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.

Introduction

Short-acting β₁-selective adrenergic blocking agent.

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).

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

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.

May be useful in patients with noncompensatory sinus tachycardia for short-term control of rapid heart rate requiring intervention.

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

Hypertension

Treatment of intraoperative and postoperative hypertension and/or tachycardia. Has been used effectively for prevention or treatment of increases in BP associated with surgical events. However, use for prevention of such events is not recommended by the manufacturer.

Management of hypertensive emergencies in adults.

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

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

Acute Myocardial Ischemia

Has been used for the management of acute tachyarrhythmias complicating acute MI^{† [off-label]} and to minimize myocardial ischemia following acute MI^{† [off-label]} or associated with unstable angina^{† [off-label]}.

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.

Related/similar drugs

amlodipine, lisinopril, metoprolol, losartan, furosemide, hydrochlorothiazide, diltiazem

Esmolol Dosage and Administration

General

Hypertensive Emergency and Acute Severe Hypertension

• Initial goal of IV therapy in adults without a compelling indication is to reduce SBP by ≤25% within the first hour, followed by further BP reduction if stable to 160/110 or 160/100 mm Hg within the next 2–6 hours; avoid excessive declines in BP that could precipitate renal, cerebral, or coronary ischemia. If this BP is well tolerated and the patient is clinically stable, may implement further gradual reductions toward normal BP in the next 24–48 hours.

• Adults with severe preeclampsia or eclampsia or pheochromocytoma crisis: Reduce SBP to <140 mm Hg during the first hour.

• Adults with aortic dissection: Reduce SBP to <120 mm Hg within the first 20 minutes.

• Pediatric patients: Reduce BP by ≤25% of the planned reduction over the first 8 hours.

Administration

Administer by IV infusion.

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

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

IV Administration

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

IV infusion usually administered via controlled infusion device to facilitate dosage titration.

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

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

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

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

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

Rate of Administration

Administer 500-mcg/kg loading doses over 1 minute, followed by IV infusion of the drug. Rate of IV infusion determined by patient response and tolerance.

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.

Dosage

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

Pediatric Patients

Acute Severe Hypertension

Rapid Reduction of BP†

IV

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

Adults

SVT

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.

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.

Adjust rate and duration of infusion carefully according to patient’s tolerance and response (as indicated by ventricular rate and BP).

Average maintenance dosage: 100 mcg/kg per minute (range: 50–200 mcg/kg per minute). Maintenance dosages up to 300 mcg/kg per minute have been used occasionally. Adequate rate control may occur with dosage as low as 25 mcg/kg per minute.

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.

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

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.

Administer second loading dose of 500 mcg/kg per minute for 1 minute, followed by maintenance infusion of 100 mcg/kg per minute for 4 minutes.

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.

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

Once the desired ventricular rate or a patient tolerance end point (e.g., reduction in BP) has been nearly achieved, 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.

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.

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

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.

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

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. 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.

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

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.

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.

Prescribing Limits

Adults

SVT

IV

Manufacturer recommends maximum maintenance dosage of 200 mcg/kg per minute. Maintenance dosages as high as 300 mcg/kg per minute have been used but provide little added benefit and increase the incidence of adverse effects. Safety of maintenance dosages >300 mcg/kg per minute not established.

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

Hypertension

Intraoperative and Postoperative Hypertension and/or Tachycardia

IV

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

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

Hypertensive Emergency

IV

Maximum 200 mcg/kg per minute.

Special Populations

Renal Impairment

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

Cautions for Esmolol

Contraindications

• Cardiogenic shock.

• Overt cardiac failure.

• Second- or third-degree AV block.

• Sinus bradycardia.

Warnings/Precautions

Warnings

Hypotension

Risk of hypotension, occasionally symptomatic (e.g., manifested as diaphoresis or dizziness). Can occur at any dose level but usually is dose related. Doses >200 mcg/kg per minute not recommended by manufacturer for SVT management.

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

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

Intraoperative or Postoperative Hypertension

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

Cardiac Failure

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

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

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

Bronchospastic Disease

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

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

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.

Use with caution in patients with diabetes mellitus or hypoglycemia.

General Precautions

Adverse effects generally resolve more rapidly than with other β-blockers because of esmolol’s short duration of action.

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.

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.

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

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.

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. 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.

Extravasation

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

Specific Populations

Pregnancy

Category C.

Lactation

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

Pediatric Use

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

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

Renal Impairment

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

Common Adverse Effects

Hypotension, dizziness, diaphoresis, headache, somnolence, confusion, agitation, nausea, infusion site reactions (e.g., inflammation, induration).

Drug Interactions

Specific Drugs

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.

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

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.

Distribution

Extent

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

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

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

Plasma Protein Binding

Esmolol: 55% (albumin and α₁-acid glycoprotein).

Metabolite (ASL 8123): Approximately 10%.

Elimination

Metabolism

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

Elimination Route

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

Half-life

Biphasic; distribution half-life of esmolol is about 2 minutes; terminal elimination half-life is about 9 minutes (range: 5–23 minutes).

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.

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

Stability

Storage

Parenteral

Injection

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

Compatibility

Parenteral

Solution CompatibilityHID

Drug Compatibility

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

Actions

• Selectively blocks cardiac β₁-adrenergic receptors with little effect on₂-adrenergic receptors of bronchial and vascular smooth muscle. At high doses (e.g., >300 mcg/kg per minute), selectivity usually diminishes and competitive inhibition of β₁- and β₂-adrenergic receptors occurs.

• Does not exhibit appreciable intrinsic sympathomimetic or membrane-stabilizing activity at usual clinical doses.

• Produces negative chronotropic and inotropic activity. Decreases resting and exercise-induced heart rate, reflex orthostatic tachycardia, myocardial contractility, rate of left ventricular pressure rise (dp/dt), right ventricular contractility, and cardiac index.

• Decreases SBP and DBP at rest and during exercise. May reduce BP by decreasing cardiac output, decreasing sympathetic outflow from the CNS, and/or suppressing renin release.

• Class II antiarrhythmic agent. Increases sinus cycle length, prolongs sinus node recovery time, and slows conduction in the AV node; apparently does not substantially affect sinoatrial conduction time, corrected sinus node recovery time, AV node refractoriness, retrograde AV nodal conduction time, or atrial, His-Purkinje, or ventricular conduction.

Advice to Patients

• Importance of informing clinicians of existing therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patient of other important precautionary information. (See Cautions.)

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

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