Esmolol hydrochloride

331.83

331.155029

1312995-182-4

DTXSID7049003

White or off-white crystalline powder|Crystals from methanol-ether

2922199090

67.8

2.72280

buffered aqueous solution

1.026

85-86 °C

430.2ºC at 760 mmHg

214ºC

H2O: soluble 12mg/mL

−20°C

In alcohol, 350 mg/l at room temperature|pKa = 9.5

Esmolol is related structurally to atenolol and metoprolol in that the drugs contain substitutents in the para position of benzene ring. /Esmolol/

NONH for all modes of transport

52/53

61

DA8346000

At a concentration of 10 mg/ml, esmolol hydrochloride is chemically and physically stable for at least 24 hours at 15-30 deg C or when refrigerated in the following IV solutions; 5% dextrose; 5% dextrose and Ringer's or lactated Ringer's, 5% dextrose and 0.45 or 0.9% sodium chloride; lactated Ringer's; or 0.45 or 0.9% sodium; or 5% dextrose and potassium chloride 40 mEq/l.

P305 + P351 + P338

H319

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

Esmolol, used as a cardiovascular drug, was approved by FDA for marketing in the United States on 12/31/86.|Esmolol, used as a beta adrenergic blocking agent, was approved by FDA for marketing in the United States 8/88.|The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl esmolol hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.|Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

|Danger|H301 (18.75%): Toxic if swallowed [Danger Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P310, P302+P352, P304+P340, P305+P351+P338, P311, P312, P321, P322, P330, P337+P313, P361, P363, P403+P233, P405, and P501|Aggregated GHS information provided by 48 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

When esmolol and a catecholamine-depleting drug (eg, reserpine) are administered concomitantly, the effects of the drugs may be additive.|Concomitant administration of esmolol and morphine in healthy adults resulted in about a 50% increase in steady-state blood esmolol concentrations, although the pharmacokinetics of morphine were not affected.|Esmolol may prolong the effects of succinylcholine, although the onset of neuromuscular blockade is not affected. Succinylcholine-induced neuromuscular blockade has been prolonged by about 60% during concomitant esmolol administration in some patients. ... In addition, the duration of neuromuscular blockade was not prolonged in other patients during concomitant therapy.|Blood esmolol concentration may be increased slightly during concomitant warfarin therapy ... .|For more Interactions (Complete) data for ESMOLOL HYDROCHLORIDE (11 total), please visit the HSDB record page.

LD50 Mice iv 93 mg/kg|LD50 Rat iv 71 mg/kg|LD50 Rabbit iv 40 mg/kg|LD50 Dogs iv 32 mg/kg|LD50 Mice iv 452 mg/kg /De-estrified metabolite (ASL 8123) of esmolol/

Adrenergic Beta-Antagonists|Esmolol is used IV principally to provide rapid, temporary control of ventricular rate in patients with supraventricular tachyarrhythmias (SVT) (eg, atrial flutter and/or fibrillation, sinus tachycardia).|Esmolol may be preferred to longer-acting B-adrenergic blocking agents for the short-term control of ventricular rate in patients with SVT because of the drug's rapid onset and short duration of effects, ... .|Esmolol is indicated for rapid and short-term control of ventricular rate in patients with atrial fibrillation or atrial flutter in perioperative, postoperative, or other emergency situations. It is also indicated in noncompensatory sinus tachycardia judged by the physician to need intervention. (Esmolol is used for control of heart rate in patients with myocardial ischemia. /NOT included in US product labeling/) It is not recommended for use in chronic situations where transfer to another agent is anticipated. /Included in US product labeling/|For more Therapeutic Uses (Complete) data for ESMOLOL HYDROCHLORIDE (6 total), please visit the HSDB record page.

Because of the risk of esmolol induced hypotension, blood pressure should be monitored closely during therapy with this drug, especially in patients with low pretreatment blood pressure (eg, systolic blood pressure less than 105 mm Hg). Hypotension can occur at any dose level with esmolol but usually is dose related, and doses exceeding 200 ug/kg per minute recommended by the manufacturer for the management of supraventricular tachyarrhythmias. Reversal of hypotension usually occurs within 30 minutes of discontinuing the drug or reducing the rate of IV infusion.|... Esmolol is contraindicated in patients with second- or third-degree atrioventricular blocks, sinus bradycardia, cardiogenic shock, or overt cardiac failure.|Esmolol may mask signs and symptoms of hypoglycemia (eg, tachycardia, palpitation, blood pressure changes, tremor, feelings of anxiety, but not sweating or dizziness) and may potentiate insulin-induced hypoglycemia; therefore, the drug should be used with caution in patients with diabetes mellitus or hypoglycemia.|Because of de-esterified metabolite (ASL 8123) of esmolol is eliminated mainly by the kidneys, ... the drug should be used with caution in patients with renal impairment, especially severe impairment.|For more Drug Warnings (Complete) data for ESMOLOL HYDROCHLORIDE (16 total), please visit the HSDB record page.

Drugs that bind to and block the activation of ADRENERGIC BETA-1 RECEPTORS. (See all compounds classified as Adrenergic beta-1 Receptor Antagonists.)

It is not known whether esmolol and/or ASL 8123 cross the placenta in humans, but the drug has been shown to cross the placenta in animals. In animals, fetal artery esmolol concentrations were about 10% of maternal concentrations at the completion of infusion. It also is not known whether esmolol and/or ASL 8123 are distributed into milk.|Following IV administration, esmolol is rapidly and widely distributed. The apparent volumes of distribution of esmolol and its de-esterifed metabolite (ASL 8123) in healthy adults are approximately 3.4 and 0.41 l/kg, respectively, following iv administration. In healthy adults, the volumes of distribution of esmolol in the central compartment and at steady state are approximately 0.87 and 1.2 l/kg, respectively, following IV administration. The apparent volume of distribution appears to be decreased in patients undergoing coronary artery bypass surgery and increased in patients with renal impairment undergoing peritoneal dialysis and in patients with liver cirrhosis.|Following IV administration in rats, esmolol is ditributed into liver and kidneys, but only minimally into CSF, spleen, or testes.|In vitro, esmolol is approximately 55% bound to plasma proteins, mainly albumin and alpha-1-acid glycoprotein. Protein binding of esmolol to alpha-1-acid glycoprotein does not appear to be concentration dependent at esmolol concentrations of 3-110 ug/ml. In vitro, ASL 8123 is approximately 10% bound to plasma proteins.|For more Absorption, Distribution and Excretion (Complete) data for ESMOLOL HYDROCHLORIDE (10 total), please visit the HSDB record page.

Esmolol is rapidly and extensively metabolized via esterases (probably arylesterase), principally in the cytosol of erythrocytes. Metabolism of the drug also may occur in highly perfused tissues that contain esterases (eg, liver, kidneys). Hydrolysis of the methyl ester moiety results in formation of the de-esterified (free acid) metabolite, 4-(2-hydroxy-3-((1-methylethyl)amino) propoxy)benzenepropanoic acid (ASL 8123), and methanol. Esmolol does not appear to be susceptible to hydrolysis via serum cholinesterase (pseudocholinesterase), acetylcholinesterase, or carbonic anhydrase. It is estimated that about 83% of an esmolol dose is metabolized to ASL 8123. ASL 8123 has a low affinity for beta-adrenergic receptors, exhibiting only minimal (about 1,000- to 1,500-fold less potent than esmolol) beta-blocking activity in animals and no appreciable blockade in humans. Unlike esmolol, ASL 8123 is eliminated principally by the kidneys, and the elimination half-life of the metabolite may be increased up to tenfold in patients with renal impairment; however, such accumulation is not thought to be clinically important since ASL 8123 has only minimal beta-blocking activity. The amount of methanol formed during hydrolysis of the drug does not appear to be clinically important. Following IV infusion of esmolol hydrochloride doses of 300 ug/kg per minute for up to l6 hours of 150 ug/kg per minute for 24 hours, blood methanol concentrations ranged from 2.8-5.9 or 2.9-13.2 ug/ml, respectively, being less than 2% of those usually associated with methanol toxicity.

Following IV infusion in adults, the half life of esmolol averages about 2 minutes in the initial distribution phase and about 9 minutes (range: 5-23 minutes) in the terminal elimination phase, although considerable interindividual variation in blood elimination half life exists.|Free acid metabolite: approx 3.7 hr (increased up to tenfold in renal failure)

Esmolol selectively inhibits response to adrenergic stimuli by competitively blocking cardiac B1-adrenergic receptors, while having little effect on the B2-adrenergic receptors of bronchial and vascular smooth muscle. At high doses (e.g., greater than 300 ug/kg per minute), this selectivity of esmolol for B1-adrenergic receptors usually diminishes, and the drug will competitively inhibit B1-and B2-adrenergic receptors.|By inhibiting myocardial beta1-adrenergic receptors, esmolol produces negative chronotropic and inotropic activity. Through its myocardial B1-adrenergic blocking action, esmolol 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.|The decrease in myocardial contractility, arterial pressure, and heart rate produced by esmolol can lead to a reduction in myocardial oxygen consumption, which may account for the effectiveness of the drug in myocardial ischemia.

Emergency and supportive measures. 1. Maintain an open airway and assist ventilation if necessary. 2. Treat coma, seizures, hypotension, hyperkalemia, and hypoglycemia if they occur. 3. Treat bradycardia with atropine, ... IV; isoproterenol ... ; or cardiac pacing. 4. Treat bronchospasm with nebulized bronchodilators. 5. Continuously monitor the vital signs and ECG for at least 6 hours after ingestion. /Esmolol, Beta-adrenergic blockers/|Specific drugs and antidotes. 1. Bradycardia and hypotension resistant to... /normal/ measures should be treated with glucagon, ... . Epinephrine (intravenous) infusion ... and titrating to effect. 2. Wide complex conduction deffects caused by membrane-depressant poisoning may respond to sodium bicarbonate, ... , as given for tricyclic antidepressant overdose. 3. Torsades de pointes polymorphous ventricular tachycardia associated with QT prolongation resulting from sotalol poisoning can be treated with isoproterenol infusion, magnesium, or overdrive pacing. Correction of hypokalemia may also be useful. /Esmolol, Beta-adrenergic blockers/|Decontamination. 1. Prehospital. Administer activated charcoal if available. 2. Hospital. Administer activated charcoal. Consider gastric lavage for large ingestions, especially involving propranolol. Gastric emptying is not necessary for small ingestions if activated charcoal can be given promptly. /Esmolol, Beta-adrenergic blockers/|/SRP:/ Basic treatment: Establish a patent airway. Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with normal saline during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poison A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

/SIGNS AND SYMPTOMS/ In general, overdosage of esmolol may be expected to produce effects that are mainly extensions of pharmacologic effects, particularly those involving the cardiovascular system. Overdosage of esmolol has resulted in cardiac arrest. As with other beta-adrenergic blocking agents, hypotension, symptomatic bradycardia, advanced AV block, intraventricular conduction defects, acute cardiac failure, seizures, and , in susceptible individuals, bronchospasm, hypoglycemia, electromechanical dissociation, and loss of consciousness might occur with esmolol overdosage. Cases of massive accidental overdosage of esmolol have occured because of errors in dilution. While some cases of overdosage have been fatal, others cases have resulted in permanent disability. Fatal overdosage has been associated with administration of a wide range of esmolol hydrochloride doses (0.625-2.5 g (12.5-50 mg/kg)). However, some patients have recovered completely from esmolol hydrochloride dose of up to 1.75 g given over 1 minute and from doses of 7.5 g given over 60 minutes during cardiovascular surgery. Generally, survival has occurred in those patients whose circulation could be supported while the effects of esmolol resolved.|/CASE REPORTS/ An infant was born to a woman who received intravenous esmolol for intrapartum supraventricular tachyarrhythmia. Despite the very short acting and cardio-selective beta-1 adrenergic blockade induced by that agent, neonatal effects can occur up to 48 hours after delivery.

ASL 8052

Parenteral concentrate, 250 mg/ml, for injection for IV infusion, Brevibloc (with alcohol 25% and propylene glycol 25%), Baxter; Injection, 10 mg/ml Brevibloc, Baxter|Brevibloc

Simple and rapid high-performance liquid chromatographic determination for esmolol in blood. The limit of detection was 5 ng/mL. The concn ranges 10-30,000 ng/ml. The mean abs and relative recoveries of esmolol from blood were 84 and 89%.|Analysis of esmolol in human blood by high-performance liquid chromatography and its application to pharmacokinetic studies monitored with UV-detection at 229 nm. The method has a detection limit of 0.025 ug esmolol/ml.|Liquid-chromatography analysis for esmolol and its metabolite in human urine monitored at 229 nm. The average extraction recoveries of esmolol and the metabolite were 95 and 92%, respectively. Relative std deviations for both cmpd were <6%.

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