoprolol succinate extended-release is proven to reduce mortality in heart failure—metoprolol tartrate should NOT be used 3
• Initial dose: 12.5-25 mg once daily of metoprolol succinate 1, 3
• Titration schedule: Double the dose every 2 weeks if well tolerated (12.5 mg → 25 mg → 50 mg → 100 mg → 200 mg) 1, 3
• Target dose: 200 mg once daily 1, 3
• If target dose cannot be achieved, aim for at least 50% (100 mg daily minimum) as dose-response relationships exist for mortality benefit 1, 3
• Achieved 34% reduction in all-cause mortality in the MERIT-HF trial 1, 3

Atrial Fibrillation Rate Control

• Metoprolol tartrate: 25-100 mg twice daily 1
• Metoprolol succinate: 50-400 mg once daily 1
• Target resting heart rate <80 bpm (strict control) or <110 bpm (lenient control) 1

Acute Myocardial Infarction

• IV phase: 5 mg IV bolus over 1-2 minutes, repeated every 5 minutes for up to 3 doses (maximum 15 mg total) 1, 4
• Oral phase: Begin 15 minutes after last IV dose with 50 mg every 6 hours for 48 hours 1, 4
• Maintenance: 100 mg twice daily thereafter 1

Absolute Contraindications (Hold Parameters)

Do not administer metoprolol if any of the following are present: 1, 2

• Signs of heart failure, low output state, or decompensated heart failure 1, 2
• Systolic BP <100-120 mmHg (depending on clinical context) 1, 2
• Heart rate <50-60 bpm with symptoms (symptomatic bradycardia) 1, 2
• PR interval >0.24 seconds 1, 2
• Second or third-degree heart block without functioning pacemaker 1, 2
• Active asthma or reactive airways disease 1, 2
• Cardiogenic shock or high risk factors (age >70 years, HR >110 bpm or <60 bpm, Killip class >1) 1, 2

Special Population Adjustments

Renal Impairment

• No dose adjustment required 4
• Systemic availability and half-life do not differ clinically from normal subjects 4

Hepatic Impairment

• Initiate at low doses with cautious gradual titration 4
• Elimination half-life considerably prolonged (up to 7.2 hours) depending on severity 4
• Blood levels likely to increase substantially 4

Elderly Patients (>65 years)

• Start with low initial doses 4
• Greater frequency of decreased hepatic, renal, or cardiac function 4
• Plasma concentrations may be slightly higher due to decreased metabolism and hepatic blood flow, though not clinically significant 4

Women

• Metoprolol exposure is 50-80% higher in women than men 1
• Women with heart failure may achieve optimal outcomes at 50% of guideline-recommended doses 1
• Consider 50% dose reduction on average to reduce adverse drug reactions while maintaining efficacy 1

Critical Monitoring Parameters

During Initiation and Titration

• Blood pressure and heart rate at each visit 1, 2
• ECG monitoring during IV administration 1, 2
• Auscultation for rales (pulmonary congestion) during IV therapy 1
• Auscultation for bronchospasm 1
• Signs of worsening heart failure (dyspnea, weight gain >1.5-2.0 kg over 2 days, peripheral edema) 1

Ongoing Monitoring

• Daily weights for heart failure patients 1
• Symptomatic bradycardia (HR <60 bpm with dizziness, lightheadedness, syncope) 1
• Symptomatic hypotension (SBP <100 mmHg with dizziness, lightheadedness, blurred vision) 1
• Delayed adverse effects like fatigue or weakness (may appear within 2-3 weeks) 1

Management of Adverse Effects

Symptomatic Bradycardia (HR <50 bpm with symptoms)

• First-line: Reduce metoprolol dose by 50% 1
• Hold completely if: SBP <100 mmHg with symptoms or evidence of hypoperfusion 1
• Never abruptly discontinue: Risk of severe exacerbation of angina, MI, ventricular arrhythmias, and 50% mortality rate in one study 1

Symptomatic Hypotension

• First: Reduce or eliminate vasodilators (nitrates, calcium channel blockers) 3
• Second: If no congestion present, reduce diuretic dose 3
• Third: Only if above measures fail, temporarily reduce metoprolol dose by 50% 3
• Asymptomatic low BP requires no change 3

Worsening Heart Failure During Titration

• First: Double diuretic dose 1, 3
• Second: Halve metoprolol dose only if increasing diuretic fails 1, 3
• Maintain some beta-blockade as complete discontinuation increases mortality risk 2.7-fold 1

Common Pitfalls to Avoid

• Never give full 15 mg IV dose rapidly or as single bolus—significantly increases hypotension and bradycardia risk 1
• Never use metoprolol tartrate for heart failure—only metoprolol succinate has proven mortality reduction 3
• Never abruptly discontinue—causes rebound hypertension, angina exacerbation, MI, and ventricular arrhythmias 1, 3
• Never administer IV metoprolol in decompensated heart failure—increases cardiogenic shock risk 1, 2
• Never use in pre-excited atrial fibrillation (WPW syndrome)—may paradoxically accelerate ventricular response 1
• Avoid underdosing in heart failure—aim for at least 50% of target dose (100 mg daily minimum) for mortality benefit 1, 3

Pharmacokinetic Considerations

• Half-life: 3-4 hours (7-9 hours in poor CYP2D6 metabolizers) 4
• Metabolism: Primarily by CYP2D6 4
• Poor metabolizers (8% Caucasians, 2% other populations): Exhibit several-fold higher plasma concentrations, decreasing cardioselectivity 4
• Bioavailability: Crosses placenta, found in breast milk, crosses blood-brain barrier 4