metoprolol succinate
Toprol XL

metoprolol tartrate
Lopressor

Available forms
Available by prescription only
Injection: 1 mg/ml in 5-ml ampules or prefilled syringes
Tablets: 50 mg, 100 mg
Tablets (extended-release): 25 mg, 50 mg, 100 mg, 200 mg

Indications and dosages
 Mild to severe hypertension. Adults: Initially, 50 to 100 mg P.O. daily in single or divided doses; usual maintenance dosage is 100 to 450 mg daily. Or, 50 to 100 mg P.O. extended-release tablets daily (maximum dose, 400 mg daily). Dosages may be increased weekly or longer as needed to desired effect.
 Early intervention in acute MI. Adults: 2.5 to 5 mg I.V. bolus at 2- to 5-minute intervals up to a total of 15 mg over 10 to 15 minutes. Then give 50 mg P.O. 15 minutes after the last I.V. dose, and continue 50 mg P.O. every 6 hours for 48 hours. Maintenance dosage, 100 mg, b.i.d., P.O. or 200 mg of sustained release form P.O. daily.
 Late intervention in acute MI. Adults: 100 mg P.O. b.i.d. for at least 3 months.
 Atrial tachyarrhythmias following acute MI ◇. Adults: 2.5 to 5 mg I.V. q 2 to 5 minutes to control rate up to 15 mg over 10 to 15 minutes. Discontinue when therapeutic efficacy is achieved or if systolic blood pressure is less than 100 mm Hg or heart rate is less than 50 beats/minute.
 Angina. Adults: 100 mg P.O. daily in two divided doses. Maintenance dosage, 100 to 400 mg daily. Or, 100 mg P.O. extended-release tablets daily (maximum dose, 400 mg daily). Dosages may be increased gradually at weekly intervals p.r.n.
 Stable, symptomatic heart failure of ischemic, hypertensive, or cardiomyopathic origin. Adults: Using extended-release form, 25 mg P.O. once daily for 2 weeks in patients with New York Heart Association class II heart failure, and 12.5 mg P.O. once daily in patients with more severe heart failure. Double the dose every 2 weeks to the highest tolerable dose, up to 200 mg.

Pharmacodynamics
Antihypertensive action: Metoprolol is classified as a cardioselective beta₁ antagonist; exact mechanism of antihypertensive effect is unknown. Drug may reduce blood pressure by blocking adrenergic receptors, thus decreasing cardiac output; by decreasing sympathetic outflow from the CNS; or by suppressing renin release.
Action after acute MI: The exact mechanism by which metoprolol decreases mortality after MI is unknown. In patients with MI, it reduces heart rate, systolic blood pressure, and cardiac output. Drug also appears to decrease the occurrence of ventricular fibrillation in these patients.

Pharmacokinetics
Absorption: Orally administered metoprolol is absorbed rapidly and almost completely from GI tract; food enhances absorption.
Distribution: Distributed widely throughout the body; about 12% is protein-bound.
Metabolism: Metabolized in the liver to inactive metabolites.
Excretion: About 95% of a given dose of metoprolol is excreted in urine within 72 hours, largely as metabolites.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other beta blockers. Also contraindicated in patients with sinus bradycardia, heart block greater than first-degree, cardiogenic shock, or overt cardiac failure when used to treat hypertension or angina. When used to treat MI, drug also is contraindicated in patients with heart rate less than 45 beats/minute, second- or third-degree heart block, PR interval of 0.24 second or longer with first-degree heart block, systolic blood pressure less than 100 mm Hg, or moderate to severe cardiac failure.
  Use cautiously in patients with diabetes mellitus, impaired hepatic or respiratory function, diabetes, or heart failure.

Interactions
Drug-drug. Amiodarone: Increases effects of metoprolol. Monitor patient closely.
Antihypertensives, diuretics: Potentiates antihypertensive effects. Monitor blood pressure.
Barbiturates: Decreases effect of metoprolol. Monitor for drug effect.
Benzodiazepines: Increases effects of benzodiazepines. Use together cautiously.
Cardiac glycosides: Enhances bradycardia. Monitor vital signs closely.
Clonidine: May cause potentially fatal increases in blood pressure after discontinuation of clonidine or after simultaneous withdrawal. Use together cautiously.
Ergot alkaloids: Increases risk of peripheral ischemia. Use together cautiously.
MAO inhibitors: Increases risk of bradycardia. Avoid use together.
Selected serotonin reuptake inhibitors: Increases risk of excessive beta blockade. Use together cautiously.
Sulfonylureas: Increases risk of hypoglycemia. Monitor blood glucose level.
Sympathomimetics: Antagonizes beta-adrenergic effects of sympathomimetics. Monitor patient for drug effect.
Verapamil: May increase bioavailability of metoprolol when given together. Avoid use together if possible. If used together, monitor patient closely and adjust metoprolol dose.
Drug-lifestyle. Smoking: May alter effects of metoprolol. Discourage smoking. Dosage adjustments may be needed.

Adverse reactions
CNS: fatigue, dizziness, depression, insomnia, headaches, nightmares, drowsiness.
CV: bradycardia, hypotension, heart failure, cold limbs, Raynaud’s disease, arrhythmias.
GI: nausea, diarrhea, constipation, flatulence.
Respiratory: dyspnea, bronchospasm.
Skin: rash.
Other: decreased libido.

Effects on lab test results
• May increase transaminase, alkaline phosphatase, LDH, and uric acid levels.

Overdose and treatment
Signs and symptoms of overdose include severe hypotension, bradycardia, heart failure, and bronchospasm.
 After acute ingestion, empty stomach by induced emesis or gastric lavage, and give activated charcoal to reduce absorption. Subsequent treatment is usually symptomatic and supportive.

Special considerations
• When used for angina, use only if AV block and left ventricular dysfunction aren’t present.
• If heart failure worsens, increase diuretic doses and consider lowering dose of Toprol XL or temporarily discontinuing it. Don’t increase dose until symptoms of worsening heart failure are stabilized.
• Decrease dose of Toprol XL if patient with heart failure experiences symptomatic bradycardia.
• Administer drug with meals to enhance absorption.
• Reduce dosage in patients with impaired hepatic function.
• Avoid late-evening doses to minimize insomnia.
• Monitor heart rate, blood pressure, and ECG during I.V. administration.
• Check blood pressure during dosage adjustment and every 3 to 6 months during maintenance therapy.
• Assess patient for signs of mental depression.
• Store drug at 59° to 86° F (15° to 30° C).
 ALERT Don’t confuse Toprol XL (metoprolol) with Topamax (topiramate).
Breast-feeding patients
• Metoprolol appears in breast milk. Recommend an alternative to breast-feeding during therapy.
Pediatric patients
• Safety and efficacy in children haven’t been established. No dosage recommendation exists for children.
Geriatric patients
• Geriatric patients may need lower maintenance dosages of metoprolol because of delayed metabolism; they also may have enhanced adverse effects. Use cautiously.

Patient education
• Instruct patient to take drug exactly as prescribed and to take it with meals. • Inform patient not to stop drug abruptly and to report adverse reactions. Inform him that drug must be withdrawn gradually over 1 to 2 weeks.
• Inform diabetic patient that drug may mask signs and symptoms of hypoglycemia.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use