Esmolol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as hydrochloride:

Brevibloc: 100 mg/10 mL (10 mL)

Brevibloc in NaCl: 2000 mg (100 mL); 2500 mg (250 mL)

Solution, Intravenous, as hydrochloride [preservative free]:

Brevibloc in NaCl: 2000 mg (100 mL); 2500 mg (250 mL) [latex free, pvc free]

Brevibloc Premixed: 2500 mg (250 mL) [latex free, pvc free]

Brevibloc Premixed DS: 2000 mg (100 mL) [latex free, pvc free]

Generic: 2000 mg (100 mL); 2500 mg (250 mL); 100 mg/10 mL (10 mL); 2500 mg/250 mL (250 mL); 2000 mg/100 mL (100 mL)

Pharmacology

Mechanism of Action

Class II antiarrhythmic: Competitively blocks response to beta₁-adrenergic stimulation with little or no effect of beta₂-receptors except at high doses, no intrinsic sympathomimetic activity, no membrane stabilizing activity

Pharmacokinetics/Pharmacodynamics

Distribution

V_d:

Children ≥2.5 years and Adolescents ≤16 years: 2 ± 1.4 L/kg (range: 0.5 to 3.6 L/kg) (Wiest 1991)

Adults: Esmolol: ~3.4 L/kg; Acid metabolite: ~0.4 L/kg

Metabolism

In blood by red blood cell esterases; forms acid metabolite (negligible activity; produces no clinically important effects) and methanol (does not achieve concentrations associated with methanol toxicity)

Excretion

Urine (~73% to 88% as acid metabolite, <2% unchanged drug)

Onset of Action

Beta-blockade: IV: 2-10 minutes (quickest when loading doses are administered)

Duration of Action

Hemodynamic effects: 10-30 minutes; prolonged following higher cumulative doses, extended duration of use

Half-Life Elimination

Children ≥18 months and Adolescents ≤16 years: Variable; mean range: 2.7 to 4.8 minutes (reported full range: 0.2 to 9.9 minutes) (Cuneo 1994; Tabbutt 2008; Wiest 1991; Wiest 1998)

Adults: Esmolol: 9 minutes; Acid metabolite: 3.7 hours; elimination of metabolite decreases with end-stage renal disease

Protein Binding

Esmolol: 55%; Acid metabolite: 10%

Use: Labeled Indications

Intraoperative and postoperative tachycardia and/or hypertension: Treatment of intraoperative and postoperative tachycardia and/or hypertension

Sinus tachycardia: Treatment of noncompensatory sinus tachycardia

Supraventricular tachycardia and atrial fibrillation/flutter: Control of ventricular rate in patients with supraventricular tachycardia or atrial fibrillation/flutter

Use: Off Label

Electroconvulsive therapy (attenuation of adrenergic response)cyes

Data from a small, double-blind, randomized block-design study in patients undergoing electroconvulsive therapy (ECT) demonstrated that pretreatment with esmolol or labetalol significantly reduced the hemodynamic response to ECT compared with fentanyl, lidocaine, or saline Weinger 1991. Additional trials may be necessary to further define the role of esmolol in this setting.

Based on the American Psychiatric Association practice guideline for the treatment of patients with major depressive disorder (3rd edition), the use of short-acting beta-blockers at the time of ECT is a recommended treatment to control the cardiovascular side effects caused by ECT.

Hypertensive emergenciescyes

Severe hypertension associated with an acute MI may be treated with esmolol to reduce the underlying coronary ischemia and/or increased myocardial oxygen consumption and to improve prognosis. Severe hypertension associated with aortic dissection may be treated with esmolol to lessen pulsatile load or aortic stress by lowering the blood pressure in order to retard the propagation of the dissection and prevent aortic rupture Papadopoulos 2015, Rhoney 2009.

Based on the 2015 American Heart Association/American College of Cardiology/American Society of Hypertension (AHA/ACC/ASH) scientific statement regarding the treatment of hypertension in patients with coronary artery disease (CAD), esmolol can be considered in patients with severe hypertension or ongoing ischemia who are hemodynamically stable without decompensated heart failure. Based on the 2017 American College of Cardiology American Heart Association Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults, esmolol is a preferred agent for patients with hypertensive emergency and acute aortic dissection, acute coronary syndrome, or in the perioperative setting ACC/AHA [Whelton 2017].

Intubation (attenuation of adrenergic response)a

In a randomized, double-blind study in patients undergoing laryngoscopy and tracheal intubation at risk for tachycardia, hypertension, and myocardial ischemia triggered by intubation, patients who were pretreated with esmolol had significantly lower heart rate and rate-pressure product than control Ugur 2007. In a randomized, double-blind study of isolated head trauma patients, pretreatment with esmolol had similar efficacy in reducing heart rate and blood pressure during intubation as compared to lidocaine Levitt 2001. In a randomized, double-blind, placebo-controlled study in patients undergoing elective gynecologic procedures with general anesthesia requiring intubation, esmolol monotherapy was effective in attenuating heart rate response, neither esmolol nor lidocaine monotherapy affected blood pressure response, and the combination of esmolol and lidocaine attenuated both heart rate and blood pressure response Kindler 1996.

Thyroid stormyes

Based on the 2016 American Thyroid Association guidelines for the diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis, beta-blockade with esmolol as part of a multimodality approach is effective and recommended in the treatment of thyroid storm.

Thyrotoxicosisyes

Based on the 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis, beta-blockers, including esmolol, are effective and recommended in the treatment of symptomatic thyrotoxicosis Ross 2016.

Ventricular tachycardiayes

Based on the American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guideline for management of patients with ventricular arrhythmias and prevention of sudden cardiac death, beta-blockers are effective for control of ventricular tachycardia.

Contraindications

Hypersensitivity to esmolol or any component of the formulation; severe sinus bradycardia; heart block greater than first degree (except in patients with a functioning artificial ventricular pacemaker); sick sinus syndrome; cardiogenic shock; decompensated heart failure; IV administration of calcium channel blockers (eg, verapamil) in close proximity to esmolol (ie, while cardiac effects of other drug are still present); pulmonary hypertension

Documentation of allergenic cross-reactivity for beta-blockers is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in US labeling): Patients requiring inotropic agents and/or vasopressors to maintain cardiac output and systolic blood pressure; hypotension; right ventricular failure secondary to pulmonary hypertension; untreated pheochromocytoma

Dosage and Administration

Dosing: Adult

Intraoperative and postoperative tachycardia and/or hypertension: IV:

Immediate control: Initial bolus: 1,000 mcg/kg over 30 seconds, followed by a 150 mcg/kg/minute infusion, if necessary. Adjust infusion rate as needed to maintain desired heart rate and/or blood pressure (up to 300 mcg/kg/minute).

Gradual control: Initial bolus: 500 mcg/kg over 1 minute, followed by a 50 mcg/kg/minute infusion for 4 minutes. Infusion may be continued at 50 mcg/kg/minute or, if the response is inadequate, titrated upward in 50 mcg/kg/minute increments (increased no more frequently than every 4 minutes) to a maximum of 300 mcg/kg/minute; may administer an optional loading dose equal to the initial bolus (500 mcg/kg over 1 minute) prior to each increase in infusion rate.

For control of tachycardia, doses >200 mcg/kg/minute provide minimal additional effect. For control of postoperative hypertension, as many as one-third of patients may require higher doses (250 to 300 mcg/kg/minute) to control blood pressure; the safety of doses >300 mcg/kg/minute has not been studied.

Hypertensive emergencies (off-label use): IV: Loading dose: 500 to 1,000 mcg/kg over 1 minute, followed by a 50 mcg/kg/minute infusion. For additional blood pressure control, repeat loading dose and increase infusion by 50 mcg/kg/minute increments up to a maximum dose of 200 mcg/kg/minute (ACC/AHA [Whelton 2017]).

Supraventricular tachycardia and atrial fibrillation/flutter or noncompensatory sinus tachycardia: IV: Loading dose (optional): 500 mcg/kg over 1 minute; follow with a 50 mcg/kg/minute infusion for 4 minutes; response to this initial infusion rate may be a rough indication of the responsiveness of the ventricular rate.

Infusion may be continued at 50 mcg/kg/minute or, if the response is inadequate, titrated upward in 50 mcg/kg/minute increments (increased no more frequently than every 4 minutes) to a maximum of 200 mcg/kg/minute.

To achieve more rapid response, following the initial loading dose and 50 mcg/kg/minute infusion, rebolus with a second 500 mcg/kg loading dose over 1 minute, and increase the maintenance infusion to 100 mcg/kg/minute for 4 minutes. If necessary, a third (and final) 500 mcg/kg loading dose may be administered, prior to increasing to an infusion rate of 150 mcg/kg/minute. After 4 minutes of the 150 mcg/kg/minute infusion, the infusion rate may be increased to a maximum rate of 200 mcg/kg/minute (without a bolus dose). The ACC/AHA/HRS supraventricular tachycardia guidelines recommend a maximum dose of 300 mcg/kg/minute (ACC/AHA/HRS [Page 2016]).

Note: If a loading dose is not administered, a continuous infusion at a fixed dose reaches steady-state in ~30 minutes. In general, the usual effective dose is 50 to 200 mcg/kg/minute; doses as low as 25 mcg/kg/minute may be adequate. Maintenance infusions may be continued for up to 48 hours.

Electroconvulsive therapy (off-label use): IV: 1,000 mcg/kg administered 1 minute prior to induction of anesthesia (Weinger 1991)

Intubation (off-label use): IV: 1,000 to 2,000 mcg/kg given 1.5 to 3 minutes prior to intubation (Kindler 1996; Levitt 2001; Ugur 2007)

Thyrotoxicosis or thyroid storm (off-label use): IV: 50 to 100 mcg/kg/minute (Ross 2016)

Ventricular tachycardia (off-label use): IV: 500 mcg/kg bolus followed by 50 mcg/kg/minute (AHA/ACC/HRS [Al-Khatib 2017])

Guidelines for transfer to oral therapy (beta-blocker, calcium channel blocker):

Infusion should be reduced by 50% thirty minutes following the first dose of the alternative agent

Manufacturer suggests following the second dose of the alternative drug, patient's response should be monitored and if control is adequate for the first hour, esmolol may be discontinued.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dose must be titrated to individual response and tolerance.

Hypertensive emergency/urgency: Infants, Children, and Adolescents: Continuous IV infusion: 100 to 500 mcg/kg/minute infusion (NHBPEP Working Group 2004); another approach is to initiate therapy with a bolus of 100 to 500 mcg/kg over 1 minute, followed by an infusion of 25 to 100 mcg/kg/minute; titrating as needed up to 500 mcg/kg/minute (Chandar 2012; Temple 2000)

Postoperative hypertension: Limited data available; large effective dose range reported: Infants and Children: Initial IV bolus: 100 to 500 mcg/kg, followed by continuous IV infusion: Initial rate: 100 to 500 mcg/kg/minute; titrate to effect; range of effective doses: 125 to 1,000 mcg/kg/minute (Tabbutt 2008a; Tabbutt 2008b; Wiest 1998). Dosing based on several trials. In the largest trial, patients (n=118, weight ≥2.5 kg, age <6 years, mean age: ~18 months) experiencing hypertension after coarctation of aorta repair received a median maximum dose of 521 mcg/kg/minute (Tabbutt 2008b); the need for coadministration of nitroprusside infusion increased with patient age (age ≤30 days: 27%, >30 days to <2 years: 54%; age 2 to 6 years: 69%). In a smaller trial (n=20, age: 1 month to 12 years, median age: 25.6 months), patients experiencing hypertension after heart surgery (including 10 with coarctation of the aorta) a higher mean effective dose of 700 mcg/kg/minute was reported. In this trial, infants were initiated at 100 mcg/kg/minute, then titrated by 50 mcg/kg/minute every 10 minutes; patients with aortic coarctation repair required a significantly higher dose (mean: 830 ± 153 mcg/kg/minute) than patients with repair of other congenital heart defects (mean: 570 ± 230 mcg/kg/minute) (Wiest 1998).

Supraventricular tachycardia (SVT): Limited data available: Children and Adolescents: Initial IV bolus: 100 to 500 mcg/kg over 1 minute followed by a continuous IV infusion: Initial rate: 25 to 100 mcg/kg/minute, titrate in 25 to 50 mcg/kg/minute increments; usual maintenance dose: 50 to 500 mcg/kg/minute (Park 2014); doses up to 1,000 mcg/kg/minute have been reported (Trippel 1991). One electrophysiologic study assessing esmolol-induced beta-blockade (n=20, age range: 2 to 16 years) used an initial dose of 600 mcg/kg over 2 minutes followed by an infusion of 200 mcg/kg/minute; the infusion was titrated upward by 50 to 100 mcg/kg/minute every 5 to 10 minutes until a reduction >10% in heart rate or mean blood pressure occurred. Mean dose required: 550 mcg/kg/minute with a range of 300 to 1,000 mcg/kg/minute (Trippel 1991).

Administration

IV: Loading doses may be administered over 30 seconds to 1 minute depending on how urgent the need for effect. Infusion into small veins or through a butterfly catheter should be avoided (can cause thrombophlebitis). Medication port of premixed bags should be used to withdraw only the initial bolus, if necessary (not to be used for withdrawal of additional bolus doses).

Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze. Protect from excessive heat. Stable for at least 24 hours (under refrigeration or at controlled room temperature) at a final concentration of 10 mg/mL in D5W, D5LR, D5R, D5¹/₂NS, D5NS, LR, ¹/₂NS, or NS.

Drug Interactions

Acetylcholinesterase Inhibitors: May enhance the bradycardic effect of Beta-Blockers. Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

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

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

Barbiturates: May decrease the serum concentration of Beta-Blockers. Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Benperidol: 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

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Bromperidol: Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination

Bupivacaine: Beta-Blockers may increase the serum concentration of Bupivacaine. Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): May enhance the bradycardic effect of Esmolol. Management: Administration of IV verapamil or diltiazem together with esmolol is contraindicated if one agent is given while the effects of the other are still present. Canadian esmolol labeling specifies that use within 24 hours is contraindicated. Consider therapy modification

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. Exceptions are discussed in separate monographs. Consider therapy modification

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. Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. 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

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy

EPINEPHrine (Nasal): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Nasal). Monitor therapy

EPINEPHrine (Oral Inhalation): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Oral Inhalation). Monitor therapy

Epinephrine (Racemic): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of Epinephrine (Racemic). Monitor therapy

EPINEPHrine (Systemic): Beta-Blockers (Beta1 Selective) may diminish the therapeutic effect of EPINEPHrine (Systemic). Monitor therapy

Ergot Derivatives: Beta-Blockers may enhance the vasoconstricting effect of Ergot Derivatives. Exceptions: Nicergoline. Consider therapy modification

Fexinidazole [INT]: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole [INT]. Avoid combination

Fingolimod: Esmolol may enhance the bradycardic effect of Fingolimod. Avoid combination

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

Insulins: Beta-Blockers may enhance the hypoglycemic effect of Insulins. 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

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. 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

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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. Monitor therapy

Methoxyflurane: May enhance the hypotensive effect of Beta-Blockers. Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Morphine (Systemic): May increase the serum concentration of Esmolol. 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

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. 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

Opioids (Anilidopiperidine): May enhance the bradycardic effect of Beta-Blockers. Opioids (Anilidopiperidine) may enhance the hypotensive effect of Beta-Blockers. Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. 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

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. Consider therapy modification

Succinylcholine: Esmolol may enhance the neuromuscular-blocking effect of Succinylcholine. 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

Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing 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

Adverse Reactions

>10%: Cardiovascular: Asymptomatic hypotension (25%), symptomatic hypotension (12%)

1% to 10%:

Cardiovascular: Peripheral ischemia (1%)

Central nervous system: Dizziness (≤3%), drowsiness (3%), headache (2%), agitation (≤2%), confusion (≤2%)

Gastrointestinal: Nausea (7%), vomiting (1%)

Local: Infusion site reaction (8%; including inflammation and induration)

<1%, postmarketing, and/or case reports: Abdominal distress, abnormality in thinking, angioedema, anxiety, bradycardia, constipation, coronary artery vasospasm, depression, dyspepsia, flushing, heart block, hyperkalemia, increased heart rate (moderate increase above pretreatment levels 30 minutes after discontinuation), infusion site irritation, local thrombophlebitis (at infusion site), local tissue necrosis (at infusion site), pallor, paresthesia, psoriasis, renal tubular acidosis (hyperkalemic), seizure, severe bradycardia, sinus pause, skin blister (at infusion site), syncope, urinary retention, urticaria, voice disorder, xerostomia

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactic reactions: Use caution with history of severe anaphylaxis to allergens; patients taking beta-blockers may become more sensitive to repeated challenges. Treatment of anaphylaxis (eg, epinephrine) in patients taking beta-blockers may be ineffective or promote undesirable effects.
• Extravasation: Vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. Extravasation can lead to skin necrosis and sloughing; avoid infusions into small veins or through a butterfly catheter.
• Hyperkalemia: Esmolol has been associated with elevations in serum potassium and development of hyperkalemia especially in patients with risk factors (eg, renal impairment); monitor serum potassium during therapy.
• Hypotension: Can commonly occur; patients need close blood pressure monitoring. If an unacceptable drop in blood pressure occurs, reduction in dose or discontinuation may reverse hypotension (usually within 30 minutes).

Disease-related concerns:

• Bronchospastic disease: In general, patients with bronchospastic disease should not receive beta-blockers; however, esmolol, with B₁ selectivity, has been used cautiously with close monitoring.
• Conduction abnormality: Can cause bradycardia including sinus pause, heart block, severe bradycardia, and cardiac arrest. Consider preexisting conditions such as first degree AV block, sick sinus syndrome, or other conduction disorders before initiating; use is contraindicated in patients with sick sinus syndrome or second- or third-degree AV block (except in patients with a functioning artificial ventricular pacemaker).
• Diabetes: Use with caution in patients with diabetes mellitus; may potentiate hypoglycemia and/or mask signs and symptoms.
• Heart failure (HF): Use with caution in patients with compensated heart failure and monitor for a worsening of the condition. Use is contraindicated in patients with decompensated heart failure.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis.
• Peripheral vascular disease (PVD) and Raynaud disease: Can 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.
• Renal impairment: Use with caution in patients with renal impairment; active metabolite retained.
• 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.

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.

Special populations:

• Elderly: Bradycardia may be observed more frequently in elderly patients (>65 years of age); dosage reductions may be necessary.

Other warnings/precautions:

• Abrupt withdrawal: Beta-blocker therapy should not be withdrawn abruptly (particularly in patients with CAD), but gradually tapered 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.
• Hypertension associated with hypothermia: Use esmolol with caution in patients with hypertension associated with hypothermia; monitor vital signs closely and titrate esmolol slowly.
• Hypovolemic patients: Avoid use in patients with hypovolemia; treat hypovolemia first, otherwise, use of esmolol may attenuate reflex tachycardia and further increase the risk of hypotension.

Monitoring Parameters

Blood pressure, MAP, heart rate, continuous ECG, respiratory rate, IV site; serum potassium (especially with renal impairment); consult individual institutional policies and procedures

Pregnancy

Pregnancy Considerations

Exposure to esmolol may cause fetal bradycardia which may continue after esmolol is discontinued. If maternal use of a beta-blocker is needed, fetal growth should be monitored during pregnancy and the newborn should be monitored for 48 hours after delivery for bradycardia, hypoglycemia, and respiratory depression (ESC [Regitz-Zagrosek 2018]).

Esmolol is a short-acting beta-blocker and not indicated for the chronic treatment of hypertension; however, use may be considered as an alternative agent for hypertensive emergencies in pregnancy (ACOG 767 2019). Agents other than esmolol may be preferred for the treatment of supraventricular tachycardia, atrial fibrillation, atrial flutter, and ventricular tachycardia in pregnancy. Consult current guidelines for indication specific recommendations (ACC/AHA/HRS [Page 2016]; ESC [Regitz-Zagrosek 2018]).

Patient Education

What is this drug used for?

• It is used to treat a fast heartbeat.
• It is used to treat high blood pressure.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• High potassium like abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling.
• Acidosis like confusion, fast breathing, fast heartbeat, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy.
• Dizziness
• Passing out
• Sweating a lot
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Slow heartbeat
• Abnormal heartbeat
• Injection site burning, redness, pain, edema, or severe irritation
• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.