FDA

Esmolol Hydrochloride

Approved 2 May 2005InjectionInjectable

The FDA lists this product in 17 strengths and forms.

Indications

1.1Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

Esmolol hydrochloride injection is indicated for the rapid control of ventricular rate in patients with atrial fibrillation or atrial flutter in perioperative, postoperative, or other emergent circumstances where short-term control of ventricular rate with a short-acting agent is desirable. Esmolol hydrochloride injection is also indicated in noncompensatory sinus tachycardia where, in the physician’s judgment, the rapid heart rate requires specific intervention.

Esmolol hydrochloride is intended for short-term use.

1.2Intraoperative and Postoperative Tachycardia and Hypertension

Esmolol hydrochloride injection is indicated for the short-term treatment of tachycardia and hypertension that occur during induction and tracheal intubation, during surgery, on emergence from anesthesia and in the postoperative period, when in the physician’s judgment such specific intervention is considered indicated. Use of esmolol hydrochloride to prevent such events is not recommended.

Contraindications

Esmolol hydrochloride is contraindicated in patients with: Severe sinus bradycardia: May precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest [see WARNINGS AND PRECAUTIONS (5.2)]. Heart block greater than first degree: Second- or third-degree atrioventricular block may precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest [see WARNINGS AND PRECAUTIONS (5.2)].

Sick sinus syndrome: May precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest [see WARNINGS AND PRECAUTIONS (5.2)]. Decompensated heart failure: May worsen heart failure. Cardiogenic shock: May precipitate further cardiovascular collapse and cause cardiac arrest. IV administration of cardiodepressant calcium-channel antagonists (e.g.,verapamil) and esmolol hydrochloride in close proximity (i.e., while cardiac effects from the other are still present); fatal cardiac arrests have occurred in patients receiving esmolol hydrochloride 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).

At a glance

Brand name: Esmolol Hydrochloride
Route: Injection
Dosage form: Injectable
Applicant: Fresenius Kabi USA
Status: Discontinued
FDA approval: 2 May 2005
Application: ANDA076573-002

Indications

1.1Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

Esmolol hydrochloride is intended for short-term use.

1.2Intraoperative and Postoperative Tachycardia and Hypertension

Contraindications

Interactions

Concomitant use of esmolol hydrochloride 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 hydrochloride’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. (See clonidine, guanfacine, and moxonidine below.) Esmolol hydrochloride 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 hydrochloride leads to an approximate 10% to 20% increase of digoxin blood levels at some time points.

Digoxin does not affect esmolol hydrochloride pharmacokinetics. Both digoxin and beta blockers slow atrioventricular conduction and decrease heart rate. Concomitant use increases the risk of bradycardia. Anticholinesterases: Esmolol hydrochloride 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 clondidine-, 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 infarction, use of esmolol hydrochloride 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 hydrochloride.

Vasoconstrictive and positive inotropic agents: Because of the risk of reducing cardiac contractility in presence of high systemic vascular resistance, do not use esmolol hydrochloride to control tachycardia in patients receiving drugs that are vasoconstrictive and have positive inotropic effects, such as epinephrine, norepinephrine, and dopamine.

Adverse reactions

6.1Clinical 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 hydrochloride 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 [see WARNINGS AND PRECAUTIONS (5.3)]. Deaths have been reported in post-marketing experience occurring during complex clinical states where esmolol hydrochloride was presumably being used simply to control ventricular rate [see WARNINGS AND PRECAUTIONS (5.5)].

Table 3: Clinical Trial Adverse Reactions (Frequency ≥3%) Clinical Trial Adverse Reactions (Frequency <3%) Psychiatric Disorders Confusional 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 have (<1%) Renal and Urinary Disorders Urinary retention (<1%)

6.2Post-Marketing Experience

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 ADVERSE

Esmolol Hydrochloride

Indications

1.1Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

1.2Intraoperative and Postoperative Tachycardia and Hypertension

Contraindications

At a glance

Two medicines in one question?

Esmolol Hydrochloride

Indications

1.1Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia

1.2Intraoperative and Postoperative Tachycardia and Hypertension

Contraindications

At a glance

Two medicines in one question?

Warnings and precautions

5.1Hypotension

5.2Bradycardia

5.3Cardiac Failure

5.4Intraoperative and Postoperative Tachycardia and Hypertension

5.5Reactive Airways Disease Patients

5.6Use in Patients with Diabetes Mellitus and Hypoglycemia

5.7Infusion Site Reactions

5.8Use in Patients with Prinzmetal's Angina

5.9Use in Patients with Pheochromocytoma

5.10Use in Hypovolemic Patients

5.11Use in Patients with Peripheral Circulatory Disorders

5.12Abrupt Discontinuation of Esmolol Hydrochloride

5.13Hyperkalemia

5.14Use in Patients with Metabolic Acidosis

5.15Use in Patients with Hyperthyroidism

5.16Use in Patients at Risk of Severe Acute Hypersensitivity Reactions

Interactions

Adverse reactions

6.1Clinical Trials Experience

6.2Post-Marketing Experience

Composition

Strengths and forms

Official product information