View source for Esmolol

{{DrugProjectFormSinglePage
|authorTag={{AZ}}; {{AK}}; {{Alonso}}
|genericName=Esmolol
|aOrAn=a
|drugClass=beta-adrenergic blocker
|indication=[[supraventricular tachycardia]]or noncompensatory [[sinus tachycardia]], intraoperative and postoperative [[tachycardia]] and/or [[hypertension]]
|adverseReactions=hypotension, injection site pain, nausea
|blackBoxWarningTitle=Warning Title
|blackBoxWarningBody=<i><span style="color:#FF0000;">Condition Name:</span></i> (Content)
|fdaLIADAdult======Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia=====

* Dosing Information

:*  Esmolol is administered by continuous intravenous infusion with or without a loading dose. Additional loading doses and/or titration of the maintenance infusion (step-wise dosing) may be necessary based on desired ventricular response. 

[[File:Stepwise esmolol dosing.JPG|800px|thumbnail|left|This image is provided by the National Library of Medicine.]]
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:* In the absence of loading doses, continuous infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes.
:* The effective maintenance dose for continuous and step-wise dosing is 50 to 200 mcg per kg per minute, although doses as low as 25 mcg per kg per minute have been adequate. Dosages greater than 200 mcg per kg per minute provide little added heart rate lowering effect, and the rate of adverse reactions increases.
:* Maintenance infusions may be continued for up to 48 hours.

=====Intraoperative and Postoperative Tachycardia and Hypertension=====

* Dosing Information

:* In this setting it is not always advisable to slowly titrate to a therapeutic effect. Therefore two dosing options are presented:  immediate control and gradual control.

======Immediate Control======

* Administer 1 mg per kg as a bolus dose over 30 seconds followed by an infusion of 150 mcg per kg per min if necessary.
* Adjust the infusion rate as required to maintain desired heart rate and blood pressure. Refer to Maximum Recommended Doses below.

======Gradual Control======

* Administer 500 mcg per kg as a bolus dose over 1 minute followed by a maintenance infusion of 50 mcg per kg per min for 4 minutes.
* Depending on the response obtained, continue dosing as outlined for supraventricular tachycardia. Refer to Maximum Recommended Doses below.

======Maximum Recommended Doses======

* For the treatment of tachycardia, maintenance infusion dosages greater than 200 mcg per kg per min are not recommended; dosages greater than 200 mcg per kg per min provide little additional heart rate-lowering effect, and the rate of adverse reactions increases.
* For the treatment of hypertension, higher maintenance infusion dosages (250-300 mcg per kg per min) may be required. The safety of doses above 300 mcg per kg per minute has not been studied.

======Transition from esmolol Injection Therapy to Alternative Drugs======

* After patients achieve adequate control of the heart rate and a stable clinical status, transition to alternative antiarrhythmic drugs may be accomplished.
* When transitioning from esmolol to alternative drugs, the physician should carefully consider the labeling instructions of the alternative drug selected and reduce the dosage of esmolol as follows:
:* Thirty minutes following the first dose of the alternative drug, reduce the esmolol infusion rate by one-half (50%).
:* After administration of the second dose of the alternative drug, monitor the patient’s response and if satisfactory control is maintained for the first hour, discontinue the esmolol infusion.

=====Directions for Use=====

* Esmolol injection is available in a pre-mixed bag and ready-to-use vial. Esmolol is not compatible with [[Sodium Bicarbonate]] (5%) solution (limited stability) or [[furosemide]] (precipitation).
* Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

'''''Premixed Bag'''''

* The medication port is to be used solely for withdrawing an initial bolus from the bag.
* Use aseptic technique when withdrawing the bolus dose.
* Do not add any additional medications to the bag.

[[File:Two port esmolol ba.JPG|800px|thumbnail|left|This image is provided by the National Library of Medicine.]]
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'''''Ready-to-Use Vial'''''

* The Ready-to-use Vial may be used to administer a loading dosage by hand-held syringe while the maintenance infusion is being prepared.
|offLabelAdultGuideSupport======Condition 1=====

* Developed by: (Organisation)

* Class of Recommendation: (Class) (Link)

* Strength of Evidence: (Category A/B/C) (Link)

* Dosing Information/Recommendation

:* (Dosage)

=====Condition 2=====

* Developed by: (Organisation)

* Class of Recommendation: (Class) (Link)

* Strength of Evidence: (Category A/B/C) (Link)

* Dosing Information/Recommendation

:* (Dosage)
|offLabelAdultNoGuideSupport======Condition 1=====

* Dosing Information

:* (Dosage)

=====Condition 2=====

* Dosing Information

:* (Dosage)

=====Condition 3=====

* Dosing Information

:* (Dosage)
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Esmolol in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Esmolol in pediatric patients.
|contraindications=Esmolol is contraindicated in patients with:
* Severe [[sinus bradycardia]]:  May precipitate or worsen [[bradycardia]] resulting in [[cardiogenic shock]] and [[cardiac arrest]].
* [[Heart block]] greater than first degree:  Second- or third-degree atrioventricular 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]].
* Decompensated [[heart failure]]:  May worsen [[heart failure]].
* [[Cardiogenic shock]]:  May precipitate further cardiovascular collapse and cause [[cardiac arrest]].
* IV administration of cardiodepressant [[calcium channel blockers]] (e.g., [[verapamil]]) and esmolol in close proximity (i.e., while cardiac effects from the other are still present); fatal [[cardiac arrests]] have occurred in patients receiving esmolol and intravenous [[verapamil]].
* [[Pulmonary hypertension]]:  May precipitate cardiorespiratory compromise.
* [[Hypersensitivity]] reactions, including [[anaphylaxis]] to esmolol or any of the inactive ingredients of the product (cross-sensitivity between [[beta blockers]] is possible).
|warnings======Hypotension=====

[[Hypotension]] can occur at any dose but is dose-related. Patients with hemodynamic compromise or on interacting medications are at particular risk. Severe reactions may include loss of consciousness, cardiac arrest, and death. For control of ventricular [[heart rate]], maintenance doses greater than 200 mcg per kg per min are not recommended. Monitor patients closely, especially if pretreatment blood pressure is low. In case of an unacceptable drop in [[blood pressure]], reduce or stop esmolol injection. Decrease of dose or termination of infusion reverses [[hypotension]], usually within 30 minutes.

=====Bradycardia=====

[[Bradycardia]], including sinus pause, [[heart block]], severe [[bradycardia]], and [[cardiac arrest]] have occurred with the use of esmolol injection. Patients with first-degree [[atrioventricular block]], sinus node dysfunction, or conduction disorders may be at increased risk. Monitor heart rate and rhythm in patients receiving esmolol.

If severe [[bradycardia]] develops, reduce or stop esmolol.

=====Cardiac Failure=====

[[Beta blockers]], like esmolol injection, can cause depression of myocardial contractility and may precipitate [[heart failure]] and [[cardiogenic shock]]. At the first sign or symptom of impending [[cardiac failure]], stop esmolol and start supportive therapy.

=====Intraoperative and Postoperative Tachycardia and/or Hypertension=====

Monitor vital signs closely and titrate esmolol slowly in the treatment of patients whose [[blood pressure]] is primarily driven by vasoconstriction associated with [[hypothermia]].

=====Reactive Airways Disease=====

Patients with reactive airways disease should, in general, not receive [[beta blockers]]. Because of its relative beta1 selectivity and titratability, titrate esmolol to the lowest possible effective dose. In the event of [[bronchospasm]], stop the infusion immediately; a beta2 stimulating agent may be administered with appropriate monitoring of ventricular rates.

=====Use in Patients with Diabetes Mellitus and Hypoglycemia=====

In patients with [[hypoglycemia]], or diabetic patients (especially those with labile diabetes) who are receiving [[insulin]] or other [[hypoglycemic agents]], [[beta blockers]] may mask [[tachycardia]] occurring with [[hypoglycemia]], but other manifestations such as [[dizziness]] and sweating may not be masked.

Concomitant use of beta blockers and antidiabetic agents can enhance the effect of antidiabetic agents (blood glucose–lowering).

=====Infusion Site Reactions=====

Infusion site reactions have occurred with the use of esmolol injection. They include irritation, inflammation, and severe reactions ([[thrombophlebitis]], [[necrosis]], and [[blistering]]), in particular when associated with extravasation. Avoid infusions into small veins or through a butterfly catheter.

If a local infusion site reaction develops, use an alternative infusion site and avoid extravasation.

=====Use in Patients with Prinzmetal's Angina=====

Beta blockers may exacerbate anginal attacks in patients with [[Prinzmetal’s angina]] because of unopposed alpha receptor–mediated coronary artery vasoconstriction. Do not use nonselective [[beta blockers]].

=====Use in Patients with Pheochromocytoma=====

If esmolol is used in the setting of [[pheochromocytoma]], give it in combination with an [[alpha-blocker]], and only after the [[alpha-blocker]] has been initiated. Administration of [[beta-blockers]] alone in the setting of [[pheochromocytoma]] has been associated with a paradoxical increase in [[blood pressure]] from the attenuation of beta-mediated vasodilation in skeletal muscle.

=====Use in Hypovolemic Patients=====

In hypovolemic patients, esmolol injection can attenuate reflex [[tachycardia]] and increase the risk of [[hypotension]].

=====Use in Patients with Peripheral Circulatory Disorders=====

In patients with peripheral circulatory disorders (including [[Raynaud’s disease]] or syndrome, and peripheral occlusive vascular disease), esmolol may aggravate peripheral circulatory disorders.

=====Abrupt Discontinuation of esmolol Injection=====

Severe exacerbations of [[angina]], [[myocardial infarction]], and ventricular [[arrhythmias]] have been reported in patients with [[coronary artery disease]] upon abrupt discontinuation of beta blocker therapy. Observe patients for signs of [[myocardial ischemia]] when discontinuing esmolol.

[[Heart rate]] increases moderately above pretreatment levels 30 minutes after esmolol discontinuation.

=====Hyperkalemia=====

Beta blockers, including esmolol, have been associated with increases in serum [[potassium]] levels and [[hyperkalemia]]. The risk is increased in patients with risk factors such as [[renal impairment]]. Intravenous administration of [[beta blocker]]s has been reported to cause potentially life-threatening [[hyperkalemia]] in [[hemodialysis]] patients. Monitor serum electrolytes during therapy with esmolol.

=====Use in Patients with Metabolic Acidosis=====

Beta blockers, including esmolol, have been reported to cause hyperkalemic [[renal tubular acidosis]]. Acidosis in general may be associated with reduced cardiac contractility.

=====Use in Patients with Hyperthyroidism=====

Beta-adrenergic blockade may mask certain clinical signs (e.g., [[tachycardia]]) of [[hyperthyroidism]]. Abrupt withdrawal of beta blockade might precipitate a [[thyroid storm]]; therefore, monitor patients for signs of [[thyrotoxicosis]] when withdrawing beta blocking therapy.

=====Use in Patients at Risk of Severe Acute Hypersensitivity Reactions=====

When using [[beta blockers]], patients at risk of [[anaphylactic]] reactions may be more reactive to [[allergen]] exposure (accidental, diagnostic, or therapeutic).

Patients using [[beta blockers]] may be unresponsive to the usual doses of epinephrine used to treat [[anaphylactic]] or [[anaphylactoid]] reactions.
|clinicalTrials======Clinical Trials Experience=====

* Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
* The following adverse reaction rates are based on use of esmolol in clinical trials involving 369 patients with [[supraventricular tachycardia]] and over 600 intraoperative and postoperative patients enrolled in clinical trials. Most adverse effects observed in controlled clinical trial settings have been mild and transient. The most important and common adverse effect has been [[hypotension]]. Deaths have been reported in post-marketing experience occurring during complex clinical states where esmolol was presumably being used simply to control ventricular rate

[[File:Esmololclinicaltrialsadverse.JPG|800px|thumbnail|left|This image is provided by the National Library of Medicine.]]
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=====Clinical Trial Adverse Reactions (Frequency <3%)=====
======Psychiatric Disorders======
* [[Confusion]]al state and [[agitation]] (~2%)
* [[Anxiety]], [[depression]] and abnormal thinking (<1%)

======Nervous System Disorders======
* [[Headache]] (~ 2%)
* [[Paresthesia]], [[syncope]], [[speech disorder]], and [[lightheadedness ]] (<1%)
* Convulsions (<1%), with one death

======Vascular Disorders======
* [[Peripheral ischemia]] (~1%)
* [[Pallor]] and [[flushing]] (<1%)

======Gastrointestinal Disorders======
* [[Vomiting]] (~1%)
* [[Dyspepsia]], [[constipation]], [[dry mouth]], and [[abdominal discomfort]] (<1%)

======Renal and Urinary Disorders======
* [[Urinary retention]] (<1%)
|postmarketing=In addition to the adverse reactions reported in clinical trials, the following adverse reactions have been reported in the post-marketing experience. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or to establish a causal relationship to drug exposure.

===Cardiac Disorders===
* [[Cardiac arrest]], Coronary arteriospasm

===Skin and Subcutaneous Tissue Disorders===
* [[Angioedema]], [[Urticaria]], [[Psoriasis]]
|drugInteractions=Concomitant use of esmolol injection with other drugs that can lower [[blood pressure]], reduce myocardial contractility, or interfere with [[sinus node]] function or electrical impulse propagation in the [[myocardium]] can exaggerate esmolol's effects on [[blood pressure]], contractility, and impulse propagation. Severe interactions with such drugs can result in, for example, severe [[hypotension]], [[cardiac failure]], severe [[bradycardia]], sinus pause, [[sinoatrial block]], [[atrioventricular block]], and/or [[cardiac arrest]]. In addition, with some drugs, beta blockade may precipitate increased withdrawal effects (e.g. [[clonidine]], [[guanfacine]], and [[monoxide]]). Esmolol should therefore be used only after careful individual assessment of the risks and expected benefits in patients receiving drugs that can cause these types of pharmacodynamic interactions, including but not limited to:
* [[Digitalis glycosides]]:  Concomitant administration of [[digoxin]] and esmolol leads to an approximate 10% to 20% increase of [[digoxin]] blood levels at some time points. [[Digoxin]] does not affect esmolol pharmacokinetics. Both [[digoxin]] and beta blockers slow atrioventricular conduction and decrease the heart rate. Concomitant use increases the risk of [[bradycardia]].
* [[Anticholinesterases]]:  esmolol prolonged the duration of [[succinylcholine]]-induced neuromuscular blockade and moderately prolonged clinical duration and recovery index of [[mivacurium]].
* Antihypertensive agents [[clonidine]], [[guanfacine]], or [[moxonidine]]:  [[Beta blockers]] also increase the risk of [[clonidine]]-, [[guanfacine]]-, or [[moxonidine]]-withdrawal rebound [[hypertension]]. If, during concomitant use of a [[beta blocker]], antihypertensive therapy needs to be interrupted or discontinued, discontinue the [[beta blocker]] first, and the discontinuation should be gradual.
* [[Calcium channel antagonists]]:  In patients with depressed myocardial function, use of esmolol with cardiodepressant [[calcium channel antagonists]] (e.g., [[verapamil]]) can lead to fatal cardiac arrests.
* [[Sympathomimetic]] drugs:  Sympathomimetic drugs having [[beta-adrenergic agonist]] activity will counteract effects of esmolol.
* Vasoconstrictive and positive inotropic agents:  Because of the risk of reducing cardiac contractility in presence of high systemic vascular resistance, do not use esmolol to control [[tachycardia]] in patients receiving drugs that are vasoconstrictive and have positive inotropic effects, such as [[epinephrine]], [[norepinephrine]], and [[dopamine]].
|FDAPregCat=C
|useInPregnancyFDA=* Esmolol hydrochloride has been shown to produce increased fetal resorptions with minimal maternal toxicity in rabbits when given in doses approximately 8 times the maximum human maintenance dose (300 mcg/kg/min). There are no adequate and well-controlled studies in pregnant women. BREVIBLOC injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

* [[Teratogenicity]] studies in rats at intravenous dosages of esmolol hydrochloride up to 3000 mcg/kg/min (10 times the maximum human maintenance dosage) for 30 minutes daily produced no evidence of maternal toxicity, embryotoxicity or [[teratogenicity]], while a dosage of 10,000 mcg/kg/min produced maternal toxicity and lethality. In rabbits, intravenous dosages up to 1000 mcg/kg/min for 30 minutes daily produced no evidence of maternal toxicity, embryotoxicity or [[teratogenicity]], while 2500 mcg/kg/min produced minimal maternal toxicity and increased fetal resorptions.
|useInPregnancyAUS=(Description)
|useInLaborDelivery=* Although there are no adequate and well-controlled studies in pregnant women, use of esmolol in the last trimester of pregnancy or during labor or delivery has been reported to cause fetal [[bradycardia]], which continued after termination of drug infusion. BREVIBLOC injection should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
|useInNursing=* It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from BREVIBLOC, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
|useInPed=* The safety and effectiveness of BREVIBLOC in pediatric patients have not been established.
|useInGeri=* Clinical studies of BREVIBLOC injection did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should usually start at the low end of the dosing range, reflecting greater frequency of decreased renal or cardiac function and of concomitant disease or other drug therapy.
|useInRenalImpair=* No dosage adjustment is required for esmolol in patients with renal impairment receiving a maintenance infusion of esmolol 150 mcg/kg for 4 hours. There is no information on the tolerability of maintenance infusions of esmolol using rates in excess of 150 mcg/kg or maintained longer than 4 hours.
|useInHepaticImpair=* No special precautions are necessary in patients with hepatic impairment because BREVIBLOC is metabolized by red-blood cell esterases.
|othersTitle=Others
|administration=Intravenous
|monitoring======Condition 1=====

(Description regarding monitoring, from ''Warnings'' section)

=====Condition 2=====

(Description regarding monitoring, from ''Warnings'' section)

=====Condition 3=====

(Description regarding monitoring, from ''Warnings'' section)
|IVCompat=Esmolol was tested for compatibility with ten commonly used intravenous fluids at a final concentration of 10 mg esmolol hydrochloride per mL. was found to be compatible with the following solutions and was stable for at least 24 hours at controlled room temperature or under refrigeration:

* [[Dextrose]] (5%) Injection, USP
* [[Dextrose]] (5%) in Lactated Ringer’s Injection
* [[Dextrose]] (5%) in Ringer’s Injection
* [[Dextrose]] (5%) and Sodium Chloride (0.45%) Injection, USP
* [[Dextrose]] (5%) and Sodium Chloride (0.9%) Injection, USP
* [[Lactated Ringer’s]] Injection, USP
* [[Potassium Chloride]] (40 mEq/liter) in [[Dextrose]] (5%) Injection, USP
* [[Sodium Chloride]] (0.45%) Injection, USP
* [[Sodium Chloride]] (0.9%) Injection, USP
|overdose====Acute Overdose===

====Signs and Symptoms====

(Description)

====Management====

(Description)

===Chronic Overdose===

====Signs and Symptoms====

(Description)

====Management====

(Description)
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|clinicalStudies======Condition 1=====

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|howSupplied=(Description)
|fdaPatientInfo=(Patient Counseling Information)
|alcohol=Alcohol-Esmolol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|lookAlike=* (Paired Confused Name 1a) — (Paired Confused Name 1b)
* (Paired Confused Name 2a) — (Paired Confused Name 2b)
* (Paired Confused Name 3a) — (Paired Confused Name 3b)
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