Metoprolol

Pronunciation: MET-oh-PROE-lol
Class: Beta-adrenergic blocking agent

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Trade Names

Lopressor
- Tablets 50 mg
- Tablets 100 mg
- Injection 1 mg/mL

Metoprolol Tartrate
- Tablets 25 mg

Toprol XL
- Tablets, ER 25 mg (metoprolol succinate 23.75 mg equivalent to metoprolol tartrate 25 mg)
- Tablets, ER 50 mg (metoprolol succinate 47.5 mg equivalent to metoprolol tartrate 50 mg)
- Tablets, ER 100 mg (metoprolol succinate 95 mg equivalent to metoprolol tartrate 100 mg)
- Tablets, ER 200 mg (metoprolol succinate 190 mg equivalent to metoprolol tartrate 200 mg)

Apo-Metoprolol (Canada)
Apo-Metoprolol SR (Canada)
Betaloc (Canada)
Betaloc Durules (Canada)
Gen-Metoprolol (Type L) (Canada)
Novo-Metoprol (Canada)
Nu-Metop (Canada)
PMS-Metoprolol-L (Canada)
Sandoz Metoprolol (Type L) (Canada)

Pharmacology

Blocks beta receptors, primarily affecting CV system (decreases heart rate, contractility, and BP) and lungs (promotes bronchospasm).

Pharmacokinetics

Absorption

95% is absorbed; oral bioavailability is 40% to 50%.

Distribution

12% is protein bound; rapidly enters the CNS, and has moderate lipid solubility.

Metabolism

Metabolized hepatically (primarily by CYP2D6).

Elimination

Elimination is mainly by biotransformation in the liver. Approximately 95% excreted renally and less than 5% unchanged in urine. The half-life is 3 to 7 h.

Peak

Times to peak are 1 to 2 h (oral, regular), 6 to 12 h (oral, long-acting), and 20 min (IV).

Indications and Usage

Used alone or in combination with other antihypertensive agents for management of hypertension; long-term management of angina pectoris; MI (immediate-release tablets and injection); treatment of stable, symptomatic (New York Heart Association [NYHA] class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin ( Toprol XL only).

Unlabeled Uses

Acute coronary syndrome (ST-elevation MI, non–ST-elevation MI, and unstable angina); atrial fibrillation; prevention of migraine.

Contraindications

Greater than first-degree heart block; significant first-degree heart block (PR interval of 0.24 sec or longer); CHF unless secondary to tachyarrhythmia treatable with beta-blockers; overt or moderate to severe cardiac failure; sick sinus syndrome (unless a permanent pacemaker is in place); sinus bradycardia; cardiogenic shock; hypersensitivity to beta-blockers; systolic BP below 100 mm Hg; heart rate less than 45 bpm; severe peripheral arterial circulatory disorders; second- and third-degree heart block; pheochromocytoma.

Dosage and Administration

Hypertension
Adults Initial

PO 100 mg/day in single or divided doses. Give 50 to 100 mg/day in a single-dose ER tablet.

Maintenance

PO 100 to 450 mg/day.

Children 6 to 16 yr of age Initial

PO 1 mg/kg once daily; max, 50 mg once daily.

Maintenance

Up to 2 mg/kg (or 200 mg) once daily.

Angina
Adults Initial

PO 100 mg/day in 2 divided doses. 100 mg/day in a single-dose ER tablet.

Maintenance

PO 100 to 400 mg/day.

MI
Adults

IV bolus injection 5 mg slowly; may repeat every 2 min up to 15 mg. If tolerated, give PO 50 mg every 6 h beginning 15 min after last IV dose; continue for 48 h followed by PO 100 mg twice daily for 1 to 3 yr. If patient is intolerant of full IV dose, give PO 25 to 50 mg every 6 h starting 15 min after last IV dose.

CHF
Adults ER tablet

PO Start with 25 mg daily for 2 wk in patients with NYHA class II heart failure and 12.5 mg daily in patients with more severe heart failure, then double the dose every 2 wk to highest dosage tolerated by patient (max, 200 mg).

Off-label dosing
Acute coronary syndrome (ST-elevation MI, non–ST-elevation MI, and unstable angina)

5 mg by slow IV push at 5-min intervals to a total of 15 mg.

Atrial fibrillation

2.5 mg to 5 mg IV bolus over 2 min, repeat every 5 min, up to 3 doses.

Prevention of migraine Adults

PO 100 to 200 mg daily.

Storage/Stability

Store at 59° to 86°F and protect from light.

Drug Interactions

Barbiturates

Bioavailability of metoprolol may decrease.

Bupropion, diphenhydramine, fluoxetine, hydroxychloroquine, methimazole, paroxetine, propafenone, propylthiouracil, quinidine, ritonavir, terbinafine, thioridazine

Effects of metoprolol may increase.

Cimetidine

May increase metoprolol levels.

Clonidine

May enhance or reverse antihypertensive effect; potentially life-threatening situations may occur, especially on abrupt withdrawal of clonidine.

Digitalis glycosides

Concomitant use may increase the risk of bradycardia.

General anesthetics

May enhance the cardiodepressant effect of beta-blockers.

Hydralazine

Serum levels of both drugs may increase.

Lidocaine

Lidocaine levels may increase, leading to toxicity.

NSAIDs

Some agents may impair antihypertensive effect.

Prazosin

Orthostatic hypotension may increase.

Rifampin

May decrease effects of metoprolol.

Verapamil

Effects of both drugs may be increased.

Laboratory Test Interactions

Antinuclear antibodies may develop but are usually reversible on discontinuation.

Adverse Reactions

Cardiovascular

Bradycardia, edema, flushing, hypotension (3%); arterial insufficiency; CHF; palpitations; peripheral edema.

CNS

Dizziness, fatigue, headache, sleepiness (10%); depression (5%); drowsiness; forgetfulness; lethargy; paresthesias; vertigo.

Dermatologic

Pruritus, rash (5%); alopecia; facial erythema; urticaria.

EENT

Dry eyes; visual disturbances.

GI

Diarrhea, nausea, vomiting (5%); constipation; dry mouth; flatulence; gastric pain; heartburn.

Genitourinary

Difficulty with urination; impotence; urinary retention.

Respiratory

Shortness of breath (3%); bronchospasm; dyspnea; wheezing.

Miscellaneous

Asthenia; cold extremities; increased hypoglycemic response to insulin; may mask hypoglycemic signs; muscle cramps; systemic lupus erythematosus.

Precautions

Warnings

Ischemic heart disease

In patients with angina pectoris or coronary artery disease (CAD), metoprolol may cause exacerbation of angina, occurrence of MI, and ventricular arrhythmias. Monitor patients closely because CAD is common and often unrecognized; it may be prudent not to discontinue beta-blocker therapy abruptly in patients being treated for hypertension.

Bronchospastic disease

In general, do not give beta-blockers to patients with bronchospastic disease.

Major surgery

The necessity of withdrawing beta-blocker therapy prior to surgery is controversial; the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Diabetes and hypoglycemia

Use with caution in diabetic patients if a beta-blocker is required. Beta-blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly altered.

Pheochromocytoma

Use is contraindicated in patients with pheochromocytoma.

Thyrotoxicosis

Beta-blockers may mask certain clinical signs (eg, tachycardia) of hyperthyroidism. Carefully manage patients suspected of developing thyrotoxicosis to avoid abrupt withdrawal of beta blockade, which might precipitate a thyroid storm.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established (immediate-release); safety and efficacy not established in children younger than 6 yr of age (ER).

Hypersensitivity

While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic.

Hepatic Function

Use with caution; reduced daily dose is advised.

Anaphylaxis

Deaths have occurred; aggressive therapy may be required.

Atrioventricular block

Slows AV conduction and may cause heart block.

Bradycardia

Metoprolol decreases heart rate in most patients.

Cardiac failure

Beta-blockers depress myocardial contractility and may precipitate or exacerbate cardiac failure.

CHF

Administer cautiously in CHF patients controlled by digitalis and diuretics.

Hypokalemia

Transient decreases in serum potassium levels may occur caused by intracellular shunting, which can produce adverse CV effects.

Hypotension

If systolic blood pressure decreases to 90 mm Hg or less, discontinue metoprolol.

Peripheral vascular disease

May precipitate or aggravate symptoms of atrial insufficiency.

Overdosage

Symptoms

Atrioventricular block, bradycardia, bronchospasm, cardiac arrest, cardiac failure, cardiogenic shock, cyanosis, hypotension, impairment of consciousness/coma, nausea, and vomiting.

Patient Information

Teach patient how to check pulse and BP.
Advise patient to contact health care provider if pulse is less than 50 bpm.
Explain why medication should not be discontinued abruptly.
Tell diabetic patient to check blood sugar regularly and consult health care provider if levels are unstable.
Explain that adverse reactions are usually mild and transient and will generally subside with continued therapy.
Instruct patient to report the following symptoms to health care provider: difficulty breathing, edema, night cough.
Advise patient that drug may cause drowsiness and to use caution while driving or performing tasks requiring mental alertness.