Professional Information

Metoprolol

Pronunciation: (meh-TOE-pro-lahl)
Class: Beta-adrenergic blocking agent

Trade Names:
Lopressor
- Tablets 50 mg
- Tablets 100 mg
- Injection 1 mg/mL

Trade Names:
Toprol XL
- Tablets, extended release 25 mg (23.75 mg metoprolol succinate equivalent to 25 mg metoprolol tartrate)
- Tablets, extended release 50 mg (47.5 mg metoprolol succinate equivalent to 50 mg metoprolol tartrate)
- Tablets, extended release 100 mg (95 mg metoprolol succinate equivalent to 100 mg metoprolol tartrate)
- Tablets, extended release 200 mg (190 mg metoprolol succinate equivalent to 200 mg metoprolol tartrate)

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, decreases contractility, decreases 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 t _½ 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 (NYHA class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin ( Toprol-XL 25 mg only).

Contraindications

Greater than first-degree heart block; CHF unless secondary to tachyarrhythmia treatable with beta-blockers; overt or moderate to severe cardiac failure; sinus bradycardia; cardiogenic shock; hypersensitivity to beta-blockers; systolic BP below 100 mm Hg; MI in patients with heart rate less than 45 bpm.

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, extended-release tablet.

Maintenance

PO 100 to 450 mg/day.

Angina
Adults Initial

PO 100 mg/day in 2 divided doses. 100 mg/day in a single dose, extended-release 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 Extended-release 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).

Storage/Stability

Store at room temperature (59° to 86°F) and protect from light.

Drug Interactions

Barbiturates

Bioavailability of metoprolol may decrease.

Cimetidine

May increase metoprolol levels.

Clonidine

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

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.

Methimazole, propafenone, propylthiouracil, quinidine

Effects of metoprolol 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

Hypotension; edema; flushing; bradycardia (3%); palpitations; CHF; arterial insufficiency; peripheral edema.

CNS

Headache; fatigue; dizziness (10%); depression (5%); lethargy; drowsiness; forgetfulness; sleepiness (10%); vertigo; paresthesias.

Dermatologic

Rash (5%); facial erythema; alopecia; urticaria; pruritus (5%).

EENT

Dry eyes; visual disturbances.

GI

Nausea; vomiting; diarrhea (5%); dry mouth; gastric pain; constipation; heartburn; flatulence.

Genitourinary

Impotence; urinary retention; difficulty with urination.

Respiratory

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

Miscellaneous

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

Precautions

Warnings

Abrupt withdrawal

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.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

Hepatic Function

Reduced daily dose advised.

Anaphylaxis

Deaths have occurred; aggressive therapy may be required.

AV block

Slows AV conduction and may cause heart block.

Bradycardia

Metoprolol decreases heart rate in most patients.

Bronchospastic disease

Use with caution. Administer in smaller divided doses.

CHF

Administer cautiously in CHF patients controlled by digitalis and diuretics. Notify health care provider at first sign or symptom of CHF or of unexplained respiratory symptoms in any patient.

Diabetes

May mask tachycardia associated with hypoglycemia.

Hypokalemia

Usually transient decreases in serum potassium levels may occur caused by intracellular shunting, which can produce adverse cardiovascular effects.

Peripheral vascular disease

May precipitate or aggravate symptoms of atrial insufficiency.

Thyrotoxicosis

May mask clinical signs (eg, tachycardia) of developing or continuing hyperthyroidism. Abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm.

Overdosage

Symptoms

Bradycardia, hypotension, bronchospasm, cardiac failure.

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, night cough, edema.
Advise patient that drug may cause drowsiness and to use caution while driving or performing tasks requiring mental alertness.
Instruct patient not to take OTC cold preparations without consulting health care provider.