(me toe PROE lole)
- Metoprolol Succinate
- Metoprolol Tartrate
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous, as tartrate:
Lopressor: 1 mg/mL (5 mL [DSC])
Generic: 1 mg/mL (5 mL); 5 mg/5 mL (5 mL)
Tablet, Oral, as tartrate:
Lopressor: 50 mg, 100 mg [scored]
Lopressor: 100 mg [scored; contains fd&c blue #2 aluminum lake]
Generic: 25 mg, 37.5 mg, 50 mg, 75 mg, 100 mg
Tablet Extended Release 24 Hour, Oral, as succinate:
Toprol XL: 25 mg, 50 mg, 100 mg, 200 mg [scored]
Generic: 25 mg, 50 mg, 100 mg, 200 mg
Brand Names: U.S.
- Toprol XL
- Antianginal Agent
- Beta-Blocker, Beta-1 Selective
Selective inhibitor of beta1-adrenergic receptors; competitively blocks beta1-receptors, with little or no effect on beta2-receptors at oral doses <100 mg (in adults); does not exhibit any membrane stabilizing or intrinsic sympathomimetic activity
Rapid and complete
Vd: 3.2 to 5.6 L/kg; crosses the blood brain barrier; CSF concentrations are 78% of plasma concentrations
Extensively hepatic via CYP2D6; significant first-pass effect (~50%)
Urine (95%, <5% to 10% as unchanged drug; increased to 30% to 40% in poor CYP2D6 metabolizers)
Onset of Action
Oral: Immediate release tablets: Within 1 hour; Peak effect: Oral: 1 to 2 hours (Regårdh 1980); IV: 20 minutes (when infused over 10 minutes)
Duration of Action
Oral: Immediate release: Variable (dose-related; 50% reduction in maximum heart rate after single doses of 20, 50, and 100 mg occurred at 3.3, 5, and 6.4 hours, respectively), Extended release: ~24 hours
Neonates: 5 to 10 hours (Morselli 1989); Adults: 3 to 4 hours (7 to 9 hours in poor CYP2D6 metabolizers or hepatic impairment)
~10% to 12% to albumin
Special Populations: Hepatic Function Impairment
Elimination half-life may be considerably prolonged, depending on severity.
Special Populations: Race
Poor CYP2D6 metabolizers (~8% Caucasians; ~2% other populations) have several-fold higher metoprolol plasma concentrations.
Use: Labeled Indications
Angina (oral formulations): Long term treatment of angina pectoris.
Heart failure (extended-release oral formulation): Treatment of stable, symptomatic (NYHA Class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin to reduce the rate of mortality plus hospitalization in patients already receiving ACE inhibitors, diuretics, and/or digoxin.
Hypertension (oral formulations): Management of hypertension.
Myocardial infarction (immediate-release oral formulation; injection): Treatment of hemodynamically stable acute myocardial infarction (MI) to reduce cardiovascular mortality (injection to be used in combination with metoprolol oral maintenance therapy).
Acute coronary syndromes (eg, myocardial infarction, unstable angina): According to the ACCF/AHA 2013 guidelines for the management of ST-elevation myocardial infarction (STEMI) and the guidelines for the management of unstable angina/non-STEMI, oral beta-blockers should be initiated within the first 24 hours unless the patient has signs of heart failure, evidence of a low-output state, an increased risk for cardiogenic shock, or other contraindications. Intravenous use should be reserved for those patients who have refractory hypertension or ongoing ischemia (ACCF/AHA [Anderson 2013]; ACCF/AHA [O’Gara 2013]).
Heart failure: The ACCF/AHA 2013 heart failure guidelines recommend the use of 1 of 3 beta blockers (ie, bisoprolol, carvedilol, or extended-release metoprolol succinate) for all patients with recent or remote history of MI or ACS and reduced ejection fraction (rEF) to reduce mortality, for all patients with rEF to prevent symptomatic HF (even if no history of MI), and for all patients with current or prior symptoms of HF with reduced ejection fraction (HFrEF), unless contraindicated, to reduce morbidity and mortality (ACCF/AHA [Yancy 2013]).
Hypertension: The 2014 guideline for the management of high blood pressure in adults (Eighth Joint National Committee [JNC 8]) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients (JNC8 [James 2013]):
• Patients ≥60 years of age, with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.
• Patients <60 years of age, with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
• Patients ≥18 years of age with diabetes, with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
• Patients ≥18 years of age with chronic kidney disease (CKD), with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
Chronic kidney disease (CKD) and hypertension: Regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general nonblack population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB.
Coronary artery disease (CAD) and hypertension: The American Heart Association, American College of Cardiology and American Society of Hypertension (AHA/ACC/ASH) 2015 scientific statement for the treatment of hypertension in patients with coronary artery disease (CAD) recommends the use of a beta blocker as part of a regimen in patients with hypertension and chronic stable angina with a history of prior MI. A BP target of <140/90 mm Hg is reasonable for the secondary prevention of cardiovascular events. A lower target BP (<130/80 mm Hg) may be appropriate in some individuals with CAD, previous MI, stroke or transient ischemic attack, or CAD risk equivalents (AHA/ACC/ASH [Rosendorff 2015]).
Treatment of ventricular arrhythmias, atrial ectopy; migraine prophylaxis, essential tremor; 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
Hypersensitivity to metoprolol, any component of the formulation, or other beta-blockers; second- or third-degree heart block.
Note: Additional contraindications are formulation and/or indication specific.
Immediate-release tablets/injectable formulation:
Hypertension and angina (oral only): Sinus bradycardia; cardiogenic shock; overt heart failure; sick sinus syndrome; severe peripheral arterial circulatory disorders
Myocardial infarction (oral and injection): Severe sinus bradycardia (heart rate <45 beats/minute); significant first-degree heart block (P-R interval ≥0.24 seconds); systolic blood pressure <100 mm Hg; moderate to severe cardiac failure
Extended-release tablet: Severe bradycardia, cardiogenic shock; decompensated heart failure; sick sinus syndrome (except in patients with a functioning artificial pacemaker)
Immediate release (metoprolol tartrate): Initial: 50 mg twice daily; usual dosage range: 50 to 200 mg twice daily; may increase dose at weekly intervals to desired effect (maximum: 400 mg/day).
Extended release (metoprolol succinate): Initial: 100 mg once daily; may increase dose at weekly intervals to desired effect (maximum: 400 mg/day).
Atrial fibrillation/flutter (ventricular rate control), supraventricular tachycardia (SVT) (acute treatment; off-label use; AHA/ACC/HRS [January 2014]; AHA [Neumar 2010]): IV: 2.5 to 5 mg every 2 to 5 minutes (maximum total dose: 15 mg over a 10- to 15-minute period). Note: Initiate cautiously in patients with concomitant heart failure. Avoid in patients with decompensated heart failure; electrical cardioversion preferred.
Maintenance: Oral (immediate release [metoprolol tartrate]): 25 to 100 mg twice daily; Oral (extended release [metoprolol succinate]): 50 to 400 mg once daily
Heart failure: Note: Initiate only in stable patients or hospitalized patients after volume status has been optimized and IV diuretics, vasodilators, and inotropic agents have all been successfully discontinued. Caution should be used when initiating in patients who required inotropes during their hospital course. Increase dose gradually and monitor for congestive signs and symptoms of HF making every effort to achieve target dose shown to be effective (ACCF/AHA [Yancy 2013]; HFSA [Lindenfeld 2010]; MERIT-HF Study Group 1999).
Oral: Extended release (metoprolol succinate): 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 up to target dose of 200 mg/day.
ACCF/AHA 2013 Heart Failure Guidelines: Oral (extended release [metoprolol succinate]): Initial: 12.5 to 25 mg once daily; maximum dose: 200 mg/day (Yancy 2013).
Immediate release (metoprolol tartrate): Initial: 50 mg twice daily; effective dosage range: 100 to 450 mg daily in 2 to 3 divided doses; may increase dose at weekly (or longer) intervals to desired effect; maximum dose: 450 mg/day; usual dosage range (ASH/ISH [Weber 2014]): 50 to 100 mg twice daily; target dose (JNC 8 [James 2013]): 100 to 200 mg daily
Extended release (metoprolol succinate): Initial: 25 to 100 mg once daily; may increase dose at weekly (or longer) intervals to desired effect; maximum: 400 mg/day.
Hypertension/ventricular rate control: IV (in patients having nonfunctioning GI tract): Initial: 1.25 to 5 mg every 6 to 12 hours; titrate initial dose to response. Initially, low doses may be appropriate to establish response (Huckleberry 2003); however, although not routine, up to 15 mg administered as frequently as every 3 hours has been employed in patients with refractory tachycardia.
Early treatment: Note: The ACCF/AHA guidelines for the management of STEMI recommend the use of IV metoprolol at the time of presentation only in patients with STEMI who are hypertensive or have ongoing ischemia without contraindications. Oral metoprolol (immediate release) initiated within the first 24 hours is recommended in all other patients. Do not initiate metoprolol 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) (ACCF/AHA [O'Gara 2013]).
IV: 5 mg every 5 minutes as tolerated for up to 3 doses in the early treatment of ST elevation myocardial infarction; titrate to heart rate and blood pressure; then begin oral therapy (ACCF/AHA [O'Gara 2013]).
Oral: 25 to 50 mg (metoprolol tartrate [immediate release]) every 6 to 12 hours; transition over the next 2 to 3 days to twice daily dosing of metoprolol tartrate (immediate release) or to daily metoprolol succinate (extended release) and increase as tolerated to a maximum dose of 200 mg/day (ACCF/AHA [O'Gara 2013]).
Secondary prevention (off-label use): Oral: Immediate release (metoprolol tartrate): 25 to 100 mg twice daily; optimize dose based on heart rate and blood pressure; continue indefinitely (Olsson 1992).
Thyrotoxicosis (off-label use): Oral: Immediate release (metoprolol tartrate): 25 to 50 mg every 6 hours; may also consider administering extended-release formulation (metoprolol succinate) (Bahn 2011).
Note: Switching dosage forms:
When switching from immediate release (metoprolol tartrate) to extended release (metoprolol succinate), the same total daily dose of metoprolol should be used.
When switching between oral and intravenous dosage forms, in most cases, equivalent beta-blocking effect is achieved when doses in a 2.5:1 (Oral:IV) ratio is used. However, in one bioavailability study including healthy volunteers, a range of Oral:IV conversion ratios was found to be approximately 2:1 to 5:1 (Regardh 1974). Therefore, patient variability may exist and a specific ratio may not apply to all patients, especially if comorbid conditions are present. For example, based on a range of 2.5:1 to 5:1 ratios, if the patient is receiving a chronic oral dose of 25 mg twice daily (50 mg daily), this would translate to 2.5 to 5 mg IV every 6 hours. Recognizing that patients receiving larger chronic oral doses should not automatically be converted to a large IV dose, consideration should be given to further reducing the initial IV dose and basing subsequent doses on the clinical response (Huckleberry 2003).
Refer to adult dosing. In the management of hypertension, consider lower initial doses and titrate to response (Aronow 2011).
Immediate-release tablet (metoprolol tartrate): Children ≥1 year and Adolescents ≤17 years (off-label population): Initial: 0.5 to 1 mg/kg/dose (maximum initial dose: 25 mg/dose) twice daily. Adjust dose based on patient response; maximum daily dose: 6 mg/kg/day or 200 mg/day, whichever is less (NHLBI 2011; NHBPEP 2004).
Extended-release tablet (metoprolol succinate): Children ≥6 years and Adolescents: Initial: 1 mg/kg once daily (maximum initial dose: 50 mg/dose). Adjust dose based on patient response (maximum: 2 mg/kg/day or 200 mg/day, whichever is less)
Dosing: Renal Impairment
No dosage adjustment necessary.
Dosing: Hepatic Impairment
There are no specific dosage adjustments provided in the manufacturer's labeling. Consider initiating with reduced doses and gradual dosage titration due to extensive hepatic metabolism.
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):2304-9.8893069
Immediate release (metoprolol tartrate): Administer with or immediately following food (Melander 1977).
Extended release (metoprolol succinate): Administer without regard to meals (Tangeman 2003; van den Berg 1990; Wikstrand 2003). May divide tablets in half; do not crush or chew.
IV: When administered acutely for cardiac treatment, monitor ECG and blood pressure. Administer by IV bolus. Some centers may administer by slow infusion (ie, 5 to 10 mg of metoprolol in 50 mL of fluid) over ~30 to 60 minutes during less urgent situations (eg, substitution for oral metoprolol).
Immediate-release tablets should be taken with or immediately following food (Melander 1977).
Stable in D5W, NS.
Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex, lidocaine, nitroglycerin.
Injection: Store at 20°C to 25°C (68°F to 77°F). Do not freeze; 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.
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. Consider therapy modification
Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Ajmaline: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. 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. 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. Monitor therapy
Alpha2-Agonists: May enhance the AV-blocking effect of Beta-Blockers. Sinus node dysfunction may also be enhanced. Beta-Blockers may enhance the rebound hypertensive effect of Alpha2-Agonists. This effect can occur when the Alpha2-Agonist is abruptly withdrawn. Management: Closely monitor heart rate during treatment with a beta blocker and clonidine. Withdraw beta blockers several days before clonidine withdrawal when possible, and monitor blood pressure closely. Recommendations for other alpha2-agonists are unavailable. Exceptions: Apraclonidine. Consider therapy modification
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Aminoquinolines (Antimalarial): May decrease the metabolism of Beta-Blockers. 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. Monitor therapy
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Anilidopiperidine Opioids: May enhance the bradycardic effect of Beta-Blockers. Anilidopiperidine Opioids may enhance the hypotensive effect of Beta-Blockers. 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. Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification
Barbiturates: May decrease the serum concentration of Beta-Blockers. Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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. Monitor therapy
Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy
Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. 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. Monitor therapy
Cardiac Glycosides: Beta-Blockers may enhance the bradycardic effect of Cardiac Glycosides. Monitor therapy
Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Avoid combination
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. Monitor therapy
Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors: May increase the serum concentration of Metoprolol. Management: Consider an alternative for one of the interacting drugs in order to avoid metoprolol toxicity. If the combination must be used, monitor response to metoprolol closely. Metoprolol dose reductions may be necessary. Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Dipyridamole: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Disopyramide: May enhance the bradycardic effect of Beta-Blockers. Beta-Blockers may enhance the negative inotropic effect of Disopyramide. 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. Consider therapy modification
Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Consider therapy modification
Fingolimod: Beta-Blockers may enhance the bradycardic effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and beta-blockers if possible. If coadministration is necessary, patients should have overnight continuous ECG monitoring conducted after the first dose of fingolimod. Monitor patients for bradycardia. Consider therapy modification
Floctafenine: May enhance the adverse/toxic effect of Beta-Blockers. Avoid combination
Grass Pollen Allergen Extract (5 Grass Extract): Beta-Blockers may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). More specifically, Beta-Blockers may inhibit the ability to effectively treat severe allergic reactions to Grass Pollen Allergen Extract (5 Grass Extract) with epinephrine. Some other effects of epinephrine may be unaffected or even enhanced (e.g., vasoconstriction) during treatment with Beta-Blockers. Consider therapy modification
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Insulin: Beta-Blockers may enhance the hypoglycemic effect of Insulin. Monitor therapy
Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy
Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy
Lercanidipine: May enhance the hypotensive effect of Metoprolol. Metoprolol may decrease the serum concentration of Lercanidipine. Monitor therapy
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Lidocaine (Systemic): Beta-Blockers may increase the serum concentration of Lidocaine (Systemic). Monitor therapy
Lidocaine (Topical): Beta-Blockers may increase the serum concentration of Lidocaine (Topical). Monitor therapy
Mepivacaine: Beta-Blockers may increase the serum concentration of Mepivacaine. Monitor therapy
Methacholine: Beta-Blockers may enhance the adverse/toxic effect of Methacholine. Avoid combination
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Midodrine: Beta-Blockers may enhance the bradycardic effect of Midodrine. Monitor therapy
Mirabegron: May diminish the antihypertensive effect of Metoprolol. Mirabegron may increase the serum concentration of Metoprolol. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
NIFEdipine: May enhance the hypotensive effect of Beta-Blockers. NIFEdipine may enhance the negative inotropic effect of Beta-Blockers. Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: May diminish the antihypertensive effect of Beta-Blockers. Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification
Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Propafenone: May increase the serum concentration of Beta-Blockers. Propafenone possesses some independent beta blocking activity. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Regorafenib: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy
Reserpine: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy
Rifamycin Derivatives: May decrease the serum concentration of Beta-Blockers. Exceptions: Rifabutin. Monitor therapy
Rivastigmine: May enhance the bradycardic effect of Beta-Blockers. Avoid combination
Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy
Selective Serotonin Reuptake Inhibitors: May increase the serum concentration of Beta-Blockers. Exceptions: Citalopram; Escitalopram; FluvoxaMINE. 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. 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. Monitor therapy
Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Frequency not always defined.
Cardiovascular: Hypotension (1% to 27%), bradycardia (2% to 16%), first degree atrioventricular block (5%), arterial insufficiency (usually Raynaud type: 1%), cardiac failure (1%), cerebrovascular accident (1%), cold extremities (1%), palpitations (1%), peripheral edema (1%), claudication
Central nervous system: Dizziness (2% to 10%), fatigue (1% to 10%), depression (>2% to 5%), vertigo (≤2%), confusion, disturbed sleep, hallucination, headache, insomnia, nightmares, temporary amnesia
Dermatology: Pruritus (5%), rash (>2% to 5%), exacerbation of psoriasis, skin photosensitivity
Endocrine & metabolic: Decreased libido, unstable diabetes
Gastrointestinal: Diarrhea (>2% to 5%), constipation (1%), flatulence (1%), heartburn (1%), stomach pain (1%), xerostomia (1%), nausea (≤1%), vomiting
Neuromuscular & skeletal: Musculoskeletal pain
Ophthalmic: Blurred vision, visual disturbance
Respiratory: Dyspnea (≤3%), bronchospasm (1%), wheezing (1%), rhinitis
Miscellaneous: Accidental injury (1%)
<1% (Limited to important or life-threatening): Abdominal pain, agranulocytosis, alopecia (reversible), anxiety, arthralgia, arthritis, chest pain, decreased HDL cholesterol, diaphoresis, drowsiness, dry eye syndrome, gangrene, hepatic insufficiency, hepatitis, impotence, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum transaminases, increased serum triglycerides, jaundice, nervousness, paresthesia, Peyronie’s disease, retroperitoneal fibrosis, syncope, taste disorder, weight gain
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. Metoprolol may also produce severe first-, 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.
• Bradycardia: Bradycardia, including sinus pause, heart block, and cardiac arrest, may occur. Patients with first-degree AV block, sinus node dysfunction, or conduction disorders may be at increased risk. Monitor heart rate and rhythm; if severe bradycardia occurs, reduce dose or discontinue therapy.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).
• Hypotension: Symptomatic hypotension may occur with use.
• 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 preexisting 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 ER formulation is indicated for use in heart failure). May need to increase diuretics and wait until clinically stable to advance dose to target.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Myasthenia gravis: Use beta-blockers with caution in patients with myasthenia gravis.
• Peripheral vascular disease (PVD) and Raynaud disease: May precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud 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.
• Prinzmetal variant angina: Beta-blockers without alpha1-adrenergic receptor blocking activity should be avoided in patients with Prinzmetal variant angina because unopposed alpha1-adrenergic receptors mediate coronary vasoconstriction and can worsen anginal symptoms (Mayer 1998).
• 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 beta-blockers 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:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
• Elderly: Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary.
• Abrupt withdrawal: [US Boxed Warning]: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered over 1 to 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, avoid initiation of high-dose ER metoprolol in patients undergoing noncardiac surgery; use in patients with cardiovascular risk factors has been associated with bradycardia, hypotension, stroke, and death. Chronic beta-blocker therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
Acute cardiac treatment: Monitor ECG, heart rate, and blood pressure with IV administration; heart rate, rhythm, and blood pressure with oral administration.
IV 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.
Pregnancy Risk Factor
Adverse events have been observed in animal reproduction studies. Metoprolol and the metabolite alpha-hydroxymetoprolol cross the placenta and can be detected in cord blood (Lindeberg 1987; Ryu 2015).
Adverse events, such as fetal/neonatal bradycardia, hypoglycemia, and reduced birth weight, have been observed following in utero exposure to beta-blockers as a class. Adequate facilities for monitoring infants at birth is generally recommended. The pharmacokinetics of metoprolol may be changed during pregnancy; the degree of changes may be dependent upon maternal CYP2D6 genotype (Ryu 2015).
Untreated chronic maternal hypertension and preeclampsia are also associated with adverse events in the fetus, infant, and mother (ACOG 2015; Magee 2014). Recommendations for the treatment of hypertension in pregnancy vary by guideline, but use of metoprolol may be considered (Magee 2014; Regitz-Zagrosek 2011). Metoprolol is recommended for the treatment of heart failure in pregnant women when use of a beta-blocker is indicated (Regitz-Zagrosek 2011; Sliwa 2010) and may also be used in other cardiovascular-related diseases of pregnancy (Regitz-Zagrosek 2011). Use of metoprolol may be considered if migraine prophylaxis is needed in a pregnant woman (Pringsheim 2012).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience diarrhea, loss of strength and energy, or vomiting. Have patient report immediately to prescriber depression, illogical thinking, memory impairment, severe dizziness, passing out, skin discoloration, sensation of cold, angina, arrhythmia, bradycardia, shortness of breath, excessive weight gain, swelling of arms or legs, or vision changes (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about metoprolol
- Metoprolol Succinate (AHFS Monograph)
- Metoprolol (FDA)
- Metoprolol Succinate (FDA)
- Metoprolol Tartrate Injection (FDA)
- Metoprolol Tartrate Tablet (FDA)