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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.
Medication Safety Issues
Sound-alike/look-alike issues:
Lopressor® may be confused with Lyrica®
Metoprolol may be confused with metaproterenol, metoclopramide, metolazone, misoprostol
Toprol-XL® may be confused with Tegretol®, Tegretol®-XR, Topamax®
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Significant differences exist between oral and I.V. dosing. Use caution when converting from one route of administration to another.
Pronunciation
(me toe PROE lole)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
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/Investigational
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
Pregnancy Risk Factor
C (manufacturer); D (2nd and 3rd trimesters - expert analysis)
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. Metoprolol crosses the placenta. Maternal use of beta-blockers has been associated with fetal bradycardia, hypotension, and IUGR; IUGR is probably related to maternal hypertension. Available evidence suggests beta-blockers are generally safe during pregnancy (JNC 7). Cases of neonatal hypoglycemia have been reported following maternal use of beta-blockers at parturition. Information specific to metoprolol is limited.
Lactation
Enters breast milk/use caution (AAP rates “compatible”)
Breast-Feeding Considerations
Metoprolol is considered compatible by the AAP. However, monitor the infant for signs of beta-blockade (hypotension, bradycardia, etc) with long-term use.
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): Use with caution in patients with PVD (including Raynaud's).
• 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.
• Thyrotoxicosis: Beta-blockade may mask signs of hyperthyroidism (eg, tachycardia). Abrupt discontinuation of beta-blockade may exacerbate symptoms of hyperthyroidism and may also induce thyroid storm.
Concurrent drug therapy issues:
• Anesthetic agents: Use with caution in patients receiving inhalation anesthetic agents which may decrease myocardial function.
• 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.
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.
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
Miscellaneous: Cold extremities (1%)
Postmarketing and/or case reports: Agranulocytosis, alkaline phosphatase increased, alopecia (reversible), arthralgia, arthritis, anxiety, 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), 2D6 (major); Inhibits CYP2D6 (weak)
Drug Interactions
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 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
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
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. Risk C: Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. 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
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 decrease the metabolism of Lidocaine. Risk C: Monitor therapy
MAO Inhibitors: May enhance the orthostatic effect of Orthostasis Producing Agents. 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
Propoxyphene: May decrease the metabolism of Beta-Blockers. 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 enhance the bradycardic effect of Beta-Blockers. Exceptions: 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. This is true at higher beta-blockers doses where cardioselectivity is lost. 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.
Herb/Nutraceutical: Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (American), gotu kola, licorice, (may worsen hypertension). Avoid black cohosh, California poppy, coleus, golden seal, hawthorn, mistletoe, periwinkle, quinine, shepherd's purse (may have increased antihypertensive effect).
Storage
Injection: Store at controlled room temperature of 25°C (77°F). Protect from light.
Tablet: Store at controlled room temperature of 25°C (77°F). Protect from moisture.
Compatibility
Stable in D5W, NS.
Y-site administration: Compatible: Alteplase, meperidine, morphine. Incompatible: Amphotericin B cholesteryl sulfate complex.
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 (ventricular rate control), supraventricular tachycardia (SVT) (acute treatment; unlabeled use; Antman, 2004; Fuster, 2006): 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
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 (maximum: 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, up to 15 mg every 3-6 hours has been employed.
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: 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.
Elderly: Initiate at the lower end of the dosage range
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. Necessary monitoring for surgical patients who are unable to take oral beta-blockers (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: Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed. Do not change dosage or discontinue without consulting prescriber. Take pulse daily, prior to medication and follow prescriber's instruction about holding medication. Do not take with antacids. If you have diabetes, monitor blood glucose closely (drug may alter glucose tolerance or mask signs of hypoglycemia). May cause fatigue, dizziness, or postural hypotension (use caution when changing position from lying or sitting to standing, when driving, or when climbing stairs until response to medication is known); or alteration in sexual performance (reversible). Report unresolved swelling of extremities, respiratory difficulty or new cough, unresolved fatigue, unusual weight gain, unresolved constipation, or unusual muscle weakness. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
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
Clinical Pearls/Comments:
Surgery: Based on available evidence, beta-blockers should be started days to weeks before elective surgery in selected patients when possible and titrated to a heart rate <65 beats per minute. Additional data suggest that long acting beta-blockers may be superior to short acting ones (Redelmeier, 2005). The ACC/AHA 2007 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 angina, symptomatic arrhythmias, hypertension, or other ACC/AHA Class I guideline indications (Class I recommendation). The guidelines also recommend that beta-blockers be given to patients undergoing vascular surgery who have myocardial ischemia demonstrated during preoperative testing (Class I recommendation).
The guidelines also state that beta-blockers are probably recommended in patients undergoing intermediate risk (eg, carotid endarterectomy, prostate surgery) or vascular surgery in whom preoperative assessment identifies coronary heart disease or 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. The use of beta-blockers is uncertain in patients undergoing intermediate risk or vascular surgery with ?1 clinical risk factor (Class IIb recommendation).
The majority of published trials suggest a benefit of perioperative beta-blocker use during noncardiac surgery; however, more recent clinical trials have not shown a benefit to perioperative beta-blockade for noncardiac surgery (Juul, 2006; POISE Study Group, 2008; Yang, 2006). One such clinical trial randomized 8351 patients with, or at risk of, atherosclerotic disease who underwent noncardiac surgery to either extended release metoprolol succinate or placebo. To receive study drug, first dose (metoprolol extended release 100 mg or matching placebo) administered 2-4 hours prior to surgery, patients were to have a heart rate ?50 bpm or systolic blood pressure (SBP) ?100 mm Hg. If during the first 6 hours after surgery heart rate was ?80 bpm and SBP ?100 mm Hg, the first postoperative dose (metoprolol extended release 100 mg or matching placebo) was administered. If not given during the first 6 hours, metoprolol extended release 100 mg (or matching placebo) was administered at 6 hours after surgery. Twelve hours after administration of the first postoperative dose, metoprolol extended release 200 mg (or matching placebo) was administered once daily for 30 days. Therefore, patients may have received up to 400 mg during the first 24 hours; an initial dose not recommended for any indication. Study drug was withheld when heart rate was consistently <45 bpm or systolic blood pressure was <100 mm Hg. The primary outcome of the trial was a composite of cardiovascular death, nonfatal MI, and nonfatal cardiac arrest at 30 days after randomization. Compared to those who received placebo, fewer patients receiving metoprolol experienced the primary outcome (244 [5.8%] vs 290 [6.9%], p=0.0399) or developed MI (176 [4.2%] vs 239 [5.7%], p=0.0017). However, more deaths occurred in the metoprolol group compared to placebo (129 [3.1%] vs 97 [2.3%], p=0.0317). In addition, more strokes occurred in the metoprolol group compared to placebo (41 [1%] vs 19 [0.5%], p=0.0053). Death was associated with a number of risk factors (eg, clinically significant hypotension, MI, significant bleeding). Stroke was associated with history of stroke or TIA, postoperative hypotension, new-onset atrial fibrillation, and significant bleeding (POISE Study Group, 2008). The negative results of this trial are thought to be due to the aggressive administration of metoprolol leading to an excessive amount of clinically significant hypotension which then contributed to the incidence of stroke and mortality. Therefore, when administering beta-blockers to eligible patients undergoing elective surgery, patients should be titrated days to weeks in advance when possible and careful monitoring of heart rate (goal <65 bpm) and blood pressure is necessary.
Extemporaneously Prepared: To prepare a metoprolol 10 mg/mL liquid, crush 12 metoprolol tartrate 100 mg tablets into a fine powder. Add ~20 mL of either Ora-Sweet® and Ora-Plus® (1:1 preparation), or Ora-Sweet® SF and Ora-Plus® (1:1 preparation), or cherry syrup. Mix to a uniform paste. Continue to add the vehicle to bring the final volume to 120 mL. The preparation is stable for 60 days; shake well before using and protect from light.
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.
Heart Failure: Strong evidence supports that beta-blocker therapy, without intrinsic sympathomimetic activity (ISA), should be initiated in select patients with stable congestive 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
Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking. I.V.: See Administration specifics and monitor blood pressure and cardiac status. Assess therapeutic effectiveness and adverse reactions (eg, fluid balance, CHF, postural hypotension). Caution patients with diabetes to monitor serum glucose closely; may decrease the effect of sulfonylureas and can mask prominent hypoglycemic symptoms. Teach patient proper use (oral), possible side effects/appropriate interventions, and adverse symptoms to report.
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)
Tablet, as tartrate: 25 mg, 50 mg, 100 mg
Lopressor®: 50 mg, 100 mg
Tablet, extended release, as succinate: 25 mg, 50 mg, 100 mg, 200 mg [expressed as mg equivalent to tartrate]
Toprol-XL®: 25 mg, 50 mg, 100 mg, 200 mg [expressed as mg equivalent to tartrate]
Pricing: U.S. (www.drugstore.com)
Tablet, 24-hour (Metoprolol Succinate)
25 mg (30): $30.99
50 mg (30): $33.88
100 mg (30): $41.99
200 mg (90): $204.58
Tablet, 24-hour (Toprol XL)
25 mg (30): $39.99
50 mg (30): $39.99
100 mg (30): $54.99
200 mg (90): $243.06
Tablets (Lopressor)
50 mg (60): $100.00
100 mg (60): $136.19
Tablets (Metoprolol Tartrate)
25 mg (30): $12.99
50 mg (60): $12.99
100 mg (60): $15.99
Extemporaneously Prepared
To prepare a metoprolol 10 mg/mL liquid, crush 12 metoprolol tartrate 100 mg tablets into a fine powder. Add ~20 mL of either Ora-Sweet® and Ora-Plus® (1:1 preparation), or Ora-Sweet® SF and Ora-Plus® (1:1 preparation), or cherry syrup. Mix to a uniform paste. Continue to add the vehicle to bring the final volume to 120 mL. The preparation is stable for 60 days; shake well before using and protect from light.
Allen LV and Erickson III MA, “Stability of Labetalol Hydrochloride, Metoprolol Tartrate, Verapamil Hydrochloride, and Spironolactone With Hydrochlorothiazide in Extemporaneously Compounded Oral Liquids,” Am J Health Syst Pharm, 1996, 53:2304-9.
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International Brand Names
Lexi-Comp.com
Last full review/revision November 2009
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