Esmolol

C07A - Beta blocking agents ATC C07AB09 Small molecule approved 1986 Parenteral Natural product Withdrawn

JFDA label: Esobloc 100mg/10ml

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

Indications

Approved

Intraoperative and postoperative tachycardia and/or hypertension
Noncompensatory sinus tachycardia
Supraventricular tachycardia (SVT)

Off-label

Acute coronary syndromes (arrhythmia/rate control)
Cardiogenic shock
Electroconvulsive therapy (attenuation of adrenergic response)
Hypertensive emergencies
Intubation (attenuation of adrenergic response)
Thyroid storm or thyrotoxicosis
Thyrotoxicosis

Contraindications

Source: Lexicomp

Additional contraindications (not in US labeling): Patients requiring inotropic agents and/or vasopressors to maintain cardiac output and systolic blood pressure Absolute
Hypersensitivity to esmolol or any component of the formulation Absolute
IV administration of calcium channel blockers (eg, verapamil) in close proximity to esmolol (ie, while effects of other drug are still present) Absolute
cardiogenic shock Absolute
decompensated heart failure Absolute
heart block greater than first degree (except in patients with a functioning artificial ventricular pacemaker) Absolute
hypotension Absolute
pulmonary hypertension Absolute
right ventricular failure secondary to pulmonary hypertension Absolute
severe sinus bradycardia Absolute
sick sinus syndrome Absolute
untreated pheochromocytoma Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Common Peripheral ischemia

Nervous system disorders (5)

Common agitation · confusion · Dizziness · drowsiness · headache

Gastrointestinal disorders (2)

Common Nausea · vomiting

General disorders and administration site conditions (1)

Common Infusion site reaction

Other (3)

Very Common asymptomatic hypotension · Cardiovascular: Decreased blood pressure · symptomatic hypotension

Dosing

Source: Lexicomp

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 (SVT) 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. Acute coronary syndromes (when relative contraindications to beta-blockade exist; off-label use): IV: 500 mcg/kg over 1 minute; follow with a 50 mcg/kg/minute i

Refer to adult dosing.

No dosage adjustment necessary. Not removed by hemo- or peritoneal dialysis. Supplemental dose is not necessary.

No dosage adjustment necessary.

Warnings & Precautions

Source: Lexicomp

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's disease

Can precipitate or aggravate symptoms of arterial insufficiency in patients with PVD and Raynaud's 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:

Calcium channel blockers

Use with caution in patients on concurrent verapamil or diltiazem; bradycardia or heart block can occur (may be fatal). Use is contraindicated when IV calcium channel blockers have been administered in close proximity to esmolol (ie, while effects of other drug are still present).

Cardiac glycosides

Use with caution in patients receiving digoxin; bradycardia or heart block can occur. 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.

Pregnancy & Lactation

Pregnancy

FDA category C

Adverse events were observed in some animal reproduction studies. Esmolol has been shown to cause fetal bradycardia. Adverse fetal/neonatal events have also been observed with the chronic use of beta-blockers during pregnancy; however, esmolol is a short-acting beta-blocker and not indicated for chronic use. Esmolol is approved for the treatment of supraventricular tachycardia (SVT); however, other agents are preferred in pregnant women (ACC/AHA/HRS [Page 2015]).

Lactation

It is not known if esmolol is present in breast milk. Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother. The short half-life and the fact that it is not intended for chronic use should limit any potential exposure to the breastfeeding infant.

Monitoring

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

Chemistry & Properties

Formula	C16H25NO4
Molecular weight	295.38 g/mol
IUPAC name	methyl 3-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]propanoate
CAS	81147-92-4
PubChem CID	59768
InChIKey	`AQNDDEOPVVGCPG-UHFFFAOYSA-N`
logP	1.53 (XLogP 1.9)
Polar surface area	67.79 Å²
H-bond acceptors / donors	5 / 2
Drug-likeness (QED)	0.68
Lipinski violations	0

SMILES

COC(=O)CCc1ccc(OCC(O)CNC(C)C)cc1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	1.294 h
Volume of distribution	1.349 L/kg
Protein binding	44.7%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Substrate	—
CYP2C19	Substrate	—
CYP2D6	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Aminophylline	major
Ceritinib	major
Dolasetron	major
Dyphylline	major
Fingolimod	major
Methacholine	major
Oxtriphylline	major
Siponimod	major
Theophylline	major
Acetohexamide	moderate
Aldesleukin	moderate
Alectinib	moderate
Alimemazine	moderate
Amifostine	moderate
Brigatinib	moderate
Brimonidine (ophthalmic)	moderate
Brimonidine (topical)	moderate
Bupropion	moderate
Canagliflozin	moderate
Chlorphenesin	moderate
Chlorpropamide	moderate
Cimetidine	moderate
Codeine	moderate
Crizotinib	moderate
Dapagliflozin	moderate
Diatrizoate	moderate
Diclofenac	moderate
Diphenhydramine	moderate
Doxepin	moderate
Doxepin (topical)	moderate
Dronabinol	moderate
Empagliflozin	moderate
Ephedrine	moderate
Epinephrine	moderate
Epoprostenol	moderate
Ertugliflozin	moderate
Ethanol	moderate
Flurbiprofen	moderate
Formoterol	moderate
Gadobenic acid	moderate

Showing 40 of 100+.

Registered Products (2)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Esobloc	Vial 100 mg/10 ml	1 vial	Hikma Pharmaceuticals Co.Ltd/Jordan	—
Pol-esmolol	Infusion 10 mg/ml	250 ml	JAWEDA INT. DRUD STORE	—