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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(me toe PROE lole)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of angina pectoris, hypertension, or hemodynamically-stable acute myocardial infarction
Extended release: Treatment of angina pectoris or hypertension; to reduce mortality/hospitalization in patients with heart failure (stable NYHA Class II or III) already receiving ACE inhibitors, diuretics, and/or digoxin
Use: Unlabeled
Treatment of ventricular arrhythmias, atrial ectopy; migraine prophylaxis, essential tremor, aggressive behavior (not recommended for dementia-associated aggression); prevention of reinfarction and sudden death after myocardial infarction; prevention and treatment of atrial fibrillation and atrial flutter; multifocal atrial tachycardia; symptomatic treatment of hypertrophic obstructive cardiomyopathy; management of thyrotoxicosis
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in animal studies; therefore, the manufacturer classifies metoprolol as pregnancy category C. Metoprolol crosses the placenta and can be detected in cord blood, amniotic fluid, and the serum of newborn infants. In a cohort study, an increased risk of cardiovascular defects was observed following maternal use of beta-blockers during pregnancy. Intrauterine growth restriction (IUGR), small placentas, as well as fetal/neonatal bradycardia, hypoglycemia, and/or respiratory depression have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth should be available. Untreated chronic maternal hypertension and pre-eclampsia are also associated with adverse events in the fetus, infant, and mother. The clearance of metoprolol is increased and serum concentrations and AUC of metoprolol are decreased during pregnancy. Metoprolol has been evaluated for the treatment of hypertension in pregnancy, but other agents may be more appropriate for use.
Lactation
Enters breast milk/use caution (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Small amounts of metoprolol can be detected in breast milk. The manufacturer recommends that caution be exercised when administering metoprolol to nursing women.
Contraindications
Hypersensitivity to metoprolol, any component of the formulation, or other beta-blockers
Note: Additional contraindications are formulation and/or indication specific.
Immediate release tablets/injectable formulation:
Hypertension and angina: Sinus bradycardia; second- and third-degree heart block; cardiogenic shock; overt heart failure; sick sinus syndrome (except in patients with a functioning artificial pacemaker); severe peripheral arterial disease; pheochromocytoma (without alpha blockade)
Myocardial infarction: Severe sinus bradycardia (heart rate <45 beats/minute); significant first-degree heart block (P-R interval ≥0.24 seconds); second- and third-degree heart block; systolic blood pressure <100 mm Hg; moderate-to-severe cardiac failure
Extended release tablet: Severe bradycardia, second- and third degree heart block; cardiogenic shock; decompensated heart failure; sick sinus syndrome (except in patients with a functioning artificial pacemaker)
Warnings/Precautions
Boxed warnings:
• Abrupt withdrawal: See “Other warnings/precautions” below.
Concerns related to adverse events:
• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated allergen challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
• Atrioventricular (AV) block: Metoprolol commonly produces mild first-degree heart block (P-R interval >0.2-0.24 sec). Metoprolol may also produce severe first- (P-R interval ≥0.26 sec), second-, or third-degree heart block. Patients with acute myocardial infarction (especially right ventricular myocardial infarction) have a high risk of developing heart block of varying degrees. If severe heart block occurs, metoprolol should be discontinued and measures to increase heart rate should be employed.
• Hypotension: Symptomatic hypotension may occur with use.
Disease-related concerns:
• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; however, metoprolol, with B1 selectivity, has been used cautiously with close monitoring.
• Conduction abnormality: Consider pre-existing conditions such as sick sinus syndrome before initiating.
• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
• Heart failure: Use with caution in patients with compensated heart failure; monitor for a worsening of heart failure (only the extended release product is indicated for use in heart failure).
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis.
• Peripheral vascular disease (PVD) and Raynaud's disease: Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's disease. Use with caution and monitor for progression of arterial obstruction.
• Pheochromocytoma (untreated): Adequate alpha-blockade is required prior to use of any beta-blocker.
• Psoriasis: Beta-blocker use has been associated with induction or exacerbation of psoriasis, but cause and effect have not been firmly established.
• Psychiatric disease: Use with caution in patients with a history of psychiatric illness; may cause or exacerbate CNS depression.
• Thyroid disease: May mask signs of hyperthyroidism (eg, tachycardia). If hyperthyroidism is suspected, carefully manage and monitor; abrupt withdrawal may exacerbate symptoms of hyperthyroidism or precipitate thyroid storm. Alterations in thyroid function tests may be observed.
Concurrent drug therapy issues:
• Calcium channel blockers (nondihydropyridines): Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur. Avoid concurrent I.V. use of both agents.
• Cardiac glycosides: Use with caution in patients receiving digoxin; bradycardia or heart block can occur.
• CYP2D6 inhibitors: Use with caution in patients receiving CYP2D6 inhibitors (eg, bupropion, chlorpromazine, cimetidine, diphenhydramine, hydroxychloroquine, fluoxetine, paroxetine, propafenone, propoxyphene, quinidine, ritonavir, terbinafine, thioridazine); concurrent use may increase metoprolol plasma concentrations.
• Inhaled anesthetic agents: Use with caution in patients receiving inhaled anesthetic agents known to depress myocardial contractility.
Special populations:
• Elderly: Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary.
Dosage form specific issues:
• Extended release: Use care in compensated heart failure and monitor closely for a worsening of the condition. May need to increase diuretics and wait until clinically stable to advance dose to target.
Other warnings/precautions:
• Abrupt withdrawal: [U.S. Boxed Warning]: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered over 1-2 weeks to avoid acute tachycardia, hypertension, and/or ischemia. Severe exacerbation of angina, ventricular arrhythmias, and myocardial infarction (MI) have been reported following abrupt withdrawal of beta-blocker therapy. Temporary but prompt resumption of beta-blocker therapy may be indicated with worsening of angina or acute coronary insufficiency.
• Major surgery: Although perioperative beta-blocker therapy is recommended prior to elective surgery in selected patients, use of high-dose extended release metoprolol in patients naïve to beta-blocker therapy undergoing noncardiac surgery has been associated with bradycardia, hypotension, stroke, and death. Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery.
Adverse Reactions
Frequency may not be defined.
Cardiovascular: Hypotension (1% to 27%), bradycardia (2% to 16%), first-degree heart block (P-R interval ≥0.26 sec; 5%), arterial insufficiency (usually Raynaud type; 1%), chest pain (1%), CHF (1%), edema (peripheral; 1%), palpitation (1%), syncope (1%)
Central nervous system: Dizziness (2% to 10%), fatigue (1% to 10%), depression (5%), confusion, hallucinations, headache, insomnia, memory loss (short-term), nightmares, sleep disturbances, somnolence, vertigo
Dermatology: Pruritus (5%), rash (5%), photosensitivity, psoriasis exacerbated
Endocrine & metabolic: Libido decreased, Peyronie's disease (<1%), diabetes exacerbated
Gastrointestinal: Diarrhea (5%), constipation (1%), flatulence (1%), gastrointestinal pain (1%), heartburn (1%), nausea (1%), xerostomia (1%), vomiting
Hematologic: Claudication
Neuromuscular & skeletal: Musculoskeletal pain
Ocular: Blurred vision, visual disturbances
Otic: Tinnitus
Respiratory: Dyspnea (1% to 3%), bronchospasm (1%), wheezing (1%), rhinitis, shortness of breath
Miscellaneous: Cold extremities (1%)
Postmarketing and/or case reports: Agranulocytosis, alkaline phosphatase increased, alopecia (reversible), anxiety, arthralgia, arthritis, cardiogenic shock, diaphoresis increased, dry eyes, gangrene, hepatitis, HDL decreased, impotence, jaundice, lactate dehydrogenase increased, nervousness, paresthesia, retroperitoneal fibrosis, second-degree heart block, taste disturbance, third-degree heart block, thrombocytopenia, transaminases increased, triglycerides increased, urticaria, vomiting, weight gain
Other events reported with beta-blockers: Catatonia, emotional lability, fever, hypersensitivity reactions, laryngospasm, nonthrombocytopenic purpura, respiratory distress, thrombocytopenic purpura
Metabolism/Transport Effects
Substrate of CYP2C19 (minor), CYP2D6 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (weak)
Drug Interactions
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Risk D: Consider therapy modification
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Alpha-/Beta-Agonists (Direct-Acting): Beta-Blockers may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Exceptions: Dipivefrin. Risk D: Consider therapy modification
Alpha1-Blockers: Beta-Blockers may enhance the orthostatic hypotensive effect of Alpha1-Blockers. The risk associated with ophthalmic products is probably less than systemic products. Risk D: Consider therapy modification
Alpha2-Agonists: Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the alpha2-agonist is abruptly withdrawn. Exceptions: Apraclonidine; Brimonidine. Risk D: Consider therapy modification
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Amiodarone: May enhance the bradycardic effect of Beta-Blockers. Possibly to the point of cardiac arrest. Amiodarone may increase the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
Antipsychotic Agents (Phenothiazines): May enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult product labeling for specific recommendations. Risk C: Monitor therapy
Barbiturates: May decrease the serum concentration of Beta-Blockers. Risk C: Monitor therapy
Beta2-Agonists: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Risk C: Monitor therapy
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Risk C: Monitor therapy
Calcium Channel Blockers (Dihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): May enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Beta-Blockers. Exceptions: Bepridil [Off Market]. Risk C: Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Risk C: Monitor therapy
Cholinergic Agonists: Beta-Blockers may enhance the adverse/toxic effect of Cholinergic Agonists. Of particular concern are the potential for cardiac conduction abnormalities and bronchoconstriction. Management: Administer these agents in combination with caution, and monitor for conduction disturbances. Avoid methacholine with any beta blocker due to the potential for additive bronchoconstriction. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Risk C: Monitor therapy
Dronedarone: May enhance the bradycardic effect of Beta-Blockers. Dronedarone may increase the serum concentration of Beta-Blockers. This likely applies only to those agents that are metabolized by CYP2D6. Management: Use lower initial beta-blocker doses; adequate tolerance of the combination, based on ECG findings, should be confirmed prior to any increase in beta-blocker dose. Risk D: Consider therapy modification
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Risk C: Monitor therapy
Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Risk X: Avoid combination
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Risk C: Monitor therapy
Lidocaine: Beta-Blockers may increase the serum concentration of Lidocaine. Risk C: Monitor therapy
Lidocaine (Systemic): Beta-Blockers may decrease the metabolism of Lidocaine (Systemic). Risk C: Monitor therapy
Lidocaine (Topical): Beta-Blockers may decrease the metabolism of Lidocaine (Topical). Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic hypotensive effect of Orthostatic Hypotension Producing Agents. Risk C: Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Risk C: Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Risk X: Avoid combination
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
QuiNIDine: May decrease the metabolism of Beta-Blockers. Risk C: Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Risk C: Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Risk C: Monitor therapy
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Selective Serotonin Reuptake Inhibitors: May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE. Risk C: Monitor therapy
Sulfonylureas: Beta-Blockers may enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Risk C: Monitor therapy
Theophylline Derivatives: Beta-Blockers (Beta1 Selective) may diminish the bronchodilatory effect of Theophylline Derivatives. Management: Monitor for reduced theophylline efficacy during concomitant use with any beta-blocker. Beta-1 selective agents are less likely to antagonize theophylline than nonselective agents, but selectivity may be lost at higher doses. Risk C: Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Food: Food increases absorption. Metoprolol serum levels may be increased if taken with food. Management: Take immediate release tartrate tablets with food; succinate can be taken with or without food.
Herb/Nutraceutical: Some herbal medications may worsen hypertension (eg, licorice); others may increase the antihypertensive effect of metoprolol (eg, shepherd's purse). Management: Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (American), gotu kola, licorice, and yohimbe. Avoid black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, and shepherd's purse.
Storage
Injection: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.
Tablet: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.
Compatibility
Stable in D5W, NS.
Y-site administration: Compatible: Abciximab, alteplase, amiodarone, argatroban, bivalirudin, eptifibatide, meperidine, milrinone, morphine, procainamide. Incompatible: Amphotericin B cholesteryl sulfate complex, lidocaine, nitroglycerin. Variable (consult detailed reference): Diltiazem, furosemide, heparin, nesiritide, nitroprusside.
Mechanism of Action
Selective inhibitor of beta1-adrenergic receptors; competitively blocks beta1-receptors, with little or no effect on beta2-receptors at doses <100 mg; does not exhibit any membrane stabilizing or intrinsic sympathomimetic activity
Pharmacodynamics/Kinetics
Onset of action: Peak effect: Oral: 1.5-4 hours; I.V.: 20 minutes (when infused over 10 minutes)
Duration: Oral: Immediate release: 10-20 hours, Extended release: ~24 hours; I.V.: 5-8 hours
Absorption: 95%, rapid and complete
Distribution: Vd: 5.5 L/kg
Protein binding: 12% to albumin
Metabolism: Extensively hepatic via CYP2D6; significant first-pass effect (~50%)
Bioavailability: Oral: ~50%
Half-life elimination: 3-8 hours (dependent on rate of CYP2D6 metabolism)
Excretion: Urine (<5% to 10% as unchanged drug)
Dosage
Children: Hypertension: Oral:
1-17 years: Immediate release tablet: (National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, 2004): Initial: 1-2 mg/kg/day; maximum 6 mg/kg/day (≤200 mg/day); administer in 2 divided doses
≥6 years: Extended release tablet: Initial: 1 mg/kg once daily (maximum initial dose: 50 mg/day). Adjust dose based on patient response (maximum: 2 mg/kg/day or 200 mg/day)
Adults:
Angina: Oral:
Immediate release: Initial: 50 mg twice daily; usual dosage range: 50-200 mg twice daily; maximum: 400 mg/day; increase dose at weekly intervals to desired effect
Extended release: Initial: 100 mg/day (maximum: 400 mg/day)
Atrial fibrillation/flutter (ventricular rate control), supraventricular tachycardia (SVT) (acute treatment; unlabeled use; Antman, 2004; Fuster, 2006; Neumar, 2010): I.V.: 2.5-5 mg every 2-5 minutes (maximum total dose: 15 mg over a 10-15 minute period). Note: Initiate cautiously in patients with concomitant heart failure; avoid in patients with decompensated heart failure.
Maintenance: Oral (immediate release): 25-100 mg twice daily
Heart failure: Oral (extended release): Initial: 25 mg once daily (reduce to 12.5 mg once daily in NYHA class higher than class II); may double dosage every 2 weeks as tolerated (target dose: 200 mg/day)
Hypertension: Oral:
Immediate release: Initial: 50 mg twice daily; effective dosage range: 100-450 mg/day in 2-3 divided doses; increase dose at weekly intervals to desired effect; maximum: 450 mg/day; usual dosage range (JNC 7): 50-100 mg/day
Extended release: Initial: 25-100 mg once daily; increase doses at weekly (or longer) intervals to desired effect; maximum: 400 mg/day; usual dosage range (JNC 7): 50-100 mg/day
Hypertension/ventricular rate control: I.V. (in patients having nonfunctioning GI tract): Initial: 1.25-5 mg every 6-12 hours; titrate initial dose to response. Initially, low doses may be appropriate to establish response; however, although not routine, up to 15 mg administered as frequently as every 3 hours has been employed in patients with refractory tachycardia.
Myocardial infarction:
Acute: I.V.: 5 mg every 2 minutes for 3 doses in early treatment of myocardial infarction; thereafter, give 50 mg orally every 6 hours beginning 15 minutes after last I.V. dose and continue for 48 hours; then administer a maintenance dose of 100 mg twice daily. Note: Do not initiate this regimen in those with signs of heart failure, a low output state, increased risk of cardiogenic shock, or other contraindications (eg, second- or third-degree heart block). If initial I.V. dosing is not tolerated, may give 25-50 mg orally (depending on degree of intolerance) every 6 hours beginning 15 minutes after the last I.V. dose or as soon as clinical condition permits.
Secondary prevention (unlabeled use; Olsson, 1992): Oral: Immediate release: 25-100 mg twice daily; optimize dose based on heart rate and blood pressure; continue indefinitely.
Thyrotoxicosis (unlabeled use): Oral: Immediate release: 25-50 mg every 6 hours; may also consider administering extended release formulation (Bahn, 2011)
Elderly: Hypertension: Initiate at the lower end of the dosage range and titrate to response
Note: Switching dosage forms:
When switching from immediate release metoprolol to extended release, the same total daily dose of metoprolol should be used.
When switching between oral and intravenous dosage forms, equivalent beta-blocking effect is achieved when doses in a 2.5:1 (Oral:I.V.) ratio is used. For example, if the patient is receiving an oral dose of 25 mg twice daily (50 mg/day), this would translate to 5 mg I.V. every 6 hours; consider reducing initial I.V. dose to evaluate patient response.
Dosing adjustment in renal impairment: No adjustment required.
Dosing adjustment in hepatic impairment: Reduced dose may be necessary
Administration: Oral
Extended release tablets may be divided in half; do not crush or chew.
Administration: I.V.
I.V. dose is much smaller than oral dose. When administered acutely for cardiac treatment, monitor ECG and blood pressure; may administer by rapid infusion (I.V. push) over 1 minute. May also be administered by slow infusion (ie, 5-10 mg of metoprolol in 50 mL of fluid) over ~30-60 minutes during less urgent situations (eg, substitution for oral metoprolol).
Administration: I.V. Detail
pH: 7.5
Monitoring Parameters
Acute cardiac treatment: Monitor ECG and blood pressure with I.V. administration; heart rate and blood pressure with oral administration. I.V. use in a nonemergency situation: Necessary monitoring for surgical patients who are unable to take oral beta-blockers (because of prolonged ileus) has not been defined. Some institutions require monitoring of baseline and postinfusion heart rate and blood pressure when a patient's response to beta-blockade has not been characterized (ie, the patient's initial dose or following a change in dose). Consult individual institutional policies and procedures.
Dietary Considerations
Regular tablets should be taken with food. Extended release tablets may be taken without regard to meals.
Patient Education
I.V. use in emergency situations: Patient information is appropriate to patient condition.
Oral: Take pulse daily prior to medication and follow prescriber's instruction about holding medication. Do not skip doses. If you have diabetes, monitor serum sugar closely; drug may alter glucose tolerance or mask signs of hypoglycemia. May cause fatigue, dizziness, postural hypotension, or alteration in sexual performance (reversible). Report unresolved swelling of extremities, respiratory difficulty or new cough, unresolved fatigue, unusual weight gain, unresolved constipation, change in color of urine or stool, unusual bleeding or bruising, or unusual muscle weakness. Patient may notice an empty shell of medicine in toilet.
Geriatric Considerations
Due to alterations in the beta-adrenergic autonomic nervous system, beta-adrenergic blockade may result in less hemodynamic response than seen in younger adults. Studies indicate that despite decreased sensitivity to the chronotropic effects of beta-blockade with age, there appears to be an increased myocardial sensitivity to the negative inotropic effect during stress (ie, exercise). Controlled trials have shown the overall response rate for propranolol to be only 20% to 50% in the elderly populations. Therefore, all beta-adrenergic blocking drugs may result in a decreased response as compared to younger adults.
Anesthesia and Critical Care Concerns/Other Considerations
Evidence-Based Information:
Surgery: The ACCF/AHA 2009 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery recommend beta-blockers be continued in patients undergoing surgery who are receiving beta-blockers to treat ACCF/AHA Class I guideline indications such as angina, symptomatic arrhythmias, or hypertension (Class I recommendation).
The majority of published trials suggest a benefit of perioperative beta-blocker use during noncardiac surgery especially in high-risk patients; however, more recent clinical trials have not shown a benefit to perioperative beta-blockade for noncardiac surgery especially when higher fixed-dose regimens are employed (Juul, 2006; POISE study group, 2008; Yang, 2006). Therefore, the guidelines suggest that perioperative beta-blocker therapy titrated to goal heart rate and blood pressure may be beneficial to patients undergoing intermediate risk (eg, carotid endarterectomy, prostate surgery) or vascular surgeries who have coronary artery disease identified or are at high cardiac risk (Class IIa recommendation). High cardiac risk is defined as having >1 of the following clinical risk factors: History of ischemic heart disease, compensated or prior heart failure, cerebrovascular disease, diabetes mellitus, or renal insufficiency (serum creatinine: >2 mg/dL). The use of beta-blockers is uncertain in patients undergoing intermediate risk or vascular surgery with ≤1 clinical risk factor (Class IIb recommendation). Based on available evidence, beta-blockers should be started days to weeks before elective surgery in selected patients when possible and titrated to adequate heart rate control (eg, between 60-80 beats per minute) while avoiding clinically significant bradycardia and hypotension. Routine administration of high fixed-dose beta blockade without dose titration is not useful and may be harmful to beta-blocker naïve patients undergoing noncardiac surgery.
Cardiovascular Considerations
Atrial Fibrillation: Beta-blocker therapy provides effective rate control in patients with atrial fibrillation.
Chronic Stable Angina: Beta-blockers are effective in the treatment of angina as monotherapy or when combined with nitrates and/or calcium channel blockers. In patients with severe intractable angina requiring negative cardiac chronotropic medications, pacemaker placement has been carried out to maintain heart rate in the setting of large doses of beta-blockers and/or calcium channel blockers. Beta-blockers are ineffective in the treatment of pure vasospastic (Prinzmetal) angina.
Coronary Artery Bypass Graft (CABG) Surgery: In patients undergoing CABG, the use of beta-blockers has consistently demonstrated a reduction in the incidence of postoperative atrial fibrillation (POAF). The 2011 ACCF/AHA CABG guidelines recommend the administration of beta-blockers (not specified) for at least 24 hours prior to CABG in all patients unless a contraindication exists. Beta-blockade should be reinstituted as soon as possible after the surgery and prescribed to all CABG patients who do not have contraindications at the time of hospital discharge. Patients who are at high risk of developing POAF who have contraindications to beta-blockade may receive preoperative amiodarone instead. The use of preoperative beta-blockers has also demonstrated a reduction of in-hospital mortality (especially in patients with and LVEF>30%). Beta-blockers also reduce perioperative myocardial ischemia therefore strengthening the need for perioperative administration. In patients who cannot tolerate oral beta-blockade, the use of I.V. beta-blockers (eg, esmolol, metoprolol) is reasonable (Hillis, 2011).
Heart Failure: Strong evidence supports that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable heart failure (NYHA Class II-III). To date, carvedilol, sustained release metoprolol, and bisoprolol have demonstrated a beneficial effect on morbidity and mortality. It is important that beta-blocker therapy be instituted initially at very low doses with gradual and very careful titration.
Hypertension: Beta-blocker therapy in the treatment of hypertension has been associated with improved cardiovascular outcomes. According to the 2003 JNC-VII guidelines for the treatment of hypertension, most patients with hypertension will require treatment with at least 2 antihypertensives. First-line therapy for hypertension is a diuretic (eg, hydrochlorothiazide or chlorthalidone). When a diuretic cannot be used or when a compelling indication exists that requires the use of other drugs, other types of antihypertensives may be used (eg, ACEIs, ARBs, beta-blockers, CCBs). Beta-blockers are among the multiple choices of agents that have shown benefit in a number of different patient subtypes. Compelling indications for a beta-blocker include patients with heart failure, postmyocardial infarction, high coronary disease risk, or diabetes. In type 2 diabetic patients, a UK Prospective Diabetes Study Group (UKPDS) trial showed that beta-blocker therapy (atenolol) was as effective as an ACE inhibitor in reducing cardiovascular events and that the benefits of therapy were related more to the degree of antihypertensive efficacy rather than the class of drug used.
Treatment should be targeted to a goal blood pressure of <140/90 mm Hg. If diabetes or renal disease coexists, the blood pressure goal should be <130/80 mm Hg.
Neurocardiogenic Syncope: Metoprolol has also been used in the treatment of neurocardiogenic (vasovagal) syncope.
ST-Segment Elevation Myocardial Infarction (STEMI): Beta-blockers, without intrinsic sympathomimetic activity (ISA), have been shown to decrease morbidity and mortality when initiated in the acute treatment of STEMI and continued long-term. Oral beta-blockade should be initiated promptly in patients without contraindications (eg, signs of heart failure, evidence of a low output state, risk of cardiogenic shock, or other beta-blocker contraindications) (Class I recommendation). Use of intravenous beta-blockade may be considered and given promptly if the patient is experiencing concomitant hypertension unless any of the aforementioned contraindications exist (Class IIa recommendation). Patients at risk of cardiogenic shock include patients with age >70 years, systolic blood pressure <120 mm Hg, heart rate >110 bpm or <60 bpm, or late presentation.
Unstable Angina/Non-ST-Segment Elevation MI (UA/NSTEMI): In the treatment of UA/NSTEMI, oral beta-blockade should be initiated within the first 24 hours in patients without contraindications (eg, signs of heart failure, evidence of a low output state, risk of cardiogenic shock, or other beta-blocker contraindications) (Class I recommendation). Use of intravenous beta-blockade should only be considered if the patient is experiencing concomitant hypertension upon presentation (Class IIa recommendation).
Withdrawal: Beta-blocker therapy should not be withdrawn abruptly, but gradually tapered to avoid acute tachycardia and hypertension.
Dental Health: Effects on Dental Treatment
Metoprolol is a cardioselective beta-blocker. Local anesthetic with vasoconstrictor can be safely used in patients medicated with metoprolol. Nonselective beta-blockers (ie, propranolol, nadolol) enhance the pressor response to epinephrine, resulting in hypertension and bradycardia; this has not been reported for metoprolol. Many nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can reduce the hypotensive effect of beta-blockers after 3 or more weeks of therapy with the NSAID. Short-term NSAID use (ie, 3 days) requires no special precautions in patients taking beta-blockers.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Sedation and dizziness are common; may cause depression; may rarely cause insomnia, confusion, amnesia, or nightmares
Mental Health: Effects on Psychiatric Treatment
Barbiturates may decrease the effects of metoprolol; beta-blockers may increase the effects of psychotropics; monitor clinical status for potential changes
Nursing: Physical Assessment/Monitoring
Monitor blood pressure and cardiac status. Assess for fluid balance, heart failure symptoms, and postural hypotension. Taper dosage slowly when discontinuing. Report abdominal pain, unusual bleeding or bruising, or changes in color of urine or stool. Advise patients with diabetes to monitor glucose levels closely; beta-blockers may alter glucose tolerance.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, solution, as tartrate: 1 mg/mL (5 mL)
Lopressor®: 1 mg/mL (5 mL)
Injection, solution, as tartrate [preservative free]: 1 mg/mL (5 mL)
Tablet, oral, as tartrate: 25 mg, 50 mg, 100 mg
Lopressor®: 50 mg, 100 mg [scored]
Tablet, extended release, oral, as succinate: 25 mg [expressed as mg equivalent to tartrate], 50 mg [expressed as mg equivalent to tartrate], 100 mg [expressed as mg equivalent to tartrate], 200 mg [expressed as mg equivalent to tartrate]
Toprol-XL®: 25 mg, 50 mg, 100 mg, 200 mg [scored; expressed as mg equivalent to tartrate]
Pricing: U.S. (www.drugstore.com)
Tablet, 24-hour (Metoprolol Succinate)
25 mg (30): $29.99
50 mg (30): $33.99
100 mg (30): $44.99
200 mg (90): $195.99
Tablet, 24-hour (Toprol XL)
25 mg (30): $46.99
50 mg (30): $44.99
100 mg (30): $60.99
200 mg (90): $266.98
Tablets (Lopressor)
50 mg (60): $118.99
100 mg (60): $165.98
Tablets (Metoprolol Tartrate)
25 mg (30): $12.99
50 mg (60): $13.99
100 mg (60): $15.99
Extemporaneously Prepared
A 10 mg/mL oral suspension may be made with metoprolol tartrate tablets and one of three different vehicles (cherry syrup; a 1:1 mixture of Ora-Sweet® and Ora-Plus®; or a 1:1 mixture of Ora-Sweet® SF and Ora-Plus®). Crush twelve 100 mg tablets in a mortar and reduce to a fine powder. Add 20 mL of the chosen vehicle and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label "shake well" and "protect from light". Stable for 60 days.
Allen LV Jr and Erickson MA 3rd, "Stability of Labetalol Hydrochloride, Metoprolol Tartrate, Verapamil Hydrochloride, and Spironolactone With Hydrochlorothiazide in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1996, 53(19):2304-9.
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International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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