Esmolol Hydrochloride
FDA Drug Information • Also known as: Brevibloc, Esmolol Hydrochloride, Esmolol Hydrochloride In Water
- Brand Names
- Brevibloc, Esmolol Hydrochloride, Esmolol Hydrochloride In Water
- Dosage Form
- POWDER
- Product Type
- BULK INGREDIENT
Description
11 DESCRIPTION BREVIBLOC (Esmolol Hydrochloride) injection is a beta adrenergic receptor blocker with a very short duration of action (elimination half-life is approximately 9 minutes). Esmolol hydrochloride is:
(±)-Methyl p-[2-hydroxy-3-(isopropylamino) propoxy] hydrocinnamate hydrochloride and has the following structure: Esmolol hydrochloride has the empirical formula C16H26NO4Cl and a molecular weight of 331.8. It has one asymmetric center and exists as an enantiomeric pair. Esmolol hydrochloride is a white to off-white crystalline powder. It is a relatively hydrophilic compound which is very soluble in water and freely soluble in alcohol. Its partition coefficient (octanol/water) at pH 7.0 is 0.42 compared to 17.0 for propranolol. 11.1 BREVIBLOC Injection Dosage Forms All BREVIBLOC injection presentations are clear, colorless to light yellow, sterile, nonpyrogenic, iso-osmotic solutions of esmolol hydrochloride in sodium chloride. The formulations for BREVIBLOC PREMIXED Injection, BREVIBLOC PREMIXED Double Strength Injection, and BREVIBLOC Injection are described in the table below: The calculated osmolarity of BREVIBLOC PREMIXED Injection and BREVIBLOC PREMIXED Double Strength Injection is 312 mOsmol/L. The 250 mL and 100 mL bags are non-latex, non-PVC INTRAVIA bags with dual PVC ports. The INTRAVIA bags are manufactured from a specially designed multilayer plastic (PL 2408). Solutions in contact with the plastic container leach out certain chemical compounds from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials. STRUCTURE DESCRIPTIONWhat Is Esmolol Hydrochloride Used For?
1 INDICATIONS & USAGE 1.1 Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia BREVIBLOC (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. BREVIBLOC injection is also indicated in noncompensatory sinus tachycardia where, in the physician’s judgment, the rapid heart rate requires specific intervention. BREVIBLOC injection is intended for short-term use. 1.2 Intraoperative and Postoperative Tachycardia and/or Hypertension BREVIBLOC (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 BREVIBLOC injection to prevent such events is not recommended.
Dosage and Administration
2 DOSAGE & ADMINISTRATION 2.1 Dosing for the Treatment of Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia BREVIBLOC injection 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. 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. 2.2 Intraoperative and Postoperative Tachycardia and Hypertension 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. 2.3 Transition from BREVIBLOC 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 BREVIBLOC injection to alternative drugs, the physician should carefully consider the labeling instructions of the alternative drug selected and reduce the dosage of BREVIBLOC injection as follows: 1. Thirty minutes following the first dose of the alternative drug, reduce the BREVIBLOC infusion rate by one-half (50%). 2. 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 BREVIBLOC infusion. 2.4 Directions for Use BREVIBLOC...Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS 6.1 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 BREVIBLOC (Esmolol Hydrochloride) injection 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- 5.1)]. Deaths have been reported in post-marketing experience occurring during complex clinical states where BREVIBLOC injection was presumably being used simply to control ventricular rate [see Warnings and Precautions ( 5- 5.5)]. 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 (<1%) Renal and Urinary Disorders Urinary retention (<1%) 6.2 Post-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
Drug Interactions
7 DRUG INTERACTIONS Concomitant use of BREVIBLOC 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 BREVIBLOC injection’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.) BREVIBLOC injection 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 BREVIBLOC injection leads to an approximate 10% to 20% increase of digoxin blood levels at some time points. Digoxin does not affect BREVIBLOC injection pharmacokinetics. Both digoxin and beta blockers slow atrioventricular conduction and decrease heart rate. Concomitant use increases the risk of bradycardia. Anticholinesterases: BREVIBLOC injection 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 BREVIBLOC injection 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 BREVIBLOC injection. Vasoconstrictive and positive inotropic agents: Because of the risk of reducing cardiac contractility in presence of high systemic vascular resistance, do not use BREVIBLOC injection to control tachycardia in patients receiving drugs that are vasoconstrictive and have positive inotropic effects, such as epinephrine, norepinephrine, and dopamine.Contraindications
4 CONTRAINDICATIONS BREVIBLOC (Esmolol Hydrochloride) injection 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- 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- 5.2)]. Sick sinus syndrome: May precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest [see Warnings and Precautions ( 5- 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 BREVIBLOC injection in close proximity (i.e., while cardiac effects from the other are still present); fatal cardiac arrests have occurred in patients receiving BREVIBLOC injection 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).Overdosage
10 OVERDOSAGE 10.1 Signs and Symptoms of Overdose Overdoses of BREVIBLOC (Esmolol Hydrochloride) injection can cause cardiac and central nervous system effects. These effects may precipitate severe signs, symptoms, sequelae, and complications (for example, severe cardiac and respiratory failure, including shock and coma), and may be fatal. Continuous monitoring of the patient is required.
Cardiac effects include bradycardia, atrioventricular block (1st -, 2nd -, 3rd degree), junctional rhythms, intraventricular conduction delays, decreased cardiac contractility, hypotension, cardiac failure (including cardiogenic shock), cardiac arrest/asystole, and pulseless electrical activity. Central nervous system effects include respiratory depression, seizures, sleep and mood disturbances, fatigue, lethargy, and coma. In addition, bronchospasm, mesenteric ischemia, peripheral cyanosis, hyperkalemia, and hypoglycemia (especially in children) may occur. 10.2 Treatment Recommendations Because of its approximately 9-minute elimination half-life, the first step in the management of toxicity should be to discontinue the BREVIBLOC infusion. Then, based on the observed clinical effects, consider the following general measures. Bradycardia Consider intravenous administration of atropine or another anticholinergic drug or cardiac pacing. Cardiac Failure Consider intravenous administration of a diuretic or digitalis glycoside. In shock resulting from inadequate cardiac contractility, consider intravenous administration of dopamine, dobutamine, isoproterenol, or inamrinone. Glucagon has been reported to be useful. Symptomatic hypotension Consider intravenous administration of fluids or vasopressor agents such as dopamine or norepinephrine. Bronchospasm Consider intravenous administration of a beta2 stimulating agent or a theophylline derivative. 10.3 Dilution Errors Massive accidental overdoses of BREVIBLOC injection have resulted from dilution errors. Use of BREVIBLOC PREMIXED...How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING BREVIBLOC PREMIXED INJECTION ESMOLOL HYDROCHLORIDE IN SODIUM CHLORIDE is supplied in the following dosage forms. NDC 51662-1427-1 BREVIBLOC PREMIXED INJECTION ESMOLOL HYDROCHLORIDE IN SODIUM CHLORIDE 2,500mg/250mL (10mg/mL) 250mL BAG HF Acquisition Co LLC, DBA HealthFirst Mukilteo, WA 98275 Also supplied in the following manufacture supplied dosage forms 16.1 How Supplied BREVIBLOC PREMIXED Injection
NDC 10019-055-61, 2500 mg / 250 mL (10 mg/mL) Ready-to-use INTRAVIA Bags BREVIBLOC PREMIXED Double Strength Injection NDC 10019-075-87, 2000 mg / 100 mL (20 mg/mL) Ready-to-use INTRAVIA Bags BREVIBLOC Injection NDC 10019-115-01, 100 mg / 10 mL (10 mg/mL) Ready-to-use Vials, Package of 25 16.2 Storage Store at 25˚C (77˚F). Excursions permitted to 15˚-30˚C (59˚-86˚F) [see USP Controlled Room Temperature]. Protect from freezing. Avoid excessive heat. Each bag contains no preservative. Once drug has been withdrawn from ready-to-use bag, the bag should be used within 24 hours, with any unused portion discarded. Visually inspect the container. If the administration port protector is damaged, detached, or not present, discard container as solution path sterility may be impaired. Do not use plastic containers in series connections. Such use could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed. Do not remove unit from overwrap until ready to use. Do not use if overwrap has been previously opened or damaged. The overwrap is a moisture barrier. The inner bag maintains sterility of the solution. Tear overwrap at notch and remove premixed bag. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually. Check for minute leaks by squeezing the inner bag firmly. If leaks are found,...About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.