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Metoprolol (Monograph)

Brand names: Toprol XL, Lopressor
Drug class: alpha-Adrenergic Blocking Agents

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

β1-Selective adrenergic blocking agent (β-blocker).109 147

Uses for Metoprolol

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).109 157 161 501 1200

β-Blockers generally not preferred for first-line therapy of hypertension according to current evidence-based hypertension guidelines, but may be considered in patients who have a compelling indication (e.g., prior MI, ischemic heart disease, heart failure) for their use or as add-on therapy in those who do not respond adequately to the preferred drug classes (ACE inhibitors, angiotensin II receptor antagonists, calcium-channel blockers, or thiazide diuretics).242 501 502 503 504 515 523 524 527 1200 Metoprolol succinate and metoprolol tartrate are two of several β-blockers (including bisoprolol, carvedilol, nadolol, propranolol, and timolol) recommended by a 2017 ACC/AHA multidisciplinary hypertension guideline as first-line therapy for hypertension in patients with stable ischemic heart disease/angina.1200

Individualize choice of therapy; consider patient characteristics (e.g., age, ethnicity/race, comorbidities, cardiovascular risk) as well as drug-related factors (e.g., ease of administration, availability, adverse effects, cost).501 502 503 504 515 1200 1201

The 2017 ACC/AHA hypertension guideline classifies BP in adults into 4 categories: normal, elevated, stage 1 hypertension, and stage 2 hypertension.1200 (See Table 1.)

Source: Whelton PK, Carey RM, Aronow WS et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13-115.

Individuals with SBP and DBP in 2 different categories (e.g., elevated SBP and normal DBP) should be designated as being in the higher BP category (i.e., elevated BP).

Table 1. ACC/AHA BP Classification in Adults1200

Category

SBP (mm Hg)

DBP (mm Hg)

Normal

<120

and

<80

Elevated

120–129

and

<80

Hypertension, Stage 1

130–139

or

80–89

Hypertension, Stage 2

≥140

or

≥90

The goal of hypertension management and prevention is to achieve and maintain optimal control of BP.1200 However, the BP thresholds used to define hypertension, the optimum BP threshold at which to initiate antihypertensive drug therapy, and the ideal target BP values remain controversial.501 503 504 505 506 507 508 515 523 526 530 1200 1201 1207 1209 1222 1223 1229

The 2017 ACC/AHA hypertension guideline generally recommends a target BP goal (i.e., BP to achieve with drug therapy and/or nonpharmacologic intervention) <130/80 mm Hg in all adults regardless of comorbidities or level of atherosclerotic cardiovascular disease (ASCVD) risk.1200 In addition, an SBP goal of <130 mm Hg generally is recommended for noninstitutionalized ambulatory patients ≥65 years of age with an average SBP of ≥130 mm Hg.1200 These BP goals are based upon clinical studies demonstrating continuing reduction of cardiovascular risk at progressively lower levels of SBP.1200 1202 1210

Other hypertension guidelines generally have based target BP goals on age and comorbidities.501 504 536 Guidelines such as those issued by the JNC 8 expert panel generally have targeted a BP goal of <140/90 mm Hg regardless of cardiovascular risk and have used higher BP thresholds and target BPs in elderly patients501 504 compared with those recommended by the 2017 ACC/AHA hypertension guideline.1200

Some clinicians continue to support previous target BPs recommended by JNC 8 due to concerns about the lack of generalizability of data from some clinical trials (e.g., SPRINT study) used to support the 2017 ACC/AHA hypertension guideline and potential harms (e.g., adverse drug effects, costs of therapy) versus benefits of BP lowering in patients at lower risk of cardiovascular disease.1222 1223 1224 1229

Consider potential benefits of hypertension management and drug cost, adverse effects, and risks associated with the use of multiple antihypertensive drugs when deciding a patient's BP treatment goal.1200 1220 1229

For decisions regarding when to initiate drug therapy (BP threshold), the 2017 ACC/AHA hypertension guideline incorporates underlying cardiovascular risk factors.1200 1207 ASCVD risk assessment is recommended by ACC/AHA for all adults with hypertension.1200

ACC/AHA currently recommend initiation of antihypertensive drug therapy in addition to lifestyle/behavioral modifications at an SBP ≥140 mm Hg or DBP ≥90 mm Hg in adults who have no history of cardiovascular disease (i.e., primary prevention) and a low ASCVD risk (10-year risk <10%).1200

For secondary prevention in adults with known cardiovascular disease or for primary prevention in those at higher risk for ASCVD (10-year risk ≥10%), ACC/AHA recommend initiation of antihypertensive drug therapy at an average SBP ≥130 mm Hg or an average DBP ≥80 mm Hg.1200

Adults with hypertension and diabetes mellitus, chronic kidney disease (CKD), or age ≥65 years are assumed to be at high risk for cardiovascular disease; ACC/AHA state that such patients should have antihypertensive drug therapy initiated at a BP ≥130/80 mm Hg.1200 Individualize drug therapy in patients with hypertension and underlying cardiovascular or other risk factors.502 1200

In stage 1 hypertension, experts state that it is reasonable to initiate drug therapy using the stepped-care approach in which one drug is initiated and titrated and other drugs are added sequentially to achieve the target BP.1200 Initiation of antihypertensive therapy with 2 first-line agents from different pharmacologic classes recommended in adults with stage 2 hypertension and average BP >20/10 mm Hg above BP goal.1200

Black hypertensive patients generally tend to respond better to monotherapy with calcium-channel blockers or thiazide diuretics than to β-blockers.229 230 233 265 266 501 504 1200 However, diminished response to β-blockers is largely eliminated when administered concomitantly with a thiazide diuretic.500

Chronic Stable Angina

Long-term management of stable angina pectoris.109 147 1101

β-Blockers are considered first-line anti-ischemic drugs in most patients with chronic stable angina; despite differences in cardioselectivity, intrinsic sympathomimetic activity, and other clinical factors, all β-blockers appear to be equally effective for this use.1101

Non-ST-Segment-Elevation Acute Coronary Syndromes (NSTE ACS)

Used as part of the standard therapeutic measures for managing NSTE ACS, which include unstable angina and non-ST-segment-elevation MI (NSTEMI).1100

Expert guidelines recommend initiation of oral β-blocker therapy within the first 24 hours in patients who do not have manifestations of heart failure, evidence of low-output state, increased risk of cardiogenic shock, or any other contraindications to β-blocker therapy.1100

Continue β-blocker therapy for secondary prevention in patients with stabilized heart failure and reduced systolic function (preferably with bisoprolol, carvedilol, or metoprolol succinate because of proven mortality benefit).1100

Acute MI

Used during acute phase of MI to reduce cardiovascular mortality.527 603 1100

Expert guidelines recommend initiation of oral β-blocker therapy within the first 24 hours in patients who do not have manifestations of heart failure, evidence of low-output state, increased risk of cardiogenic shock, or any other contraindications to β-blocker therapy.527 1100 Because of conflicting evidence of benefit and potential for harm (e.g., cardiogenic shock), experts recommend limiting use of IV β-blockers to patients with refractory hypertension or ongoing ischemia at time of presentation.527

Continue β-blocker therapy for secondary prevention in post-MI patients with left ventricular systolic dysfunction (preferably with bisoprolol, carvedilol, or metoprolol succinate because of proven mortality benefit).525 Although benefits of long-term β-blockade in patients with normal left ventricular function are less well established, experts recommend continuing β-blocker therapy for at least 3 years in such patients.525

Supraventricular Arrhythmias

Has been used in the treatment of supraventricular tachycardia† [off-label] (SVT) (e.g., atrial flutter† [off-label], junctional tachycardia† [off-label], focal atrial tachycardia† [off-label], paroxysmal supraventricular tachycardia† [off-label] [PSVT]).300 301

Vagal maneuvers and/or IV adenosine are considered first-line interventions for acute treatment of SVT when clinically indicated; if such measures are ineffective or not feasible, may consider an IV β-blocker.300 Oral β-blockers may be used for ongoing management.300 Although evidence of efficacy is limited, experts state that overall safety of β-adrenergic blockers warrants use.300

Used to slow ventricular rate in patients with atrial fibrillation or flutter.300 301

Ventricular Arrhythmias

β-Blockers have been used in patients with cardiac arrest precipitated by ventricular fibrillation† or pulseless VT†; however, routine administration after cardiac arrest is potentially harmful and not recommended.400

β-Blockers may be useful in the management of certain forms of polymorphic VT† (e.g., associated with acute ischemia).401

Heart Failure

Management of mild to moderately severe (NYHA class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin (in conjunction with other heart failure therapies [e.g., ACE inhibitors, diuretics, cardiac glycosides]).147 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 215 216 524 800 Used to increase survival and to reduce the risk of hospitalization.524 800

The American College of Cardiology Foundation (ACCF), AHA, and the Heart Failure Society of America (HFSA) recommend therapy with an ACE inhibitor, angiotensin II receptor antagonist, or angiotensin receptor-neprilysin inhibitor (ARNI) in conjunction with a β-blocker, and an aldosterone antagonist in selected patients, to reduce morbidity and mortality in patients with symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) (ACCF/AHA stage C heart failure).800

Initiate a clinical-trial proven β-blocker (bisoprolol, carvedilol, extended-release metoprolol succinate) to reduce the risk of death in patients with chronic heart failure; benefits shown with these β-blockers not considered indicative of a β-blocker class effect.524

Experts recommend that β-blockers be used in conjunction with ACE inhibitors in all patients with asymptomatic heart failure† (i.e., structural heart disease but no signs or symptoms; ACCF/AHA stage B heart failure) with reduced LVEF.524 800

Vascular Headache

Prophylaxis of migraine headache†; not recommended for the treatment of a migraine attack that has already started.231

Metoprolol Dosage and Administration

General

BP Monitoring and Treatment Goals

Administration

Administer orally109 147 or by IV injection.109

Oral Administration

Conventional Tablets

Administer metoprolol tartrate conventional (immediate-release) tablets daily as a single dose or in divided doses, with or immediately following meals.109

Extended-release Tablets

Administer metoprolol succinate extended-release tablets daily as a single dose.147

Extended-release tablets are scored and can be divided.147 However, swallow tablet or half tablet whole; do not chew or crush.147

When switching from conventional tablets to extended-release tablets, administer the same daily dosage.147

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Monitor heart rate, BP, and ECG during IV therapy.603

Discontinue therapy in patients with severe intolerance to IV therapy.109

Rate of Administration

Administer as a rapid IV injection.109

Dosage

Available as metoprolol tartrate and metoprolol succinate; dosage expressed in terms of the tartrate.109 147

Pediatric Patients

Hypertension
Oral

Children 1–17 years of age; immediate-release metoprolol tartrate†: Some experts have recommended initial dosage of 1–2 mg/kg daily given in 2 divided doses.260 Increase dosage as necessary up to a maximum dosage of 6 mg/kg (up to 200 mg) daily given in 2 divided doses.260

Children ≥6 years of age; extended-release metoprolol succinate: Initially, 1 mg/kg (up to 50 mg) daily.602 Adjust dosage according to BP response.602 Safety and efficacy of dosages >2 mg/kg (or >200 mg) once daily not established in pediatric patients.602

Adults

Hypertension
Metoprolol Therapy
Oral

Conventional metoprolol tartrate tablets: Manufacturer states usual initial dosage is 100 mg daily in single or divided doses, either alone or in combination with a diuretic.600 Some experts state usual dosage range is 100–200 mg daily, administered in 2 divided doses.1200

Extended-release metoprolol succinate tablets: Manufacturer states usual initial dosage is 25–100 mg once daily.602 Some experts state usual dosage range is 50–200 mg once daily.1200

Increase dosage at weekly (or longer) intervals until optimum effect is achieved.600 602

If satisfactory BP response is not maintained throughout the day, larger doses, more frequent administration, or use of extended-release tablets may be required.a

Metoprolol/Hydrochlorothiazide Fixed-combination Therapy
Oral

Manufacturer states fixed-combination preparation should not be used for initial antihypertensive therapy; administer each drug separately, then use the fixed combination if the optimum maintenance dosage corresponds to the ratio of drugs in the combination preparation.a

Chronic Stable Angina
Oral

Initially, 100 mg given once daily (extended-release tablets) or in 2 divided doses daily (conventional tablets).109 147 Increase dosage at weekly intervals until optimum response is obtained or pronounced slowing of heart rate occurs.a

Usual maintenance dosage is 100–400 mg daily.147

Acute MI
Early Treatment.
IV, then Oral

Manufacturer recommends 5 mg IV every 2 minutes for 3 doses as tolerated.603 If total IV dose is tolerated, initiate 50 mg orally 15 minutes after the last IV dose and repeat every 6 hours for 48 hours; continue with maintenance dosage of 100 mg twice daily.109 If total IV dose is not tolerated, initiate 25 or 50 mg (depending on the degree of intolerance) orally every 6 hours beginning 15 minutes after the last IV dose or as soon as clinical condition allows.109

ACCF/AHA recommend initiation of oral metoprolol tartrate within the first 24 hours of MI at a dosage of 25–50 mg every 6–12 hours; transition over the following 2–3 days to twice-daily dosing (using metoprolol tartrate) or daily dosing (using metoprolol succinate).527 Titrate up to total daily dose of 200 mg as tolerated.527 Because IV β-blockers can be potentially harmful in patients with risk factors for cardiogenic shock, ACCF/AHA recommend limiting IV use to patients who are hypertensive or have ongoing ischemia at the time of presentation.527 If IV administration is employed, ACCF/AHA recommend dosage of 5 mg every 5 minutes up to 3 doses (as tolerated).527

Late Treatment and Long-term Secondary Prevention
Oral

For late treatment, manufacturer recommends initiation of therapy at 100 mg twice daily as soon as patient's condition allows; continue for at least 3 months.604

Optimal duration of therapy for secondary prevention remains to be clearly established.527 802 804 Experts generally recommend long-term therapy in post-MI patients with left ventricular systolic dysfunction, and at least 3 years of therapy in those with normal left ventricular function.525 802 804 1101

Supraventricular Arrhythmias
Atrial Fibrillation†.
IV, then Oral

2.5–5 mg IV over 2 minutes; may repeat up to 3 doses.301 Then, 25–100 mg orally twice daily (as metoprolol tartrate) or 50–400 mg once daily (as metoprolol succinate) for long-term control.301

SVT (e.g., Atrial Flutter†, PSVT†, Junctional Tachycardia†, Atrial Tachycardia†)
IV, then Oral

Experts recommend initial IV dose of 2.5–5 mg over 2 minutes; may repeat after 10 minutes, up to a total of 3 doses.300

Usual oral maintenance dosage for ongoing treatment is 200 mg twice daily (as metoprolol tartrate) or 400 mg once daily (as metoprolol succinate).300

Heart Failure
Oral

Initially, 25 mg (extended-release tablets) once daily in adults with NYHA class II heart failure.147 In patients with more severe heart failure, use an initial dosage of 12.5 mg (extended-release tablets) once daily.147 Double the dosage every 2 weeks to a dosage of 200 mg or until highest tolerated dosage is reached.147

Some experts recommend initiation of therapy with 12.5–25 mg (extended-release tablets) once daily.524 If tolerated, gradually titrate dosage upward (maximum dosage 200 mg once daily).524

If deterioration occurs during titration, increase dosage of concurrent diuretic147 and decrease dosage of metoprolol or temporarily discontinue metoprolol.147 524 Do not continue dosage titration until symptoms of worsening heart failure have stabilized.147 524 Initial difficulty in dosage titration should not preclude subsequent attempts to successfully titrate the dosage.147

Reduce dosage in patients with heart failure who experience symptomatic bradycardia (e.g., dizziness) or 2nd or 3rd degree heart block.147 524

Vascular Headache
Migraine†
Oral

Dosages of 50–300 mg daily have been used in clinical studies; usual effective dosage was 200 mg daily.231

Prescribing Limits

Pediatric Patients

Hypertension
Oral

Immediate-release metoprolol tartrate†: Maximum 6 mg/kg (up to 200 mg) daily.260

Extended-release metoprolol succinate: Safety and efficacy of dosages >2 mg/kg (or >200 mg) once daily not established.602

Adults

Hypertension
Oral

Dosages >400 mg (extended-release tablets) and 450 mg (conventional tablets) daily have not been studied.600 602

Chronic Stable Angina
Oral

Dosages >400 mg daily have not been studied.109 147

Acute MI
IV

Maximum 15 mg over 6–15 minutes.527 603

Heart Failure
Oral

Up to 200 mg daily.147

Special Populations

Hepatic Impairment

Elimination occurs mainly in the liver; dosage reductions may be necessary.109 a

Renal Impairment

Dosage adjustments are not required.109 147

Geriatric Patients

Cautious dosage selection recommended; initiate therapy at the lower end of the dosage range.147

Detailed Metoprolol dosage information

Cautions for Metoprolol

Contraindications

Warnings/Precautions

Warnings

Abrupt Withdrawal of Therapy

Abrupt discontinuance may exacerbate angina symptoms or precipitate MI in patients with CAD.109 147 a Avoid abrupt discontinuance.109 147 Gradually decrease dosage over 1–2 weeks and monitor patients carefully.109 147 If exacerbation of angina occurs or acute coronary insufficiency develops, reinstitute therapy promptly, at least temporarily, and initiate appropriate measures for the management of unstable angina.109 147

Heart Failure

Possible precipitation of heart failure;109 possible decreased exercise tolerance in patients with left ventricular dysfunction.a

Initiate therapy and subsequent dosage adjustments in patients with heart failure under close medical supervision.147 524 Prior to initiation of metoprolol, stabilize patient on other heart failure therapy (e.g., ACE inhibitor, diuretic, cardiac glycoside).147 Symptomatic improvement may not be evident for 2–3 months after initiating therapy.163 205

Avoid use in patients with decompensated heart failure;147 a use cautiously in patients with inadequate myocardial function and, if necessary, in patients with well-compensated heart failure (e.g., those controlled with ACE inhibitors, cardiac glycosides, and/or diuretics);147 a use with extreme caution in patients with substantial cardiomegaly.a

Adequate treatment (e.g., with a cardiac glycoside and/or diuretic) and close observation recommended if signs or symptoms of impending heart failure occur; if heart failure continues, discontinue therapy, gradually if possible.109 147

Bronchospastic Disease

Possible bronchoconstriction, especially at dosages >100 mg daily.109 a

Use with caution in patients with bronchospastic disease; administer lowest effective dosage (initially in 3 divided doses) and with maximal therapy with a β2-adrenergic agonist.109 a

Bradycardia

Possible bradycardia and depressed SA node automaticity.109 147 a

Carefully monitor hemodynamic status of patients with MI; use with caution in patients with sinus node dysfunction.109 147 a

If heart rate < 40 bpm with evidence of decreased cardiac output, administer IV atropine; if bradycardia is refractory to atropine, discontinue metoprolol and consider cautious administration of isoproterenol or use of a cardiac pacemaker.109

AV Block

Possible intensification of AV block, AV dissociation, AV conduction delays,281 complete heart block, or cardiac arrest, especially in patients with preexisting heart block caused by digoxin or other factors.109 a

Use with caution, if at all, in patients with AV conduction defects.a

If heart block occurs in patients with MI, discontinue metoprolol and administer IV atropine; if the heart block is refractory to atropine, consider cautious administration of isoproterenol or use of a cardiac pacemaker.109

Hypotension

If hypotension (systolic BP <90 mm Hg) occurs in patients with MI, discontinue metoprolol and assess hemodynamic status and extent of myocardial damage.109 Invasive monitoring of central venous, pulmonary capillary wedge, and arterial pressures may be necessary; appropriate therapy with IV fluids and other treatment modalities recommended.109

If hypotension is associated with severe bradycardia or heart block, provide treatment directed at reversing these.109 (See Bradycardia and also see AV Block under Cautions.)

Major Surgery

Possible increased risks associated with general anesthesia (e.g., severe hypotension, maintenance of heart beat) due to decreased ability of the heart to respond to reflex β-adrenergic stimuli.109 147

Use with caution in patients undergoing major surgery involving general anesthesia; avoid use of anesthetics that cause myocardial depression (see Specific Drugs under Interactions).a

Diabetes and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia, palpitation, BP changes, tremor, feelings of anxiety) and increased insulin-induced hypoglycemia.109 147 a

Use with caution in patients with diabetes mellitus.109 147

Thyrotoxicosis

Signs of hyperthyroidism (e.g., tachycardia) may be masked.109 147 Possible thyroid storm if therapy is abruptly withdrawn; carefully monitor patients having or suspected of developing thyrotoxicosis.109 147

General Precautions

Ocular Effects

Possible dry eyes and decreased tear production, minimal injection of conjunctivae and/or eyelids, punctate keratitis, keratoconjunctivitis or corneal ulceration.a Close observation recommended.a

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription; similarity in spelling between Toprol-XL (metoprolol succinate) and Topamax (trade name for topiramate, an anticonvulsant and antimigraine agent) may result in errors.261 262 263 264

Potential also exists for dispensing errors involving confusion between Toprol-XL and Tegretol or Tegretol-XR (trade names for carbamazepine, an anticonvulsant also used for relief of pain associated with trigeminal neuralgia, as well as for various psychiatric disorders).261 263

These medication errors have been associated with serious adverse events sometimes requiring hospitalization as a result of either lack of the intended medication (e.g., seizure recurrence, return of hallucinations, suicide attempt, hypertension recurrence) or exposure to the wrong drug (e.g., bradycardia in a patient erroneously receiving metoprolol).261 262 263 264 261 262 263 264

Use of Fixed Combinations

When used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.a

Specific Populations

Pregnancy

Category C.109 147

Lactation

Distributed into milk.147 Use with caution.109

Pediatric Use

Safety and efficacy of metoprolol tartrate remain to be fully established in children;109 147 however, some experts have recommended dosages for hypertension based on current limited clinical experience.

Safety and efficacy of metoprolol succinate have been evaluated in hypertensive children ≥6 years of age (see Pediatric Patients under Dosage and Administration); however, safety and efficacy not established in children <6 years of age.602

Geriatric Use

Among patients with heart failure, safety and efficacy profiles in geriatric individuals are similar to those in younger adults.147

Hepatic Impairment

Hepatic elimination; use with caution.109 147 a

Common Adverse Effects

Dizziness, tiredness, insomnia, gastric upset.a

Drug Interactions

Metabolized by CYP2D6.147 200 201 202 208 210 211

Drugs Affecting Hepatic Microsomal Enzymes

CYP2D6 inhibitors: Potential pharmacodynamic (increased β-adrenergic blockade, decreased cardioselectivity of metoprolol) and pharmacokinetic interaction (prolonged half-life and increased plasma concentrations of metoprolol).147 200 201 202 208 210 211

Specific Drugs

Drug

Interaction

Comments

Calcium-channel blocking agents, nondihydropyridine

Possible additive negative effects on SA or AV nodal conductiona

Digoxin

Possible additive negative effects on SA or AV nodal conductiona

Diuretics

Increased hypotensive effecta

Adjust dosage carefullya

Fluoxetine

Possible increased plasma metoprolol concentrations; potential for increased β-adrenergic blockade and decreased cardioselectivity of metoprolol147 200 201 202 208 210 211

Anesthetics, general (myocardial depressant agents [e.g., diethyl ether])

Increased risk of hypotension and heart failure109

Avoid use of general anesthetics with myocardial depressant effectsa

Hydralazine

Increased risk of pulmonary hypertension in patients with uremia a

Hypotensive agents

Possible increased hypotensive effecta

Adjust dosage carefullya

Paroxetine

Possible increased plasma metoprolol concentrations; potential for increased β-adrenergic blockade and decreased cardioselectivity of metoprolol147 200 201 202 208 210 211

Use with caution209 211 212

Propafenone

Possible increased plasma metoprolol concentrations; potential for increased β-adrenergic blockade and decreased cardioselectivity of metoprolol147 200 201 202 208 210 211

Quinidine

Possible increased plasma metoprolol concentrations; potential for increased β-adrenergic blockade and decreased cardioselectivity of metoprolol147 200 201 202 208 210 211

Reserpine

Additive effects109

Monitor for hypotension and bradycardia109

Sertraline

Possible increased plasma metoprolol concentrations; potential for increased β-adrenergic blockade and decreased cardioselectivity of metoprolol147 200 201 202 208 210 211

When concomitant sertraline therapy is discontinued, may need to increase metoprolol dosage208

Sympathomimetic agents

Antagonism of β1-adrenergic stimulating effectsa

Verapamil

Increased oral bioavailability105 106

Avoid concomitant use, if possible;105 106 if used concomitantly, adjust metoprolol dosage and monitor patient closely106
Metoprolol drug interactions (more detail)

Metoprolol Pharmacokinetics

Absorption

Bioavailability

Metoprolol tartrate is rapidly and almost completely absorbed from the GI tract.109 After an oral dose (as conventional tablets), about 50% of the drug undergoes first-pass metabolism in the liver.109

Peak plasma concentrations are reached in about 90 minutes following a single oral dose as conventional tabletsa or 7 hours following administration as extended-release tablets.148

Steady-state oral bioavailability of extended-release tablets given once daily is about 77% of that of conventional tablets at corresponding dosages.147 148 Following oral administration as extended-release tablets, peak plasma metoprolol concentrations are about 25–50% of those attained after administration of conventional tablets.147

Plasma concentrations attained after IV administration are approximately twice those attained following oral administration.a

Onset

Reduction in systolic BP during exercise reported within 15 minutes after a single oral dose of metoprolol tartrate 50–80 mg; with chronic therapy, effect on systolic BP usually is maximal within 1 week.a

The extended-release tablets, given once daily, produce similar hypotensive effects as conventional tablets at similar dosages.147 148

Maximum β-adrenergic blocking activity occurs at 20 minutes after a 10-minute IV infusion.109

Duration

Reduction in systolic BP during exercise persisted for 6 hours following a single oral dose of metoprolol tartrate 50–80 mg.a Hypotensive effect of extended-release tablets may persist for 24 hours.147 Duration of β-adrenergic blocking effect is dose related.109

Following IV infusion of metoprolol tartrate 5 or 15 mg, β-adrenergic blocking activity persisted for approximately 5 or 8 hours, respectively.109

Food

Food does not affect bioavailability of extended-release tablets.147

When conventional tablets are administered with food, peak plasma concentrations are higher and the extent of absorption is increased.a

Distribution

Extent

Widely distributed into body tissues.a Concentrations in heart, liver, lungs, and saliva exceed plasma concentration.a Crosses the blood-brain barrier;147 concentration in CSF is about 78% of the simultaneous plasma concentration.a

Crosses the placenta.a

Concentration in milk is about 3–4 times the maternal plasma concentrations, but the actual amount distributed into milk appears to be very small.101 102

Plasma Protein Binding

11–12% (albumin).109

Elimination

Metabolism

Undergoes first-pass metabolism in the liver by CYP2D6 to inactive metabolites.109 147

Elimination Route

Excreted in urine, principally as metabolites.109

Half-life

3–4 hours.109

Special Populations

Half-life does not increase appreciably with impaired renal function.109

Half-life is about 7.6 hours in poor metabolizers of the drug.a Concomitant use of CYP2D6 inhibitors (see Drugs Affecting Hepatic Microsomal Enzymes under Interactions) in poor metabolizers will lead to increases in plasma metoprolol concentrations and a decrease in β1-selectivity.147

Stability

Storage

Oral

Tablets

Tight, light-resistant containers at 15–30°C.109 Protect from light.109

Extended-Release Tablets

25°C (may be exposed to 15–30°C).147

Parenteral

Injection

30°C or less (preferably 15–30°C).109 Protect from light109 and freezing.a

Compatibility

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in water

Sodium chloride 0.9%
Drug Compatibility
Y-Site CompatibilityHID

Compatible

Abciximab

Alteplase

Amiodarone HCl

Argatroban

Bivalirudin

Ceftaroline fosamil

Diltiazem HCl

Eptifibatide

Furosemide

Heparin sodium

Meperidine HCl

Milrinone lactate

Morphine sulfate

Procainamide HCl

Sodium nitroprusside

Incompatible

Amphotericin B cholesteryl sulfate complex

Lidocaine HCl

Nitroglycerin

Variable

Nesiritide

Actions

Advice to Patients

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Metoprolol Succinate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, extended-release, film-coated

23.75 mg (equivalent to 25 mg of metoprolol tartrate)*

Metoprolol Succinate Extended-release Tablets

Toprol XL (scored)

AstraZeneca

47.5 mg (equivalent to 50 mg of metoprolol tartrate)*

Metoprolol Succinate Extended-release Tablets

Toprol XL (scored)

AstraZeneca

95 mg (equivalent to 100 mg of metoprolol tartrate)*

Metoprolol Succinate Extended-release Tablets

Toprol XL (scored)

AstraZeneca

190 mg (equivalent to 200 mg of metoprolol tartrate)*

Metoprolol Succinate Extended-release Tablets

Toprol XL (scored)

AstraZeneca

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Metoprolol Tartrate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

50 mg*

Lopressor (scored)

Validus

Metoprolol Tartrate Tablets

100 mg*

Lopressor (scored)

Validus

Metoprolol Tartrate Tablets

Parenteral

Injection

1 mg/mL

Lopressor

Novartis

Metoprolol Tartrate Injection

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Metoprolol Tartrate and Hydrochlorothiazide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

50 mg Metoprolol Tartrate and Hydrochlorothiazide 25 mg*

Lopressor HCT (scored)

Validus

Metoprolol Tartrate and Hydrochlorothiazide Tablets

100 mg Metoprolol Tartrate and Hydrochlorothiazide 25 mg*

Lopressor HCT (scored)

Validus

Metoprolol Tartrate and Hydrochlorothiazide Tablets

100 mg Metoprolol Tartrate and Hydrochlorothiazide 50 mg*

Lopressor HCT (scored)

Validus

Metoprolol Tartrate and Hydrochlorothiazide Tablets

AHFS DI Essentials™. © Copyright 2024, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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