यह जानकारी केवल शैक्षणिक उद्देश्यों के लिए है। हमेशा किसी स्वास्थ्य सेवा पेशेवर से परामर्श लें। और जानें

Esmolol Hydrochloride

Prescription

ब्रांड नाम: Esmolol Hydrochloride

खुराक रूप
Injection
मार्ग
INTRAVENOUS
निर्माता
Gland Pharma Limited

About This Medication

11 DESCRIPTION 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 C 16 H 26 NO 4 Cl 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 Esmolol Hydrochloride Injection Dosage Forms Esmolol hydrochloride injection is a clear, colorless to light yellow, sterile, nonpyrogenic, iso-osmotic solution of esmolol hydrochloride in sodium chloride. The formulation is described in the table below: Table 4 Formulation for Esmolol Hydrochloride Injection Esmolol Hydrochloride, USP 10 mg/mL Sodium Chloride, USP 5.9 mg/mL Water for Injection, USP Q.S. to volume of 10 mL Sodium Acetate Trihydrate, USP 2.8 mg/mL Glacial Acetic Acid, USP 0.546 mg/mL Sodium Hydroxide Q.S. to adjust pH to 4.5 to 5.5 Hydrochloric Acid Q.S. to adjust pH to 4.5 to 5.5 Q.S. = Quantity sufficient esmolol-spl-structure

सक्रिय तत्व

घटक शक्ति
Esmolol Hydrochloride -

संकेत और उपयोग

1 INDICATIONS AND USAGE Esmolol hydrochloride injection is a beta adrenergic blocker indicated for the short-term treatment of: Control of ventricular rate in supraventricular tachycardia including atrial fibrillation and atrial flutter and control of heart rate in noncompensatory sinus tachycardia ( 1.1 ) Control of perioperative tachycardia and hypertension ( 1.2 ) 1.1 Supraventricular 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 injection is intended for short-term use. 1.2 Intraoperative and Postoperative Tachycardia and/or 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 injection to prevent such events is not recommended.

यह कैसे काम करता है

12.1 Mechanism of Action Esmolol hydrochloride injection is a beta 1 -selective (cardioselective) adrenergic receptor blocking agent with rapid onset, a very short duration of action, and no significant intrinsic sympathomimetic or membrane stabilizing activity at therapeutic dosages. Its elimination half-life after intravenous infusion is approximately 9 minutes. Esmolol hydrochloride injection inhibits the beta 1 receptors located chiefly in cardiac muscle, but this preferential effect is not absolute and at higher doses it begins to inhibit beta 2 receptors located chiefly in the bronchial and vascular musculature.

खुराक और प्रशासन

2 DOSAGE AND ADMINISTRATION • Administer intravenously ( 2.1 , 2.2 ) • Titrate using ventricular rate or blood pressure at ≥4-minute intervals. ( 2.1 , 2.2 ) • Supraventricular tachycardia (SVT) or noncompensatory sinus tachycardia ( 2.1 ) • Optional loading dose: 500 mcg per kg infused over one minute • Then 50 mcg per kg per minute for the next 4 minutes • Adjust dose as needed to a maximum of 200 mcg per kg per minute. • Additional loading doses may be administered • Perioperative tachycardia and hypertension ( 2.2 ) • Loading dose: 500 mcg per kg over 1 minute for gradual control (1 mg per kg over 30 seconds for immediate control) • Then 50 mcg per kg per min for gradual control (150 mcg per kg per minute for immediate control) adjusted to a maximum of 200 (tachycardia) or 300 (hypertension) mcg per kg per min ( 2.2 ) 2.1 Dosing for the Treatment of Supraventricular Tachycardia or Noncompensatory Sinus Tachycardia Esmolol hydrochloride 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. Table 1 Step-Wise Dosing Step Action 1 Optional loading dose (500 mcg per kg over 1 minute),then 50 mcg per kg per min for 4 min 2 Optional loading dose if necessary, then 100 mcg per kg per min for 4 min 3 Optional loading dose if necessary, then 150 mcg per kg per min for 4 min 4 If necessary, increase dose to 200 mcg per kg per min 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 to 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 Esmolol Hydrochloride 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 hydrochloride injection to alternative drugs, the physician should carefully consider the labeling instructions of the alternative drug selected and reduce the dosage of esmolol hydrochloride injection as follows: Thirty minutes following the first dose of the alternative drug, reduce the esmolol hydrochloride 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 hydrochloride infusion. 2.4 Directions for Use Esmolol hydrochloride injection is available in a ready-to-use vial. Esmolol hydrochloride injection 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. 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 [see How Supplied/Storage and Handling ( 16.2 )]. Compatibility with Commonly Used Intravenous Fluids Esmolol hydrochloride injection was tested for compatibility with ten commonly used intravenous fluids at a final concentration of 10 mg esmolol hydrochloride per mL. Esmolol hydrochloride injection 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

Side Effects Overview

6 ADVERSE REACTIONS Most common adverse reactions (incidence >10%) are symptomatic hypotension (hyperhidrosis, dizziness) and asymptomatic hypotension ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma at 864-879-9994 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 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 ( 5.1 )]. Deaths have been reported in post-marketing experience occurring during complex clinical states where esmolol hydrochloride injection was presumably being used simply to control ventricular rate [see Warnings and Precautions ( 5.5 )] . Table 3 Clinical Trial Adverse Reactions (Frequency ≥3%) System Organ Class (SOC) Preferred MedDRA Term Frequency VASCULAR DISORDERS Hypotension* Asymptomatic hypotension Symptomatic hypotension (hyperhidrosis, dizziness) 25% 12% GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS Infusion site reactions (inflammation and induration) 8% GASTROINTESTINAL DISORDERS Nausea 7% NERVOUS SYSTEM DISORDERS Dizziness 3% Somnolence 3% * Hypotension resolved during esmolol hydrochloride infusion in 63% of patients. In 80% of the remaining patients, hypotension resolved within 30 minutes following discontinuation of infusion. 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

चेतावनियाँ और सावधानियाँ

प्रतिनिर्देश

फार्माकोकाइनेटिक्स

12.3 Pharmacokinetics Esmolol is rapidly metabolized by hydrolysis of the ester linkage, chiefly by the esterases in the cytosol of red blood cells and not by plasma cholinesterases or red cell membrane acetylcholinesterase. Total body clearance in man was found to be about 20 L/kg/hr, which is greater than cardiac output; thus the metabolism of esmolol is not limited by the rate of blood flow to metabolizing tissues such as the liver or affected by hepatic or renal blood flow. Esmolol has a rapid distribution half-life of about 2 minutes and an elimination half-life of about 9 minutes. Using an appropriate loading dose, steady-state blood levels of esmolol hydrochloride injection for dosages from 50 to 300 mcg/kg/min are obtained within five minutes. Steady-state is reached in about 30 minutes without the loading dose. Steady-state blood levels of esmolol increase linearly over this dosage range and elimination kinetics are dose-independent over this range. Steady-state blood levels are maintained during infusion but decrease rapidly after termination of the infusion. Because of its short half-life, blood levels of esmolol can be rapidly altered by increasing or decreasing the infusion rate and rapidly eliminated by discontinuing the infusion. Consistent with the high rate of blood-based metabolism of esmolol, less than 2% of the drug is excreted unchanged in the urine. Within 24 hours of the end of infusion, the acid metabolite of esmolol in urine accounts for approximately 73 to 88% of the dosage. Metabolism of esmolol results in the formation of the corresponding free acid and methanol. The acid metabolite has been shown in animals to have negligible activity and in normal volunteers its blood levels do not correspond to the level of beta blockade. The acid metabolite has an elimination half-life of about 3.7 hours and is excreted in the urine with a clearance approximately equivalent to the glomerular filtration rate. After a 4 hour maintenance infusion of 150 mcg/kg, the plasma concentrations of esmolol are similar in subjects with normal renal function and in patients with ESRD on dialysis. The half-life of the acid metabolite of esmolol hydrochloride injection, which is primarily excreted unchanged by the kidney, is increased about 12-fold to 48 hours in patients with ESRD. The peak concentrations of the acid metabolite are doubled in ESRD. Methanol blood levels, monitored in subjects receiving esmolol hydrochloride injection for up to 6 hours at 300 mcg/kg/min and 24 hours at 150 mcg/kg/min, approximated endogenous levels and were less than 2% of levels usually associated with methanol toxicity. Esmolol hydrochloride injection has been shown to be 55% bound to human plasma protein, while the acid metabolite is only 10% bound.

Frequently Asked Questions

1 INDICATIONS AND USAGE Esmolol hydrochloride injection is a beta adrenergic blocker indicated for the short-term treatment of: Control of ventricular rate in supraventricular tachycardia including atrial fibrillation and atrial flutter and control of heart rate in noncompensatory sinus tachycardia ( 1.1 ) Control of perioperative tachycardia and hypertension ( 1.2 ) 1.1 Supraventricular 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 …

2 DOSAGE AND ADMINISTRATION • Administer intravenously ( 2.1 , 2.2 ) • Titrate using ventricular rate or blood pressure at ≥4-minute intervals. ( 2.1 , 2.2 ) • Supraventricular tachycardia (SVT) or noncompensatory sinus tachycardia ( 2.1 ) • Optional loading dose: 500 mcg per kg infused over one minute • Then 50 mcg per kg per minute for the next 4 minutes • Adjust dose as needed to a maximum of 200 mcg per kg per minute. • …

5 WARNINGS AND PRECAUTIONS • Risk of hypotension, bradycardia, and cardiac failure: Monitor for signs and symptoms of cardiovascular adverse effects. Reduce or discontinue use ( 5.1 , 5.2 , 5.3 , 5.10 ) • Risk of exacerbating reactive airway disease ( 5.5 ) • Diabetes: May mask symptoms of hypoglycemia and alter glucose levels; monitor ( 5.6 ) • Risk of unopposed alpha-agonism and severe hypertension in untreated pheochromocytoma ( 5.9 ) • Risk of myocardial ischemia when abruptly …

4 CONTRAINDICATIONS 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 ( 5.2 )]. 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 …

Esmolol Hydrochloride is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

Similar Injection Products

Browse all Injection products →

References & Data Sources

चिकित्सा अस्वीकरण

इस पृष्ठ पर दी गई जानकारी केवल शैक्षणिक उद्देश्यों के लिए है और इसे पेशेवर चिकित्सा सलाह, निदान या उपचार के विकल्प के रूप में उपयोग नहीं किया जाना चाहिए।

किसी चिकित्सा स्थिति या दवा के बारे में आपके किसी भी प्रश्न के लिए हमेशा अपने चिकित्सक या अन्य योग्य स्वास्थ्य सेवा प्रदाता की सलाह लें।

डेटा स्रोत: DailyMed (NLM), openFDA, MFDS

Medical Disclaimer

This content is for educational and informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before making medication decisions.

Data sources: ChEMBL, PubChem, DailyMed.