Brevicard (Solution) Instructions for Use

ATC Code

C07AB09 (Esmolol)

Active Substance

Esmolol (Rec.INN)

Clinical-Pharmacological Group

Beta₁-adrenoblocker

Pharmacotherapeutic Group

Beta-adrenergic blockers; selective beta-adrenergic blockers

Pharmacological Action

Cardioselective beta-adrenoblocker without intrinsic sympathomimetic and membrane-stabilizing activity. It has antianginal, antihypertensive, and antiarrhythmic effects. The antihypertensive effect is due to a reduction in catecholamine-stimulated cAMP formation from ATP, intracellular calcium current, a decrease in heart rate, and a reduction in myocardial contractility.

The antianginal effect is due to a reduction in myocardial oxygen demand as a result of a decrease in heart rate (prolongation of diastole and improvement of myocardial perfusion) and a reduction in contractility.

Due to an increase in left ventricular end-diastolic pressure and increased stretching of ventricular muscle fibers, it may increase oxygen demand, especially in patients with chronic heart failure.

The antiarrhythmic effect is determined by the inhibition of impulse conduction in the antegrade and, to a lesser extent, retrograde directions through the AV node and via accessory pathways.

The action begins upon administration, the full therapeutic effect develops 2 minutes after administration and ends 10-20 minutes after the infusion is stopped.

Pharmacokinetics

Plasma protein binding after IV administration is 55%. C_ss in blood is achieved within 5 minutes when using a loading dose and after 30 minutes without it. It is rapidly hydrolyzed by esterases in erythrocytes to a free acid metabolite (its activity is 1/1500 of the activity of esmolol) and methanol. T_1/2 is 9 minutes, for the free acid metabolite it is 3.7 hours (increases 10-fold in chronic renal failure). It is excreted by the kidneys as a metabolite.

Indications

Sinus and supraventricular tachycardia, supraventricular tachyarrhythmia (atrial fibrillation, atrial flutter), arterial hypertension, including during and after surgery.

ICD codes

Dosage Regimen

Solution

IV, IV drip. The dose is set by administering a series of loading and maintenance doses. For arrhythmias – initially, using a dosing device, a loading dose of 500 mcg/kg is administered over 1 minute, then at a rate of 50 mcg/kg/min for the next 4 minutes; upon achieving the desired effect – a maintenance dose of 25 mcg/kg/min. Breaks of 5 to 10 minutes between repeated administration are possible. If the effect is insufficient by the end of 5 minutes, the loading dose should be repeated, then 100 mcg/kg/min should be administered over 4 minutes (with repeated attempts, this dose can be increased to 150 and then 200 mcg/kg/min).

During surgical anesthesia – IV bolus, 80 mcg over 15-30 seconds, then infusion at a rate of 150-300 mcg/min. Arterial hypertension or arrhythmia during or after surgery – IV, 250-500 mcg/kg over 1 minute (loading dose), then IV drip over 4 minutes – 50 mcg/kg/min (maintenance dose). If there is no effect, it is administered repeatedly, up to 4 times (loading and maintenance dose, increasing each subsequent maintenance dose by 50 mcg/kg). The maximum maintenance dose for adults is 200 mcg/kg/min. For children with supraventricular arrhythmia – IV drip, 50 mcg/kg/min with a subsequent increase in dose (if necessary) every 10 minutes up to 300 mcg/kg/min.

Adverse Reactions

From the cardiovascular system pronounced decrease in BP (symptomatic – 12%, asymptomatic – 25%), 1% – peripheral circulation disorders; less than 1% – pulmonary edema, bradycardia, palpitations, AV block, ventricular asystole, syncope, collapse, thrombophlebitis, facial flushing.

From the CNS and peripheral nervous system: 3% – drowsiness, anxiety; 2% – headache, agitation, confusion, feeling of fatigue; less than 1% – dizziness, paresthesia, asthenia, depression, convulsions, thinking impairment, taste, vision, speech impairment.

From the digestive system: 7% – nausea; 1% – vomiting; less than 1% – dry mouth, dyspepsia, decreased appetite, abdominal pain, constipation.

From the respiratory system: less than 1% – nasal congestion, chest pain and wheezing, difficulty breathing, bronchospasm, shortness of breath.

From the urinary system: less than 1% – edema, urination disorder.

From the skin: 8% – skin hyperemia; less than 1% – pallor or discoloration of the skin, acrocyanosis, erythematous rash, skin necrosis (in case of accidental extravasal administration).

Other: swelling at the injection site, hyperthermia, increased sweating, chills, pain in the interscapular region, cold hands and feet, withdrawal syndrome.

Contraindications

Bradycardia (heart rate less than 45/min), AV block II-III degree, arterial hypotension (systolic BP below 90 mm Hg, diastolic BP below 50 mm Hg), cardiogenic shock, acute heart failure, sick sinus syndrome, sinoatrial block, bleeding, hypovolemia, lactation period, hypersensitivity to esmolol.

Use in Pregnancy and Lactation

Use with caution during pregnancy.

In experimental studies, when administered in doses exceeding the maximum maintenance dose for humans by 8 times (rabbits) and 30 times (rats), it has a toxic effect on the maternal body, increases the frequency of resorption and fetal mortality.

Contraindicated during lactation.

Use in Renal Impairment

Should be used with caution in chronic renal failure.

Pediatric Use

Experience of use in children is limited.

Geriatric Use

Should be used with caution in the elderly.

Special Precautions

Should be used with caution in bronchial asthma, COPD (emphysema, chronic obstructive bronchitis), chronic heart failure, chronic renal failure, in secondary hypertension (due to vasoconstriction, during or after surgery, against the background of hypothermia), diabetes mellitus, pregnancy, elderly age.

During treatment, careful and constant monitoring of ECG, BP, and heart rate is necessary. The use of butterfly needles for administration is not recommended.

Experience of use in children is limited.

It is necessary to consider the possibility of masking the signs of hypoglycemia (tachycardia, increased BP) in patients with diabetes mellitus.

Against the background of a burdened allergic history, a more severe manifestation of allergic reactions and the absence of a therapeutic effect from usual doses of epinephrine are possible.

At concentrations exceeding 10 mg/ml, tissue irritation is possible; if a local reaction occurs during infusion, the administration must be stopped and the injection site changed.

Drug Interactions

Incompatible in the same syringe with other medicinal products (including with 5% sodium bicarbonate solution).

Increases the plasma concentration of digoxin.

Morphine, suxamethonium, and indirect anticoagulants increase the concentration of esmolol in the blood. Increases the duration of neuromuscular blockade caused by suxamethonium by 1.5 times.

Allergens used for immunotherapy or allergen extracts for skin tests increase the risk of severe systemic allergic reactions or anaphylaxis in patients receiving Esmolol.

Iodine-containing X-ray contrast medicinal products for IV administration increase the risk of anaphylactic reactions.

Phenytoin with IV administration, medicinal products for inhalation anesthesia (hydrocarbon derivatives) increase the severity of the cardiodepressive effect and the likelihood of decreased BP.

Alters the effectiveness of insulin and oral hypoglycemic agents, masks the symptoms of developing hypoglycemia (tachycardia, increased BP).

Reduces the clearance of lidocaine and xanthines (except diphylline) and increases their plasma concentration, especially in patients with initially increased theophylline clearance due to smoking.

The antihypertensive effect is weakened by NSAIDs (sodium retention and blockade of prostaglandin synthesis in the kidneys), corticosteroids and estrogens (sodium retention).

Cardiac glycosides, methyldopa, reserpine and guanfacine, calcium channel blockers (verapamil, diltiazem), amiodarone and other antiarrhythmic agents increase the risk of development or worsening of bradycardia, AV block, cardiac arrest and heart failure.

Nifedipine can lead to a significant decrease in BP.

With simultaneous use with antihypertensive agents (including diuretics, clonidine, sympatholytics, hydralazine), excessive BP reduction is possible.

Prolongs the action of non-depolarizing muscle relaxants and the anticoagulant effect of coumarins.

Tricyclic and tetracyclic antidepressants, antipsychotic agents (neuroleptics), ethanol, sedatives and hypnotics enhance CNS depression.

Simultaneous use with MAO inhibitors is not recommended due to a significant enhancement of the hypotensive effect; the break in treatment between taking MAO inhibitors and esmolol should be at least 14 days.

Non-hydrogenated ergot alkaloids increase the risk of peripheral circulation disorders.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.