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Esmolol (Monograph)

Brand name: Brevibloc
Drug class: beta-Adrenergic Blocking Agents
VA class: CV100
Chemical name: 4-[2-Hydroxy-3-[(1-methylethyl)amino]propoxy]benzenepropanoic acid methyl ester hydrochloride
Molecular formula: C16H25NO4•ClH
CAS number: 81161-17-3

Medically reviewed by Drugs.com on Feb 22, 2024. Written by ASHP.

Warning

A standardized concentration for this drug has been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. The drug is included in a standard concentration list which may apply to an IV or oral compounded liquid formulation. For additional information, see the ASHP website [Web].

Introduction

Short-acting β1-selective adrenergic blocking agent.1 2 17 18 113

Uses for Esmolol

Supraventricular Arrhythmias

Rapid, temporary control of ventricular rate in patients with supraventricular tachycardia (SVT) (e.g., atrial flutter and/or fibrillation, sinus tachycardia, junctional tachycardia, atrial tachycardia).1 2 53 54 55 56 57 58 59 68 87 88 100 113 300 301

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-adrenergic blocking agent.300 Although evidence of efficacy is limited, experts state that overall safety of β-blockers warrants use.300

May be used in patients with nonpreexcited atrial flutter and/or fibrillation to control rapid heart rate associated with surgical or other manipulative procedures (e.g., cardiac catheterization), or other emergent situations requiring short-term control of ventricular rate.1 2 5 51 52 53 54 55 56 57 58 59 68 87 88 100 113 300 301

May be useful in patients with noncompensatory sinus tachycardia for short-term control of rapid heart rate requiring intervention.1 2 37 59 60 61 62 63 64 65 66 67 68

Not intended for chronic use when other more appropriate antiarrhythmic agents would be preferred.1 2

Hypertension

Treatment of intraoperative and postoperative hypertension and/or tachycardia.74 109 113 542 a Has been used effectively for prevention or treatment of increases in BP associated with surgical events.63 64 71 72 73 74 75 109 113 125 However, use for prevention of such events is not recommended by the manufacturer.a

Management of hypertensive emergencies in adults.542 1200

Rapid reduction of BP in the management of acute severe hypertension in pediatric patients† [off-label] with life-threatening symptoms.1150

Treatment to produce controlled hypotension† [off-label] during anesthesia in order to reduce bleeding resulting from surgical procedures (e.g., orthopedic surgery, neurosurgery).75 114 124

Acute Myocardial Ischemia

Has been used for the management of acute tachyarrhythmias complicating acute MI† [off-label]15 24 25 and to minimize myocardial ischemia following acute MI† [off-label]13 15 24 25 58 113 or associated with unstable angina† [off-label].15 24 58 82 113

While current expert guidelines recommend an oral β-blocker in all patients with MI 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, use of IV β-blockers should be limited to patients with refractory hypertension or ongoing ischemia. 527 1100

Esmolol Dosage and Administration

General

Hypertensive Emergency and Acute Severe Hypertension

Administration

Administer by IV infusion.1

May administer by direct IV injection for immediate control of intraoperative tachyarrhythmia and/or hypertension.a

Continuous infusion is preferred for rapid BP reduction in children† due to short duration of action.1150

IV Administration

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

IV infusion usually administered via controlled infusion device to facilitate dosage titration.52 53 54 61 114 126

Take care to avoid extravasation.600 Avoid using butterfly needles and very small veins for infusion.1 114 Use alternate infusion site if local reaction occurs at infusion site.1 Severe infusion site reactions have occurred, particularly after extravasation (see Extravasation under Cautions).600

Do not introduce additives into premixed solutions in ready-to-use bags.1 a

Do not use the premixed injection in series connections with other plastic containers since such use could result in air embolism.1

Infusion bag for premixed solution contains 2 outlet ports.1 Use medication port on the bag only for withdrawing an initial loading dose for direct IV injection.a Sterility cannot be guaranteed with repeated withdrawals; once drug has been withdrawn from the bag, use the solution within 24 hours.a

Esmolol hydrochloride injection (10 mg/mL) in ready-to-use vials may be used to administer loading doses.600

Rate of Administration

Administer 500-mcg/kg loading doses over 1 minute, followed by IV infusion of the drug.a Rate of IV infusion determined by patient response and tolerance.1 51 52 53 54 55 58 59 60 61 64 65 66 67 68

For immediate control of intraoperative or postoperative hypertension and/or tachycardia, administer initial 1-mg/kg loading dose by IV injection over 30 seconds, followed by IV infusion, if necessary.600

Dosage

Available as esmolol hydrochloride; dosage expressed in terms of the salt.a

Pediatric Patients

Acute Severe Hypertension
Rapid Reduction of BP†
IV

Children and adolescents: 100–500 mcg/kg per minute as continuous infusion.1150

Adults

SVT
IV

Loading dose of 500 mcg/kg per minute for 1 minute,1 51 52 53 54 55 58 300 301 followed by maintenance infusion of 50 mcg/kg per minute for 4 minutes.1 2 3 51 52 53 54

If desired response is not attained within first 5 minutes, may increase infusion rate in 50-mcg/kg per minute increments (i.e., to 100 mcg/kg per minute, then to 150 mcg/kg per minute) up to a maximum of 200 mcg/kg per minute; maintain each new rate for 4 or more minutes.1

Adjust rate and duration of infusion carefully according to patient’s tolerance and response (as indicated by ventricular rate and BP).1 51 52 53 54 55 58

Average maintenance dosage: 100 mcg/kg per minute (range: 50–200 mcg/kg per minute).1 2 3 51 52 53 54 55 58 Maintenance dosages up to 300 mcg/kg per minute have been used occasionally.1 2 3 51 52 53 54 55 58 300 301 Adequate rate control may occur with dosage as low as 25 mcg/kg per minute.1 55

Transfer to alternative antiarrhythmic therapy (e.g., longer-acting β-blocker, digoxin, verapamil) when adequate control of heart rate has been achieved and patient is stabilized.1

Rapid Dosage Titration (if rapid slowing of ventricular response is required)
IV

Loading dose of 500 mcg/kg per minute for 1 minute,1 51 52 53 54 55 58 followed by maintenance infusion of 50 mcg/kg per minute for 4 minutes.1 2 3 51 52 53 54

Administer second loading dose of 500 mcg/kg per minute for 1 minute,1 2 3 51 52 53 54 followed by maintenance infusion of 100 mcg/kg per minute for 4 minutes.1 2 3 51 52 53 54

If necessary, administer a third and final loading dose of 500 mcg/kg per minute for 1 minute, followed by 150 mcg/kg per minute for 4 minutes.1 52 55 57 58

If needed (without a fourth loading dose), increase maintenance dosage to maximum of 200 mcg/kg per minute.1 52 55 57 58

Once the desired ventricular rate1 or a patient tolerance end point (e.g., reduction in BP)52 53 54 has been nearly achieved,1 114 omit loading doses and titrate maintenance infusion rate upward (to 200 mcg/kg per minute) or downward as appropriate; may increase interval between dosage increments.1

Transfer to Alternative Antiarrhythmics
IV

Decrease esmolol infusion rate by 50% 30 minutes after the first dose of the alternative drug; if adequate response is maintained for ≥1 hour after the second dose of the alternative drug, discontinue esmolol.1

Consider dosing guidelines for the alternative drug when determining the appropriateness of this guideline for transferring therapy.1

Hypertension
Immediate Control of Intraoperative and Postoperative Hypertension and/or Tachycardia
IV

1 mg/kg by direct IV injection over 30 seconds; if necessary, follow with IV infusion of 150 mcg/kg per minute.600

Adjust as required to maintain desired heart rate (maximum 200 mcg/kg per minute) and/or BP (maximum 300 mcg/kg per minute).600

Gradual Control of Intraoperative and Postoperative Hypertension and/or Tachycardia
IV

Loading dose of 500 mcg/kg per minute for 1 minute followed by maintenance infusion of 50 mcg/kg per minute for 4 minutes.a If desired response is not attained within first 5 minutes, administer second loading dose of 500 mcg/kg per minute for 1 minute followed by maintenance infusion of 100 mcg/kg per minute.a

Adjust dosage using titration schedule recommended for treatment of SVT;1 however, higher dosages (e.g., 250–300 mcg/kg per minute) may be required for adequate control of BP.1

Hypertensive Emergency
IV

Loading dose of 500–1000 mcg/kg over 1 minute, followed by 50 mcg/kg per minute by IV infusion; may repeat loading dose and increase infusion rate in increments of 50 mcg/kg per minute as needed to a maximum of 200 mcg/kg per minute.1200

Production of Controlled Hypotension† during Anesthesia
IV

Dosage has been titrated upward to a level necessary to maintain the required reduction in BP (e.g., a 15% reduction in mean arterial pressure) or until maximum rate of 300 mcg/kg per minute is reached.75 124 126

Prescribing Limits

Adults

SVT
IV

Manufacturer recommends maximum maintenance dosage of 200 mcg/kg per minute.a Maintenance dosages as high as 300 mcg/kg per minute have been used1 2 3 51 52 53 54 55 58 but provide little added benefit and increase the incidence of adverse effects.1 2 51 53 58 114 Safety of maintenance dosages >300 mcg/kg per minute not established.1 3

Administered for ≤24 hours in most patients;1 2 55 limited data indicate that infusions may be well tolerated for up to 48 hours.1

Hypertension
Intraoperative and Postoperative Hypertension and/or Tachycardia
IV

Tachycardia: Maximum 200 mcg/kg per minute.600 Higher dosages provide little additional benefit in lowering heart rate but increase risk of adverse effects.600

Hypertension: Safety of dosages >300 mcg/kg per minute not established.600

Hypertensive Emergency
IV

Maximum 200 mcg/kg per minute.1200

Special Populations

Renal Impairment

Administer with caution, especially in patients with severe renal impairment.1 2

Detailed Esmolol dosage information

Cautions for Esmolol

Contraindications

Warnings/Precautions

Warnings

Hypotension

Risk of hypotension,1 2 24 50 51 54 55 56 57 58 59 63 100 113 114 122 occasionally symptomatic (e.g., manifested as diaphoresis or dizziness).1 2 50 51 54 55 58 Can occur at any dose level but usually is dose related.1 2 51 53 58 Doses >200 mcg/kg per minute not recommended by manufacturer for SVT management.1 2 114

Dosage reduction or discontinuance of drug usually results in reversal of hypotension within 30 minutes.1

Monitor BP closely, especially in patients with low pretreatment BP (e.g., SBP <105 mm Hg).1 2 55 58 114

Intraoperative or Postoperative Hypertension

Do not use when hypertension is principally due to hypothermia-associated vasoconstriction.1

Cardiac Failure

Possible precipitation of heart failure in patients with inadequate cardiac function; use with caution in such patients.1 2 Prolonged β-adrenergic blockade may lead to cardiac failure in patients with latent cardiac insufficiency.104

Avoid use in patients with overt heart failure.1 Use cautiously, if necessary, in patients with compensated heart failure (e.g., those controlled with cardiac glycosides and/or diuretics).1

Discontinue at first sign or symptom of impending cardiac failure;1 if necessary, initiate specific therapy (e.g., a cardiac glycoside and/or diuretic).1 2 If continued esmolol therapy is necessary, may restart esmolol infusion at a slower rate once manifestations of cardiac failure have subsided.114

Bronchospastic Disease

In general, do not use β-blockers in patients with bronchospastic disease;1 2 105 106 107 116 117 however, may use esmolol with caution due to its relative β1-selective adrenergic blocking activity and short duration of action.1 2 Administer lowest effective dose since β1-selectivity is not absolute.1 2

Discontinue immediately if bronchospasm occurs.1 May administer a β2-adrenergic agonist (bronchodilator), but use extreme caution since the patient may have a preexisting rapid ventricular rate.1 2

Diabetes and Hypoglycemia

Possible decreased signs and symptoms of hypoglycemia (e.g., tachycardia, palpitation, BP changes, tremor, feelings of anxiety, but not sweating or dizziness) and increased insulin-induced hypoglycemia.1 2 108

Use with caution in patients with diabetes mellitus or hypoglycemia.1 2

General Precautions

Adverse effects generally resolve more rapidly than with other β-blockers because of esmolol’s short duration of action.1 2 3 4 5 113

Cardiovascular Precautions

Use with caution in patients with SVT who are compromised hemodynamically or are taking drugs that reduce peripheral resistance, myocardial filling, myocardial contractility, and/or electrical impulse propagation in the myocardium.1

Use IV β-blockers, including esmolol, with caution in patients with acute atrial fibrillation who have overt congestion, hypotension, or heart failure with reduced ejection fraction.301

Deaths have been reported in patients with complex clinical states receiving esmolol (presumably to control ventricular rate).1

History of Anaphylactic Reactions

Patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated, accidental, diagnostic, or therapeutic challenge with such allergens and less responsive to usual doses of epinephrine.1

Abrupt Withdrawal of Therapy

Abrupt discontinuance has not produced the withdrawal effects (e.g., exacerbation of angina symptoms, precipitation of MI) associated with abrupt discontinuance of other β-adrenergic blocking agents used chronically.1 However, consider the possibility that such effects could occur with esmolol in patients with coronary artery disease; use caution when esmolol infusions are stopped abruptly in such patients.1

Extravasation

Avoid extravasation.1 Infusion site reactions, including irritation, inflammation, and severe reactions (e.g., thrombophlebitis, necrosis, blistering), have occurred, particularly following extravasation.600 (See IV Administration under Dosage and Administration.)

Specific Populations

Pregnancy

Category C.a

Lactation

Not known whether esmolol is distributed into milk.1 Use with caution in nursing women.1

Pediatric Use

Safety and efficacy not established in children <18 years of age.1 114

May cause profound bradycardia when used for rapid reduction of BP in pediatric patients with acute severe hypertension†.1150

Renal Impairment

Use with caution in patients with renal impairment, especially severe impairment; de-esterified metabolite (ASL 8123) is eliminated mainly by the kidneys.1 2 47

Common Adverse Effects

Hypotension,1 2 24 50 51 53 54 55 56 57 58 59 63 100 113 114 122 dizziness,1 2 51 54 55 58 113 122 diaphoresis,1 2 50 51 54 55 58 113 122 headache,1 2 51 55 58 59 113 somnolence,1 2 50 55 58 113 confusion,1 2 55 58 113 agitation,1 2 55 58 63 113 nausea,1 2 51 55 56 58 59 113 infusion site reactions1 2 (e.g., inflammation,1 2 54 55 58 induration).1 2 55 58 59

Drug Interactions

Specific Drugs

Drug

Interaction

Comments

Digoxin

Possible increase in serum digoxin concentrations;1 2 49 113 esmolol pharmacokinetics unaffected1 2 49 113

Used safely and effectively; combined therapy apparently somewhat more effective than esmolol alone in lowering heart rate59 113

Verapamil

Rare but serious adverse reactions (including fatal cardiac arrest) with concomitant IV β-blocker and IV verapamil, especially in patients with severe cardiomyopathy, heart failure, or recent MI1 141

Mibefradil (no longer commercially available in US)

Slowing or complete suppression of SA node activity, with slow ventricular rates139 140

Vasoconstrictors or inotropes (e.g., dopamine, epinephrine, norepinephrine)

Potential for blocked cardiac contractility when systemic vascular resistance is high1

Do not use esmolol to control SVT in patients receiving vasoconstrictive or inotropic drugs1

Catecholamine-depleting drugs (e.g., reserpine)

Possible additive effects1

Monitor closely for marked bradycardia or hypotension1

Morphine

Increased esmolol concentrations; morphine pharmacokinetics not affected1 2 49 113

Titrate esmolol dosage carefully1 2 49

Neuromuscular blocking agents (succinylcholine)

Possible prolonged duration of neuromuscular blockade1 2 113

Apparently not clinically important1 2 86 114

Warfarin

Slight increase in esmolol concentrations;1 2 49 113 warfarin concentrations not affected1 2 49 113

Titrate esmolol dosage carefully1
Esmolol drug interactions (more detail)

Esmolol Pharmacokinetics

Absorption

Onset

Following rapid IV injection, 13–18% decrease in heart rate within 1 minute, 11–18% decrease in SBP within 2 minutes, and 13–22% prolongation of PR interval within 4 minutes after IV injection.41

In patients with SVT, 15–20% reduction in heart rate apparent within 5–22 minutes after initiation of IV infusion.59 68

Duration

Following discontinuance of IV infusion, β-blockade dissipates within about 1–2 minutes, substantial recovery occurs within about 10–20 minutes, and complete reversal occurs within about 20–30 minutes.1 2 5 27 34 39 113

Distribution

Extent

Distributed into liver and kidneys, but only minimally into CSF, spleen, or testes of rats.2 28 Rapidly and widely distributed in humans.2 39 99 113

Not known whether esmolol and/or ASL 8123 crosses the placenta in humans, 126 but the drug crosses the placenta in animals.114 115

Not known whether esmolol and/or ASL 8123 are distributed into milk.1

Plasma Protein Binding

Esmolol: 55%1 2 28 113 (albumin and α1-acid glycoprotein).28

Metabolite (ASL 8123): Approximately 10%.1 2 113

Elimination

Metabolism

Hydrolyzed rapidly, principally by esterases (probably arylesterase) in erythrocytic cytosol,1 2 39 40 45 46 99 113 to de-esterified (acid) metabolite (ASL 8123) and methanol.1 2 39 40 45 46 113 Acid metabolite has no appreciable β-blocking activity in humans.1 2 40

Elimination Route

Excreted principally in urine as the acid metabolite (73–88%); less than 2% excreted unchanged in urine.1 2 5 39 47 113 Small amounts (<5%) may be eliminated in feces.28 114

Half-life

Biphasic;1 2 39 99 113 distribution half-life of esmolol is about 2 minutes; 1 2 39 99 terminal elimination half-life is about 9 minutes (range: 5–23 minutes).1 2 39 40 99 114

Special Populations

In patients with renal impairment, elimination half-life of the metabolite may be increased up to 10-fold, but accumulation is not clinically important since ASL 8123 has only minimal β-blocking activity.2 43

About 24% (as metabolite) is removed by hemodialysis,114 and 21% by peritoneal dialysis;114 amount removed depends on several factors (e.g., dialysis flow-rate, dwell time).131 132 133 134

Stability

Storage

Parenteral

Injection

25°C (may be exposed to 15–30°C).1 a Do not freeze; protect from excessive heat.1 a

Compatibility

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in Ringer’s injection

Dextrose 5% in Ringer’s injection, lactated

Dextrose 5% in sodium chloride 0.45 or 0.9%

Dextrose 5% in water

Dextrose 5% in water with potassium chloride 40 mEq/L

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%
Drug Compatibility

Manufacturer states that additives should not be introduced into premixed solutions in ready-to-use bags.a

Admixture CompatibilityHID

Compatible

Aminophylline

Atracurium besylate

Heparin sodium

Incompatible

Diazepam2

Furosemide2 119

Procainamide HCl

Variable

Sodium bicarbonate1 2 3 HID
Y-Site CompatibilityHID

Compatible

Amikacin sulfate

Aminophylline

Amiodarone HCl

Ampicillin sodium

Atracurium besylate

Bivalirudin

Butorphanol tartrate

Calcium chloride

Cefazolin sodium

Ceftazidime

Chloramphenicol sodium succinate

Clindamycin phosphate

Co-trimoxazole

Dexmedetomidine HCl

Diltiazem HCl

Dopamine HCl

Doripenem

Enalaprilat

Erythromycin lactobionate

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Gentamicin sulfate

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%

Insulin, regular

Labetalol HCl

Linezolid

Magnesium sulfate

Methyldopate HCl

Metronidazole

Micafungin sodium

Midazolam HCl

Morphine sulfate

Nafcillin sodium

Nicardipine HCl

Nitroglycerin

Norepinephrine bitartrate

Pancuronium bromide

Penicillin G potassium

Phenytoin sodium

Polymyxin B sulfate

Potassium chloride

Potassium phosphates

Propofol

Ranitidine HCl

Remifentanil HCl

Sodium acetate

Sodium nitroprusside

Streptomycin sulfate

Tacrolimus

Tobramycin sulfate

Vancomycin HCl

Vecuronium bromide

Incompatible

Amphotericin B cholesteryl sulfate complex

Furosemide

Pantoprazole sodium

Warfarin sodium

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

Esmolol Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV use

10 mg/mL (100 mg)*

Brevibloc

Baxter

Esmolol Hydrochloride Injection
Esmolol Hydrochloride in Sodium Chloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV use

10 mg/mL (2.5 g) in 0.59% Sodium Chloride Injection

Brevibloc Premixed

Baxter

20 mg/mL (2 g) in 0.41% Sodium Chloride Injection

Brevibloc Double Strength Premixed

Baxter

AHFS DI Essentials™. © Copyright 2024, Selected Revisions March 3, 2022. 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.

References

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