Esmolol Hcl (esmolol HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Esmolol hydrochloride is a short-acting beta1-selective adrenergic blocking agent.
Esmolol is a short-acting beta1-selective adrenergic blocking agent that is structurally related to atenolol and metoprolol; the drug has pharmacologic actions similar to those of other beta-adrenergic blocking agents (beta-blockers). Esmolol selectively inhibits response to adrenergic stimuli by competitively blocking cardiac beta1-adrenergic receptors, while having little effect on the beta2-adrenergic receptors of bronchial and vascular smooth muscle. At high doses (e.g., greater than 300 mcg/kg per minute), this selectivity of esmolol for beta1-adrenergic receptors usually diminishes, and the drug will competitively inhibit beta1- and beta2-adrenergic receptors.
At usual clinical doses, esmolol does not exhibit appreciable intrinsic sympathomimetic or membrane-stabilizing activity, nor does the drug exhibit alpha-adrenergic blocking activity.
By inhibiting myocardial beta1-adrenergic receptors, esmolol produces negative chronotropic and inotropic activity. Through its myocardial beta1-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. Esmolol decreases systolic and diastolic blood pressure at rest and during exercise.
Esmolol exhibits antiarrhythmic activity and, like other beta-blockers, is considered a class II antiarrhythmic agent. Esmolol increases sinus cycle length, prolongs sinus node recovery time, and slows conduction in the atrioventricular (AV) node; ECG abnormalities manifested as Wenckebach period and prolongation of the AH interval during normal sinus rhythm and atrial pacing may result.
Steady-state blood esmolol concentrations are achieved within 30 minutes when the drug is infused IV at rates ranging from 50-400 mcg/kg per minute in healthy adults. Steady-state blood concentrations can be achieved more rapidly when a loading dose of the drug is injected initially. Following IV injection of a loading dose and then infusion of maintenance doses ranging from 50-300 mcg/kg per minute, steady-state blood concentrations of the drug are achieved within 5 minutes.
Steady-state blood esmolol concentrations reportedly increase proportionally with IV infusion rates ranging from 50-400 mcg/kg per minute. Because esmolol is hydrolyzed rapidly in blood, blood concentrations decline rapidly following discontinuance of IV infusions of the drug, with only negligible concentrations being present in blood 30 minutes after discontinuance.
Following rapid IV injection of 180 mg of esmolol hydrochloride in healthy exercising adults, a 13-18% decrease in heart rate, an 11-18% decrease in systolic blood pressure, and a 13-22% prolongation of the PR interval were evident within 1, 2, and 4 minutes, respectively. The time required to recover 50, 75, and 90% of the decrement in heart rate was 8, 10, and 13 minutes, respectively. Following IV infusion of maintenance esmolol hydrochloride doses of 25-300 mcg/kg per minute in patients with postoperative supraventricular tachyarrhythmias, a 15-20% decrease in heart rate was apparent within 5-22 minutes after initiation of the infusion.
After discontinuance of esmolol infusion, dissipation of beta-blockade is apparent within about 1-2 minutes, substantial recovery occurs within approximately 10-20 minutes, and complete reversal of beta-blockade occurs within 30 minutes. In vitro, esmolol is approximately 55% bound to plasma proteins, mainly albumin and alpha1-acid glycoprotein (alpha1-AGP); the acid metabolite is 10% bound to plasma protein. It is not known whether esmolol is distributed into milk.
Blood esmolol concentrations appear to decline in a biphasic manner following IV administration of the drug. Following IV infusion in adults, the half-life of esmolol averages about 2 minutes in the initial distribution phase (t1/2alpha) and about 9 minutes (range: 5-23 minutes) in the terminal elimination phase (t1/2beta), although considerable interindividual variation in blood elimination half-life exists. Because elimination of esmolol (but not its metabolites) occurs principally by nonrenal and nonhepatic means, it is not altered appreciably in patients with renal impairment, including those undergoing hemodialysis or peritoneal dialysis, nor in patients with hepatic impairment.
Esmolol is rapidly and extensively metabolized via esterases (probably arylesterase), principally in the cytosol of erythrocytes and not by plasma cholinesterases or red cell membrane acetylcholinesterase. Hydrolysis of the methyl ester moiety results in formation of the de-esterified (free acid) metabolite (ASL 8123) and methanol. It is estimated that about 83% of an esmolol dose is metabolized to ASL 8123.
The acid metabolite (ASL 8123) has a low affinity for beta-adrenergic receptors, exhibiting only minimal (about 1000- to 1500-fold less potent than esmolol) beta-blocking activity in animals and no appreciable blockade in humans; the metabolite elimination half-life is approximately 3.7 hours with an apparent renal clearance approximately equivalent to glomerular filtration rate (GFR). Unlike esmolol, ASL 8123 is eliminated principally by the kidneys, and the elimination half-life of the metabolite may be increased up to 12-fold (48 hours) in patients with end-stage renal disease; peak plasma concentrations are doubled; however, such accumulation is not thought to be clinically important since ASL 8123 has only minimal beta-blocking activity. Plasma concentrations of esmolol are similar in subjects with normal renal function and in patients with end stage renal disease on dialysis following a 4-hour maintenance infusion of esmolol hydrochloride 150 mcg/kg per minute.
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 mcg/kg per minute for up to 6 hours or 150 mcg/kg per minute for 24 hours, blood methanol concentrations approximated endogenous levels and were less than 2% of those usually associated with methanol toxicity. Following IV administration of esmolol hydrochloride, the drug is excreted principally in urine, mainly as the acid metabolite (ASL 8123).
About 73-88% of the drug is excreted as the acid metabolite (ASL 8123) and less than 2% as unchanged drug. Approximately 20% of an esmolol dose is removed as ASL 8123 by hemodialysis or by continuous ambulatory peritoneal dialysis; however, the amount of drug removed during dialysis depends on several factors (e.g., dialysis flow-rate, dwell time). In a small number of children 2-16 years of age with a history of supraventricular arrhythmias, pharmacokinetics were similar to that observed in adults.
Esmolol is used in the management of supraventricular tachycardias (SVTs) (e.g., atrial flutter and/or fibrillation, noncompensatory sinus tachycardia). Esmolol also is used in the management of hypertension associated with surgical events and in the management of hypertensive emergencies.
Generic name: esmolol HCl
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Esmolol Hcl
Indications
The following indications are listed for Esmolol Hcl:
- Perioperative Hypertension
- Perioperative Tachycardia
- Supraventricular Tachycardia
- Ventricular Rate Control In Atrial Fibrillation
Also known as: Paraoperative Tachycardia, Perioperative Polycardia, Perioperative Tachyarrhythmia, Perioperative Tachysystole, Supraventricular Polycardia, Supraventricular Tachyarrhythmia, Supraventricular Tachysystole.
Dosing
Esmolol is commercially available as esmolol hydrochloride; dosage is expressed in terms of the salt.
Dosage of esmolol hydrochloride must be adjusted carefully according to individual requirements, response, and tolerance. Patients should be monitored closely (e.g., blood pressure, respiratory rate, heart rate, ECG) during esmolol hydrochloride therapy. If adverse effects (e.g., hypotension, overt congestive heart failure, bradycardia) occur, the rate of infusion should be reduced or the infusion stopped as necessary.
Esmolol hydrochloride is administered by direct IV injection and continuous IV infusion.
Esmolol hydrochloride is commercially available as premixed solutions in ready-to-use bags for IV infusion and as a ready-to-use solution in single-dose vials for direct IV injection.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Esmolol hydrochloride is metabolized by red-blood cell esterases. Drug interactions with esmolol are primarily pharmacodynamic. The drug's effect on blood pressure, myocardial contractility, and electrical impulse propagation may result in severe hypotension, cardiac failure, severe bradycardia, sinus pause, sinoatrial block, atrioventricular block, and/or cardiac arrest when used in combination with other drugs that can lower blood pressure, reduce myocardial contractility, or interfere with sinus node function or electrical impulse propagation in the myocardium.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Hypersensitivity reactions, including anaphylaxis, to esmolol or any ingredient in the formulations; cross-sensitivity between beta-blockers is possible.
*Decompensated heart failure; may worsen heart failure.
*Cardiogenic shock: may precipitate further cardiovascular collapse or cause cardiac arrest.
*Pulmonary hypertension; may precipitate cardiorespiratory compromise.
*Administration of esmolol in close proximity (i.e., while cardiac effects from the other drug are still present) of IV calcium-channel blocking agents with cardiodepressant effects (e.g., verapamil); fatal cardiac arrests have occurred in patients receiving IV esmolol and IV verapamil.
*Severe sinus bradycardia; may precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest.
*Second- or third-degree AV block; may precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest.
*Sick sinus syndrome; may precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Most common adverse reactions to esmolol (>10%) are symptomatic hypotension (hyperhidrosis, dizziness) and asymptomatic hypotension.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Although safety and efficacy of esmolol remain to be established in pediatric patients, some experts have recommended pediatric dosages, preferably administered as a short-acting continuous infusion, for severe hypertension based on clinical experience. Esmolol may cause profound bradycardia when used for rapid reduction of blood pressure in pediatric patients with acute severe hypertension.+ In a small number of children 2-16 years of age with a history of supraventricular arrhythmias, pharmacokinetics were similar to that observed in adults.
Reproduction studies in rats and rabbits using esmolol hydrochloride doses up to 3 (10 times the maximum recommended human maintenance dose) and 1 mg/kg per minute, respectively, for 30 minutes daily, have not revealed evidence of maternal toxicity, embryotoxicity, or teratogenicity. However, esmolol hydrochloride doses of 10 mg/kg per minute produced maternal toxicity and death in rats, and doses of 2.5 mg/kg per minute produced minimal maternal toxicity and increased fetal resorptions in rabbits. Increased fetal resorptions with minimal maternal toxicity were also observed in rabbits given esmolol hydrochloride in doses approximately 8 times the maximum human maintenance dose (300 mcg/kg per minute).
There are no adequate and controlled studies to date using esmolol in pregnant women. Use of esmolol in the last trimester of pregnancy or during labor and delivery has been reported to cause fetal bradycardia, which continued after infusion of the drug was discontinued. Esmolol should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
It is not known whether esmolol hydrochloride is distributed into milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from IV esmolol hydrochloride, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
While clinical experience to date has not revealed age-related differences in response to esmolol hydrochloride, clinical studies evaluating the drug have not included sufficient numbers of adults 65 years of age or older to determine whether geriatric patients respond differently than younger adults. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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