Metoprolol Tartrate

Approved Indications:

A. Cardiovascular Disorders

• Hypertension: Management of mild to moderate hypertension; can be used alone or in combination with other antihypertensive agents.
• Angina Pectoris: Long-term treatment of angina to reduce chest pain episodes and improve exercise tolerance.
• Myocardial Infarction (MI):
• Acute MI: Early and late treatment to reduce cardiovascular mortality.
• Secondary prevention post-MI.

B. Arrhythmias

• Supraventricular Tachycardia (SVT) and other symptomatic tachyarrhythmias, including atrial fibrillation and flutter (rate control).

C. Heart Failure (select cases)

• Off-label short-term rate control in acute decompensated heart failure when hemodynamically stable.

Off-Label / Clinically Accepted Uses:

• Migraine prophylaxis
• Essential tremor
• Thyrotoxicosis/Thyroid storm (to control tachycardia and adrenergic symptoms)
• Anxiety (situational): Performance anxiety-related tachycardia
• Pheochromocytoma (adjunctive): Only after adequate alpha blockade

Route: Oral (tablet, immediate-release), Intravenous (IV)

Adults:

• Hypertension:
• Oral: 50–100 mg twice daily; may increase at weekly intervals to max 450 mg/day (in divided doses)
• Angina Pectoris:
• Oral: 50–100 mg two or three times daily; maximum 400 mg/day
• Acute Myocardial Infarction:
• Initial IV: 5 mg every 2 minutes × 3 doses (15 mg total), followed by:
• Oral: 25–50 mg every 6 hours after 15 minutes of final IV dose
• Maintenance: 100 mg twice daily
• Arrhythmias:
• IV: 2.5–5 mg every 2–5 minutes; max total dose 15 mg
• Migraine Prophylaxis (off-label):
• Oral: 25–100 mg twice daily
• Thyrotoxicosis (off-label):
• Oral: 25–50 mg every 6–8 hours as needed

Pediatrics:

• Not FDA approved for pediatric use, but occasionally used off-label under specialist supervision:
• Oral: 1–2 mg/kg/day in 2–3 divided doses (Max: 6 mg/kg/day or 200 mg/day)

Elderly:

• Start at the lower end of dosage range; monitor heart rate and blood pressure closely

Renal Impairment:

• No dose adjustment typically required

Hepatic Impairment:

• Use cautiously; extensive hepatic metabolism; monitor for accumulation and bradycardia

Administration Notes:

• Take with or immediately following meals
• Do not crush or chew extended-release forms (not applicable to tartrate, which is IR)
• IV form should be administered slowly under cardiac monitoring

Metoprolol tartrate is a selective β1-adrenergic receptor antagonist that primarily affects cardiac tissue. By blocking β1 receptors, it reduces the effect of catecholamines (epinephrine and norepinephrine), thereby decreasing heart rate, myocardial contractility, and cardiac output. This leads to reduced oxygen demand and lower blood pressure. At higher doses, it may also affect β2 receptors. The net therapeutic effect includes decreased myocardial workload, improved arrhythmia control, and prevention of post-infarct mortality.

• Absorption: Rapid and nearly complete oral absorption
• Bioavailability: ~50% (due to significant first-pass hepatic metabolism)
• Onset of Action: Oral – 1 hour; IV – immediate
• Peak Plasma Time: 1.5–2 hours (oral)
• Duration of Action: 5–8 hours (oral)
• Distribution: Vd ~3.2–5.6 L/kg; crosses blood-brain barrier
• Protein Binding: ~12%
• Metabolism: Extensively metabolized in liver, primarily by CYP2D6
• Half-life: 3–7 hours (shorter than metoprolol succinate)
• Excretion: Primarily renal as metabolites (<5% unchanged drug)

• Pregnancy Category: Category C (FDA). Use only if benefits outweigh potential risks. May cause fetal bradycardia, hypoglycemia, and low birth weight with prolonged use.
• Lactation: Metoprolol is excreted into breast milk in small amounts. Generally considered safe during breastfeeding; monitor infant for bradycardia or feeding difficulties.

• Primary Class: Beta-Adrenergic Blocker (Beta-blocker)
• Subclass: Cardioselective (β1-selective), immediate-release formulation

• Hypersensitivity to metoprolol or other beta-blockers
• Sinus bradycardia
• Second- or third-degree heart block (without pacemaker)
• Overt heart failure or cardiogenic shock
• Sick sinus syndrome (unless pacemaker present)
• Severe peripheral arterial circulatory disorders
• Untreated pheochromocytoma (without alpha-blocker)

• Abrupt withdrawal may precipitate angina or myocardial infarction—taper gradually over 1–2 weeks
• Bradycardia, AV block, and hypotension: Monitor ECG and vitals during IV administration
• Use with caution in asthma or COPD: Though β1-selective, selectivity is not absolute
• Diabetes: May mask signs of hypoglycemia (e.g., tachycardia)
• Thyrotoxicosis: May mask clinical signs
• Peripheral vascular disease: May worsen symptoms due to reduced cardiac output

Common:

• Cardiovascular: Bradycardia, hypotension, fatigue, dizziness
• CNS: Depression, confusion, insomnia, headache
• GI: Nausea, diarrhea, abdominal pain
• Respiratory: Dyspnea (less common)

Serious/Rare:

• Heart block, heart failure exacerbation
• Bronchospasm (especially in asthma patients)
• Hypoglycemia (rare, mostly in pediatric or diabetic patients)
• Cold extremities, Raynaud's phenomenon
• Depression, hallucinations (rare CNS effects)
• Erectile dysfunction

Dose-Dependent Effects: Bradycardia and hypotension are more common at higher doses

• CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine): May increase plasma metoprolol levels
• Calcium Channel Blockers (e.g., verapamil, diltiazem): Additive negative chronotropic and inotropic effects—risk of bradycardia or AV block
• Clonidine: Withdrawal of clonidine while on metoprolol may result in rebound hypertension
• Digoxin: Increased risk of bradycardia
• NSAIDs: May reduce antihypertensive efficacy
• Insulin and antidiabetic agents: May mask hypoglycemia symptoms

Enzyme Involvement: Substrate of CYP2D6

• AHA/ACC Hypertension Guidelines: Beta-blockers no longer first-line for uncomplicated hypertension unless comorbid CAD or heart failure is present
• Post-MI Use: Still strongly recommended for reducing mortality
• ESC 2021 Guidelines: Emphasize cardioselective beta-blockers like metoprolol as safer in COPD/asthma patients when needed
• Safety Alerts: Reinforced warnings regarding abrupt withdrawal and bradyarrhythmias

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Humidity: Protect from excessive moisture
• Light Protection: Store in original container; keep tightly closed
• IV Formulation: Use immediately after opening; discard unused portion
• Reconstitution: Not applicable (metoprolol tartrate is supplied as solution or tablets)