Brevyblok - instructions for use, doses, side effects, contraindications

Active substanceEsmololEsmolol

Similar drugsTo uncover

Breviblock

solution d / infusion

Baxter Helskea Limited United Kingdom

Breviblock

solution in / in

Baxter Helskea Limited United Kingdom

Dosage form: & nbspsolution for infusions

Composition:

In 1 ml of the drug contains:

active substance: esmolol hydrochloride 10.0 mg;

Excipients: sodium chloride 5.9 mg, sodium acetate trihydrate 2.8 mg, glacial acid 0.546 mg, hydrochloric acid to pH 5.0, sodium hydroxide to pH 5.0, water for injection up to 1 ml.

Description:

Transparent solution from colorless to light yellow color.

Pharmacotherapeutic group:Beta1-blocker selective

ATX: & nbsp

C.07.A.B Selective beta-blockers

C.07.A.09 Esmolol

Pharmacodynamics:

Pharmacodynamics

Esmolol is a cardioselective blocker of β-adrenergic receptors, which has a rapid onset of action and a very short duration of action, whereby the dose can be rapidly changed. In therapeutic doses does not have a significant internal sympathomimetic and membrane-stabilizing activity; has antianginal, antihypertensive and antiarrhythmic effect.

Reduces catecholamine-stimulated formation of cyclic adenosine monophosphate from adenosine triphosphate,reduces the intracellular current of calcium ions, reduces the heart rate (HR), blocks the increase in heart rate by isoprenaline, increases the recovery time of the sinoatrial node of the Kis-Flak, slows AV (atrioventricular) conduction, increases the AV interval at a normal sinus rhythm and during atrial stimulation without retardation in the bundle of the Hisnia and fibers Purkinje, increases PQ (inter-peak) interval, induces AV blockade of the II degree, increases the functional refractory period of the atria and ventricles, t negative inotropic effect with a decrease in the ejection fraction and a negative butmotropic effect, reduces blood pressure.

When using an adequate loading dose, the equilibrium state in the blood is reached within 5 minutes. However, the therapeutic effect is achieved earlier than a stable concentration in the blood plasma. To obtain the desired pharmacological effect, one can use the regulation of the infusion rate.

Antiarrhythmic effect is determined by inhibition of impulses in anterograde and, to a lesser extent, in retrograde directions through the atrioventricular node and along additional paths.

The action begins from the moment of administration, the full therapeutic effect develops 2 minutes after the administration and ends 10-20 minutes after the infusion has stopped.

Esmolol, by its chemical nature, belongs to the class of phenoxypropanolamine beta-adrenoblockers. It has an enzymatically labile ester link, which is rapidly metabolized and has a short half-life from the blood plasma.

In patients older than 65 years, there was no difference in hemodynamic effects compared with younger patients.

Pharmacokinetics:

The kinetics of esmolol is linear in healthy adult volunteers, the concentration in the blood plasma is proportional to the dose. If the loading dose is not applied, the equilibrium concentration in the blood is reached within 30 minutes at doses of 50 to 300 μg / kg per minute. The half-life of esmolol hydrochloride is very short - about 2 minutes. The volume of distribution is 3.4 l / kg.

Esmolol is metabolized by erythrocyte esterases to methanol (by hydrolysis of the esterol ester group) and acid metabolite ASL-8123, which has a weak (less than 0.1% of esmolol) beta-adrenergic blocking activity. At doses of 50 to 300 μg / kg / min, the metabolism of esmolol hydrochloride is independent. Esmolol hydrochloride by 55% is associated with plasma proteins (for the acid metabolite, this figure is only 10%). The half-life of esmolol after intravenous administration is about 9 minutes.

The total clearance is 285 ml / kg / min, regardless of circulation in the liver or any other organ. Less than 2% of esmolol is excreted by the kidneys unchanged. The half-life of the acid metabolite of esmolol by the kidneys is about 3.7 hours, with chronic renal failure it increases by a factor of 10.

Indications:

The drug BREVIBLOCK is indicated for supraventricular tachycardia (with the exception of the ventricular pre-excitation syndrome), as well as for rapid control of the ventricular rhythm in patients with atrial fibrillation and atrial flutter during the perioperative and postoperative periods, as well as in any other situations where short-term monitoring of the ventricular contraction frequency is required using a short-acting drug.

The BREVIBLOCK preparation is also indicated for the correction of tachycardia and hypertension in the perioperative period and for sinus tachycardia of an uncompensated nature, when, in the doctor's opinion, rapid heart rate requires special intervention.

Contraindications:

- Hypersensitivity to the active substance, as well as to any of the excipients or other beta-blockers (possible cross-sensitivity between beta-blockers);

- severe form of sinus bradycardia (heart rate less than 50 beats per minute);

- syndrome of weakness of the sinus node; severe conduction disorders AV node (without a pacemaker); AV blockade of II and III degree;

- cardiogenic shock;

- severe arterial hypotension;

- Decompensated heart failure;

- simultaneous intravenous administration of blockers of "slow" calcium channels (verapamil, diltiazem). The drug BREVIBLOCK should not be administered within 48 hours after discontinuation of the administration of verapamil (see section "Interaction with other drugs");

- untreated pheochromocytoma without simultaneous use of alpha-blockers;

- pulmonary hypertension;

- acute asthmatic attack;

- metabolic acidosis;

- pregnancy;

- age to 18 years.

Carefully:

- Atrioventricular block of the 1st degree;

- bronchial asthma, chronic obstructive pulmonary disease;

- violations of peripheral circulation (Raynaud's syndrome,"intermittent" lameness);

- chronic heart failure;

- impaired renal function;

- hyperkalemia;

- thyrotoxicosis;

- psoriasis;

- myasthenia gravis;

- angina of Prinzmetal;

- hypovolemia;

- pheochromocytoma (with simultaneous use of alpha-blockers);

- elderly age;

- diabetes mellitus, and a tendency to hypoglycemia, since the drug can mask the symptoms of hypoglycemia;

- secondary arterial hypertension (due to vasoconstriction, during or after surgery, against hypothermia).

Pregnancy and lactation:

The use of BREVIBLOCK is not recommended for pregnancy.

The amount of data on the use of esmolol hydrochloride in pregnant women is limited. Studies in animals have demonstrated a negative impact on the reproductive system.

Before use, evaluate the potential risk to the fetus and benefit the mother. The use of the drug during pregnancy is possible if the probable benefit to the mother exceeds the potential risk to the fetus or the child.

If treatment is necessary, continuous monitoring of uteroplacental blood flow and fetal growth should be undertaken, as beta-blockers can reduce the blood supply of the placenta.

It was reported that the use of the drug in the second and third trimesters of pregnancy or during labor and delivery caused bradycardia of the fetus, which continued after the infusion of the drug was stopped. If pregnant women receive treatment immediately before delivery, the beta-adrenoblocking effect may persist in the newborn for several days after birth and may result in clinically significant bradycardia, respiratory distress, hypoglycemia, and hypotension. Reduced compensatory cardiovascular reactions and heart failure may require admission to the intensive care unit and neonatal monitoring.

Data on excretion of the drug with breast milk are not available, so if you need to use the drug during lactation, breastfeeding should be interrupted.

Dosing and Administration:

Only for intravenous administration!

Only for short-term use!

Do not add additional components to the container!

The dose of the drug should be selected individually based on the clinical response.Doses should be titrated, guided by the ventricular rhythm and, if necessary, arterial pressure (BP).

The drug BREVIBLOCK should be administered with caution to patients with impaired renal function (see section "Special instructions").

Supraventricular tachyarrhythmias, including atrial fibrillation and atrial flutter

The effective dose of the drug for the treatment of supraventricular tachyarrhythmia is 50-200 μg / kg / min. To control ventricular rhythm, maintenance infusion doses above 200 mcg / kg / min are not recommended; doses of more than 200 μg / kg / min provide a slight decrease in heart rate, while the frequency of adverse reactions increases. However, higher doses (250-300 μg / kg / min) may be required to adequately monitor blood pressure. The safety of doses above 300 μg / kg / min has not been studied. The dose of the drug with supraventricular tachyarrhythmia should be selected individually by titration, in which each step includes a loading dose followed by a maintenance dose.

Scheme of initiation and treatment

Administration of a loading dose of 500 μg / kg / min for 1 minute, then administering a maintenance dose of 50 μg / kg / min for 4 minutes *.

If the result is positive:

Administration of a maintenance dose of 50 μg / kg / min.

If the result is negative for 5 min:

Repeat the administration with a dose of 500 mcg / kg / min for 1 min.

Increase the maintenance dose to 100 μg / kg / min for the next 4 min.

If the result is positive:

Administration of a maintenance dose of 100 μg / kg / min.

If the result is negative for 5 min:

Repeat the administration with a dose of 500 mcg / kg / min for 1 min.

Increase the maintenance dose to 150 μg / kg / min for the next 4 min.

If the result is positive:

Administration of a maintenance dose of 150 μg / kg / min.

If the result is negative:

Repeat the administration with a dose of 500 mcg / kg / min for 1 min.

Increase the maintenance dose to 200 μg / kg / min and leave at this level.

The values of loading and maintenance doses of BREVIBLOCK, depending on the weight of the patient, are presented in Tables 1 and 2, respectively.

Table 1 - Volume of the solution of BREVIBLOK 10 mg / ml, required for administration of the INITIAL LOAD DOSE 500 μg / kg / min

Weight of the patient (kg)	40	50	60	70	80	90	100	110	120
Volume (ml)	2	2,5	3	3,5	4	4,5	5	5,5	6

Table 2 - Volume of BREVIBLOK 10 mg / ml solution needed for the administration of SUPPORTING DOSES at infusion rate of 12.5-300 μg / kg / min

The weight the patient (kg)	Infusion rate of the pillbox
	12,5 mcg / kg / min	25 mcg / kg / min	50 mcg / kg / min	100 mcg / kg / min	150 mcg / kg / min	200 mcg / kg / min	300 mcg / kg / min
	The volume of the solution administered every hour to achieve a dose infusion rate (mL / h)
40	3 ml / h	6 ml / h	12 ml / h	24 ml / h	36 ml / h	48 ml / hr	72 ml / h
50	3.75 ml / hr	7.5 ml / h	15 ml / h	30 ml / h	45 ml / h	60 ml / h	90 ml / h
60	4.5 ml / hr	9 ml / h	18 ml / h	36 ml / h	54 ml / h	72 ml / h	108 ml / hr
70	5.25 ml / hr	10.5 ml / hr	21 ml / h	42 ml / h	63 ml / h	84 ml / hr	126 ml / hr
80	6 ml / h	12 ml / h	24 ml / h	48 ml / hr	72 ml / h	96 ml / hr	144 ml / h
90	6.75 ml / hr	13.5 ml / hr	27 ml / h	54 ml / h	81 ml / hr	108 ml / hr	162 ml / h
100	7.5 ml / h	15 ml / h	30 ml / h	60 ml / h	90 ml / h	120 ml / hr	180 ml / hr
110	8.25 ml / hr	16.5 ml / hr	33 ml / h	66 ml / h	99 ml / h	132 ml / hr	198 ml / hr
120	9 ml / h	18 ml / h	36 ml / h	72 ml / h	108 ml / hr	144 ml / h	216 ml / hr

* If the desired target heart rate is reached, or the blood pressure is lowered, STOP introduction of a loading dose and reduce the rate with a sustained administration from 50 μg / kg / min to 25 μg / kg / min or lower. If necessary, the time interval between the stages of titration can be increased from 5 to 10 minutes.

Note: there is no evidence that maintenance doses above 200 μg / kg / min lead to a greater therapeutic effect. The safety of doses above 300 μg / kg / min has not been investigated.

After reaching the necessary heart rate and stable clinical state in patients with supraventricular tachycardia, it is possible to make the transition to other antiarrhythmic drugs, for example, verapamil, propranolol or metoprolol, digoxin or quinidine. At transition the attending physician should be guided by instructions on application of alternative medicinal preparations.

The dose of BREVIBLOCK should be reduced as follows:

1. Within the first hour after the first dose of the alternative drug, reduce the rate of administration of BREWBLOK in 2 times.

2. After the second dose of the alternative drug, it is necessary to monitor the patient's heart rate and, if a satisfactory heart rate is maintained during the first hour, BREVIBLOCK should be discontinued.

The administration of the drug for more than 24 hours was not evaluated. The administration of a drug lasting more than 24 hours should be performed with caution.

Tachycardia andphypertension in perioperative period

In the treatment of tachycardia and (or) arterial hypertension in the perioperative period, the following dosing regimens should be used:

a) With intraoperative treatment - with general anesthesia, when the control of the ventricular rhythm is required - to introduce a primary loading dose of 80 mg for 15-30 seconds, followed by infusion at a dose of 150 μg / kg / min.Titrate the rate of administration if necessary to 300 μg / kg / min.

b) After leaving the general anesthesia infusion at a rate of 500 μg / kg / min for 4 minutes followed by infusion of 300 μg / kg / min.

at) In the postoperative period, when time permits for dose titration, give a loading dose of 500 μg / kg / min for 1 minute before each titration step to ensure a rapid onset of action of the drug. The titration steps are 50, 100, 150, 200, 250 and 300 μg / kg / min for 4 minutes each with a stop when the desired therapeutic effect is achieved.

Additional information on doses: when therapeutic effect is achieved or blood pressure is lowered, stopping the loading dose and reducing the infusion rate to 12.5-25 μg / kg / min. In addition, if necessary, increase the time interval between the titration steps from 5 to 10 minutes.

In case of a decrease in heart rate or blood pressure below the lower limit of the norm or a rapid approach to these values, the drug should be discontinued, and after the heart rate and / or blood pressure return to a satisfactory level, the administration should be resumed at a reduced dose without loading doses.

Instruction on the use of IntraVia containers

The BREVIBLOCK preparation is a solution for infusion in a container with two PVC holes (ports): a port for extracting the primary loading dose (self-closing, polyisoprene) and a port for infusion of the drug (connection of the infusion system).

The port for extraction of the primary loading dose is used exclusively for obtaining the primary loading dose of the drug and is not intended for infusion of subsequent loading or maintenance doses.

When extracting the primary loading dose, strict adherence to aseptic rules is required.

Do not add additional components to the container!

The contents of the container are intended for single use and do not contain preservatives. After removing the protective cap from the port and starting infusion, the contents of the container should be used within 24 hours.

Dispose of unused residues.

Do not re-attach partially used containers to the infusion system.

Container Scheme IntraVia (see Figure 1).

Caveats:

- Do not connect containers together, as the ego can lead to air embolism due to the ingress of residual air from one container before the drug administration to the patient from the second container is completed.

- Do not remove the outer packaging (bag) before use. Do not use if the package is opened or partially damaged. The package protects the container from moisture penetration during storage. The sterility of the solution is provided by the integrity of the container.

- Hc it is allowed to add other preparations to the solution. The primary loading dose is extracted through the appropriate port.

Opening of the package:

- Open the bag but not cut and remove the container with the solution. Between the container and the package, condensation may form, as well as the areas of darkening of the protective laminated package and the container. This is not a deviation from the norm and does not affect the quality and safety of the drug.

- Tightly squeezing the container, you need to check it for integrity. If mechanical damage is found, the container should be disposed of, as sterility may be impaired.

- Do not use the drug in case of discoloration, cloudiness of the solution, or damage to the integrity of the package.

Preparation for infusion:

Aseptic conditions must be met.

- Hang container by special hole to support.

- Remove the plastic protective cap from the port for infusion of the drug in the bottom of the container.

- Attach the kit for insertion (follow the instructions supplied with the kit).

Side effects:

This section identifies the adverse reactions that have been recorded in patients during clinical trials and in the postmarketing period.

The frequency of adverse reactions to the drug was assessed using the following scale: very frequent (≥1/10), frequent (≥1 / 100 - <1/10), infrequent (≥1 / 1000 - <1/100), rare (≥ 1/10 000 - <1/1000) and very rare (<1/10 000). Within each grouped frequency group, undesirable effects are presented in descending order of severity.

System-Organ Class	Preferred term MedDRA	Frequency
Disorders from the metabolism and nutrition	Anorexia	Infrequent
	Hyperkalemia	--*
	Metabolic acidosis	--*
Disorders of the psyche	Depression	Frequent
	Anxiety	Frequent
	Thinking disorders	Infrequent
	Irritability	Infrequent
Disturbances from the nervous system	Confused Consciousness	Frequent
	Dizziness¹	Frequent
	Headache	Frequent
	Paresthesia	Frequent
	Attention breakdown	Frequent
	Drowsiness	Frequent
	Excitation	Frequent
	Fainting	Infrequent
	Convulsions	Infrequent
	Speech disorder	Infrequent
Disturbances on the part of the organ of sight	Visual impairment	Infrequent
Heart Disease	Bradycardia	Infrequent
	Atrioventricular block	Infrequent
	Increased pulmonary artery pressure	Infrequent
	Acute congestive heart failure	Infrequent
	Ventricular extrasystoles²	Infrequent
	Nodal rhythm	Infrequent
	Angina pectoris	Infrequent
	Sinus node stop	Rare
	Asystole	Rare
	Accelerated idioventricular rhythm	--*
	Spasm of the coronary arteries	--*
	Heart failure	--*
Vascular disorders	Arterial hypotension³	Very Frequent
	Asymptomatic arterial hypotension	Very Frequent
	Arterial hypotension with clinical manifestations	Frequent
	Peripheral ischemia	Infrequent
	Pallor	Infrequent
	"Tides" of blood to the skin of the face	Infrequent
	Thrombophlebitis⁴	--*
Disturbances from the respiratory system, chest and mediastinal organs	Dispnoe	Infrequent
	Pulmonary edema	Infrequent
	Bronchospasm	Infrequent
	Wheezing	Infrequent
	Nasal congestion	Infrequent
	Abnormal respiratory noises, including wheezing	Infrequent
Disorders from the gastrointestinal tract	Nausea	Frequent
	Vomiting	Frequent
	Disturbance of taste perception	Infrequent
	Dyspepsia	Infrequent
	Discomfort and abdominal pain	Infrequent
	Constipation	Infrequent
	Dryness of the oral mucosa	Infrequent
Disturbances from the skin and subcutaneous tissues	Increased sweating¹	Very Frequent
	Skin discoloration⁴	Infrequent
	Erythema at the site of administration⁴	Infrequent
	Necrosis of the skin⁴ (due to extravasation)	Rare
	Psoriasis⁵	--*
	Angioedema	--*
	Hives	--*
Disorders of musculoskeletal and connective tissue	Musculoskeletal pain (pain in the scapular region)	Infrequent
Disorders of musculoskeletal and connective tissue	Ridge chondrite	Infrequent
Disorders from the kidneys and urinary tract	Retention of urine	Infrequent
	Asthenia	Frequent
	Increased fatigue	Frequent
	Reactions at the injection site (in total)⁶	Frequent
	Sealing at the injection site	Frequent
	Inflammation at the site of administration	Frequent
	Chills	Infrequent
General disorders and disorders at the site of administration	Fever	Infrequent
	Edema at the site of administration⁴	Infrequent
	Pain at the injection site⁴	Infrequent
	Burning at the injection site	Infrequent
	Ecchymosis at the site of administration	Infrequent
	Phlebitis at the site of administration	--*
	Vesicles at the site of administration	--*
	Blistering⁴	--*

Note:

¹- dizziness and increased sweating combined symptomatic arterial hypotension;

² - includes increased frequency of ventricular extrasystole and dvuhdennyh ventricular extrasystoles;

³ - Based on reports of cases of arterial hypotension in eight placebo-controlled perioperative studies, arterial hypotension was less common in patients who received the drug during the perioperative period than patients who received the drug during the treatment of supraventricular tachycardia / tachyarrhythmia. Moreover, in these eight studies, the proportion (or frequency) of hypotension in patients receiving the drug and general anesthesia was the same as the proportion (or frequency) of hypotension in patients receiving placebo and general anesthesia;

⁴- in combination with local reactions in the field of injection / infusion;

⁵- beta-blockers as a class of drugs may cause psoriasis in certain situations or aggravate its treatment;

⁶- see necrosis and blistering at the injection site under "Special instructions";

* - Data for frequency estimation is not enough.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Overdose can lead to the development of life-threatening conditions and death. Some cases of severe accidental overdoses with concentrated solutions of BREVIBLOCK are described. Some of these overdoses have resulted in fatalities, and others have led to a permanent disability. Load doses ranging from 625 mg to 2.5 g (12.5 to 50 mg / kg) were lethal.

Symptoms

From the cardiovascular system: possible pronounced bradycardia, atrioventricular blockade (I, II and III degree), nodal rhythm, slowing of intraventricular conduction, decreased myocardial contractility, marked decrease in arterial pressure, acute heart failure (including cardiogenic shock), cardiac arrest, electromechanical dissociation.

From the central nervous system: possible respiratory depression, seizures, sleep and mood disorders, fatigue, inhibition, coma.Also possible bronchospasm, mesenteric ischemia, peripheral cyanosis, hyperkapemia and hypoglycemia.

From the gastrointestinal tract: nausea and vomiting are possible.

Treatment

The first step in case of symptoms of an overdose should be to stop the injection.

When bradycardia intravenous administration of atropine is indicated. Catecholamines that increase heart rate may be indicated, and / or an artificial pacemaker may be required.

When heart failure intravenous diuretics and / or cardiac glycosides are indicated.

When shock, which developed due to inadequate contractility of the myocardium, shows intravenous administration of the drug with a positive inotropic effect, for example, dopamine, dobutamine, isoprenaline, noradrenaline.

When symptomatic arterial hypotension should consider the possibility of intravenous administration of solutions to maintain the volume of circulating blood and / or vasopressor agents such as dopamine or norepinephrine.

When bronchospasm intravenously injected betaa₂-dismannymimetics and / or theophylline derivatives.

In cases of overdose, continuous monitoring of the patient is required.

Interaction:

The drug is incompatible with a 5% solution of sodium bicarbonate because of limited stability and with furosemide - due to precipitation.

With simultaneous introduction digoxin and the drug BREVIBLOCK there was an increase in the concentration in the blood of digoxin by about 10-20%. The pharmacokinetics of the drug did not change.

Combination cardiac glycosides and BREVIBLOCK can increase the time AV conductivity.

With simultaneous intravenous administration morphine and the drug there was no change in the concentration of morphine in the blood plasma, while the equilibrium concentration of esmolol in the blood increased by an average of 46%, while the other pharmacokinetic parameters remained unchanged.

When combined with antiarrhythmic drugs I class (eg, quinidine, disopyramide) or amiodarone the influence on the time of intrapartum conduction may be strengthened and the negative inotropic effect may be intensified.

Simultaneous use of the drug with other antihypertensive drugs, drugs that depress myocardial contractility, or inhibit the function of the sinus node, or conduct electrical impulses in the myocardium, can enhance the effect of the drug on blood pressure. myocardial contractility and impulses in the myocardium. Pharmacodynamic interactions with such drugs can lead, for example, to severe arterial hypotension, heart failure, severe bradycardia, sinus pause, sinouau- ricular blockade, atrioventricular block and / or cardiac arrest.

Blocks of "slow" calcium channels, such as verapamil and, to a lesser extent diltiazem, have a negative effect on contractility and AV conduction. This combination should not be administered to patients with conduction disorders. The drug BREVIBLOCK can not be administered within 48 hours after the end of the administration of the drug. Some blockers of "slow" calcium channels, for example, dihydropyridine (nifidipine) may increase the risk of hypotension. In patients with heart failure who receive calcium antagonists, treatment with beta-blockers can lead to cardiac arrest.It is recommended to thoroughly titrate the doses of BREVIBLOCK and proper hemodynamic monitoring.

In addition, the use of certain drugs against the background of beta-adrenergic blockade can lead to an increase in the syndrome of "withdrawal". In this regard, the drug should be used with caution and only after a thorough individual risk assessment and expected benefit in patients receiving drugs that can cause these types of pharmacodynamic interactions, including but not limited to the following drugs: alfuzosin. doxazosin and other alpha-blockers; amyphosgin; amiodarone; angiholin-esterase drugs; antipsychotic drugs; apomorphine; baclofen; verapamil, diltiazem and other blockers of "slow" calcium channels that inhibit cardiac activity (with joint use of the drug and verapamil in patients with decreased myocardial function, there have been cases of cardiac arrest with fatal outcome); cardiac glycosides; disopyramide, lidocaine, phenytoin, flecainide; inhalation anesthetics; levodopa; monoamine oxidase inhibitors; mefloquine; opiates, opioids, including fentanyl; barbiturates of short action; tricyclic antidepressants (for example, imipramine, amitriptyline); clonidine, guanfacine, moxonidine. The use of beta-blockers with moxonidine or alpha-2-agonists (eg, clonidine or guanfacin) increases the risk of ricochet arterial hypertension. If clonidine or moxonidine are used in combination with beta-blockers, and both effects must be stopped, first the beta-blocker is canceled, and then, after a few days, clonidine or moxonidine.

Anesthetics. In situations where the patient's volemic status is uncertain, or concomitant antihypertensive medications are used, attenuation of reflex tachycardia and an increased risk of hypotension may occur. Continued administration of beta-blockers reduces the risk of arrhythmia during induction to anesthesia and intubation. An anesthetist should be informed if the patient receives a beta-adrenergic blocking drug in addition to the BREWBLOCK preparation. The antihypertensive effect of inhalation anesthetics may be higher in the presence of BREVIBLOCK.If necessary, the doses of each drug can be changed to maintain the desired hemodynamics.

Combination of BREVIBLOCK with ganglioblocators can enhance the antihypertensive effect.

Particular care should be taken when using beta-blockers together and floktaphenine or amisulpride.

Simultaneous application of BREVIBLOCK and tricyclic antidepressants (e.g., imipramine and amitriptyline), barbiturates or phenothiazines (for example, chlorpromazine), as well as other antipsychotic agents (such as clozapine) can increase the antihypertensive effect. To avoid unexpected arterial hypotension, doses of BREVIBLOCK should be adjusted downwards.

Allergens (diagnostic or therapeutic). With the use of beta-blockers, patients at risk of anaphylactic reactions may respond more actively to the effect of an allergen (accidental, diagnostic or therapeutic). Patients who use beta-blockers may not be immune to the usual doses of epinephrine used to treat anaphylactic reactions.

Beta-blockers, including the drug BREVIBLOCK, caused muscle weakness. Therefore, beta-blockers can theoretically reduce the effectiveness anticholinesterase agents when treating muscle weakness.

Simultaneous use of beta-blockers and hypoglycemic agents for oral administration or insulin can enhance the hypoglycemic effect of the latter. Beta-adrenoblockers may mask tachycardia that occurs with hypoglycemia, although other manifestations, such as dizziness and increased sweating, may occur.

Reserpine and other drugs that deplete catecholamine stocks may have an additive effect when co-administered with beta-blockers. Therefore, patients who are co-administered with BREVIBLOK concurrently with catecholamine inhibitors should be carefully monitored for signs of arterial hypotension or severe bradycardia, which can lead to dizziness, fainting, or orthostatic arterial hypotension.

Simultaneous use of beta-blockers with derivatives of ergot alkaloids can lead to severe peripheral vasoconstriction and arterial hypertension.

Possible weakening effects glucagon, associated with an increase in the concentration of glucose in the blood.

Nonsteroidal anti-inflammatory drugs can cause a decrease in the antihypertensive effect of beta-blockers.

Effects of the drug may decrease with simultaneous use with sympathomimetic drugs, possessing the activity of beta-adrenergic agonists. The doses of each drug may need to be adjusted based on the patient's response, or alternative therapeutic agents may be considered.

The drug increases the duration of the induced succinylcholine neuromuscular blockade.

When used simultaneously with sulfinpyrazone it is possible to reduce the antihypertensive effects of beta-blockers.

The results of the study of the interaction between BREWBLOCK and warfarin showed that the simultaneous administration of the drug BREVIBLOCK and warfarin does not change the level of warfarin in the blood plasma. The concentration of esmolol when administered with warfarin tended to increase.

When studying the effect of BREVIBLOCK on the duration of neuromuscular blockade induced by suxamethonium chloride and miacuria chloride in patients undergoing surgical treatment, it was shown that the drug BREVIBLOCK did not affect the onset of neuromuscular blockade induced by suxamethonium chloride, but the duration of neuromuscular blockade increased from 5 minutes to 8 minutes. The drug BREVIBLOCK moderately increased the clinical duration of action (18.6%) and the recovery index (6.7%) of myvacuria chloride.

Although the interactions observed in studies with warfarin, digoxin, morphine, suxamethonium chloride, or myovac chloride, did not have a large clinical significance, the dose of BREVIBLOCK in patients receiving concomitantly warfarin, digoxin, morphine, suxamethonium chloride or miwakuria chloride, should be selected with caution.

Special instructions:

During the treatment it is necessary to carry out a thorough and constant monitoring of the electrocardiogram, blood pressure, heart rate.

Influence on blood pressure, heart rate, rhythm and contractility of the heart

The use of BREVIBLOCK for the control of ventricular response in patients with supraventricular arrhythmia should be conducted with caution,when the patient is hemodynamically unstable or taking other drugs that reduce all or any of the following: peripheral resistance, contractility or filling of the myocardium, the spread of an electrical impulse in the myocardium.

Undesirable reactions to beta-blockers, including BREVIBLOCK, from the heart and blood vessels may be severe, especially in patients with hemodynamic disorders and patients taking drugs that increase the risk of cardiovascular reactions. Severe reactions may include severe arterial hypotension, severe bradycardia, sipoauric blockade, atrioventricular block and / or cardiac arrest, cardiogenic shock, which can lead to death.

The drug BREVIBLOCK, in the absence of contraindications (see the section "Contraindications"), should be used with caution and only after a thorough individual risk assessment and the expected benefit in patients with hemodynamic disorders and patients at increased risk due to possible drug interactions.

When the drug was used, arterial hypotension, including heavy.Arterial hypotension depends on the dose (see sections "Method of administration and dose" and "Side effect"). Careful monitoring of patients should be carried out, especially in the case of low blood pressure before starting treatment. In the case of a sharp decrease in blood pressure should reduce the dose of the drug or stop its introduction. Arterial hypotension, as a rule, passes within 30 minutes after discontinuation of the drug administration. In some cases, additional treatment may be required.

When using the drug, we observed bradycardia, including severe bradycardia, and cardiac arrest. The drug should be used with extreme caution in patients with low heart rate before treatment and only when it is believed that the potential benefit exceeds the risk. The drug is contraindicated in patients with existing severe sinus bradycardia (see section "Contraindications"). In case of symptomatic bradycardia with heart rate at rest below 50-55 beats / min, the dose of the drug should be reduced or its administration should be stopped.

Beta-adrenoblokada reduces myocardial contractility and can provoke or aggravate the course heart failure. At the first sign of heart failure should reduce the dose of the drug or stop its introduction. In some cases, additional treatment may be required. Care should be taken when using the drug in patients with impaired cardiac function (the drug is contraindicated for use in patients with severe heart failure or cardiogenic shock - see the section "Contraindications").

Beta-adrenoblockers affect the function of the sinus node, as well as sinus-atrial and atrial-ventricular conduction, and can lead to the development syndrome of sinus node weakness, sinoatrial and atrioventricular blockade, including a complete blockade, which can lead to cardiac arrest. This effect is most typical for patients with already existing sinus node dysfunction and conduction disorders (the drug is contraindicated in patients with AV blockade of II or III degree and in patients with sinus node weakness syndrome - see the section "Contraindications"). The drug should be used with caution in patients with other cardiac conduction disorders, including atrioventricular blockade of the I degree.

The drug should be used with caution in patients with pheochromocytoma and only with the simultaneous use of α-adrenoreceptor blockers (see the section "Contraindications").

The drug BREVIBLOCK should be used with caution as an agent for treatment arterial hypertension in patients whose elevated blood pressure is mainly due to vasoconstriction on the background of hypothermia.

The drug BREVIBLOCK should also be used with caution in patients with bronchial asthma and other obstructive bronchial diseases in the anamnesis. Patients with bronchospastic syndrome should not receive beta-blockers. The drug BREVIBLOCK, due to its relative β₁-selectivity and titrimosti, can be used with caution in patients with bronchospastic syndrome. However, since β₁-selectivity is not absolute, exact dosing of the drug is required to achieve the lowest possible effective dose. In the case of bronchospasm or deterioration in the current bronchospasm, stop the infusion immediately; if the condition allows, perhaps an appointment β₂-adrenomimetic drugs.

The drug should be used with caution in patients prone or prone to hypoglycemia, as well as in patients with diabetes mellitus, who receive insulin or hypoglycemic agents for oral administration. Beta-adrenoblockers may mask tachycardia that occurs with hypoglycemia, although other manifestations, such as dizziness and increased sweating, may occur. The concomitant use of beta-blockers and hypoglycemic agents may exacerbate the hypoglycemic effect of the latter (see also the section "Interaction with other drugs").

When using the drug BREVIBLOCK observed reaction at the site of administration. They included both symptoms of irritation and inflammation at the site of infusions, as well as more serious reactions in the form of thrombophlebitis, necrosis, the formation of blisters, especially in cases of extravasation (see section "Side effect"). Avoid infusions into small veins and using a butterfly catheter. If there is a local reaction in the infusion area, another place should be used for infusion.

Because of the risk of reducing heart contractility against a background of high systemic vascular resistance, the drug should not be used to control tachycardia in patients receiving drugs that have vasoconstrictive and positive inotropic effects, including epinephrine, norepinephrine, dopamine.

Beta-blockers can increase the number and duration of angina attacks in patients with Prinzmetal angina due to unimpeded α-adrenoreceptor mediated spasm of the coronary artery. For such patients, non-selective beta-blockers should not be used, and selective beta-blockers₁- adrenoblockers - only with special precautions.

In patients with hypovolemia the drug can weaken reflex tachycardia and increase the risk of hypotension. In this regard, in such patients the drug should be used with special precautions.

Since it is impossible to exclude withdrawal syndrome, as well as for all beta-blockers, caution should be exercised with a sharp discontinuation of the administration of the drug to patients with ischemic heart disease.In a clinical electrophysiological study, the heart rate after 30 minutes after the drug was withdrawn was slightly, but significantly higher than the original one.

Patients with violations of peripheral circulation (including Raynaud's disease or syndrome and peripheral vascular occlusive disease), the drug should be used with caution, since beta-blockers can enhance peripheral circulatory disturbances.

The drug should be administered with caution to patients from impaired renal function. Acid metabolite of the drug is excreted by the kidneys mainly unchanged. His excretion is significantly reduced in patients with kidney disease. In patients with terminal stage of renal failure, its half-life increases by 10 times, and the level in the blood plasma increases significantly.

The use of beta-blockers, including the drug BREVIBLOCK, was accompanied by an increase in the content of potassium in the blood plasma and hyperkalemia. The risk increases if patients have such factors as renal failure. It has been reported that intravenous administration of beta-blockers causes potentially life-threatening hyperkalemia in patients on hemodialysis.

It was reported that beta-blockers, including BREVIBLOCK, cause or contribute to the development hyperkalemic renal tubular acidosisa. In addition, acidosis can usually be accompanied by reduced myocardial contractility. The drug should be used with caution in patients with previous acidosis.

Beta-adrenergic blockade may mask some clinical signs hyperthyroidism (for example, tachycardia). A sharp cessation of beta-adrenergic blockade can provoke a thyrotoxic crisis. In this connection, it is necessary to carefully monitor patients who are expected to develop thyrotoxicosis when beta-blockers are discontinued.

When beta-blockers are used, patients with an increased risk of anaphylactic reactions can respond more actively to the effects of the allergen (random, diagnostic or therapeutic).

Patients who use beta-blockers may not be immune to the usual doses of epinephrine (adrenaline) used to treat anaphylactic or anaphylactoid reactions (see also "Interactions with Other Drugs").

The use of beta-blockers was accompanied by the development of psoriasis or psoriaziformnyh rashes and exacerbation of psoriasis. In patients with psoriasis, a history of beta-blockers should be prescribed only after a thorough analysis of the expected benefits and risks.

Beta-blockers, including BREVIBLOCK, caused muscle weakness. The drug should be used with caution in patients with muscle weakness.

Elderly patients The drug should be administered with caution. Generally, dose selection for an elderly patient should be carried out with caution, usually starting from a low dose range, taking into account the greater frequency of reduced renal or cardiac function, concomitant diseases, or other medications.

Because the drug is metabolized by erythrocyte esterases, no special precautions are taken in patients with hepatic insufficiency not required.

The drug BREVIBLOCK contains about 30.45 mmol (or 700 mg) of sodium in one container. This should be borne in mind when appointing a diet with sodium content control.

Effect on the ability to drive transp. cf. and fur:

Some of the undesirable effects that occur after the use of the drug, such as dizziness or drowsiness, can affect a patient's ability to drive vehicles and work with mechanisms. Patients should not drive vehicles or operate machinery until such effects disappear.

Form release / dosage:Solution for infusion, 10 mg / ml.

Packaging:

250 ml of the drug in containers Intra Via with two PVC-holes (ports).

Each container is sealed in a protective laminated package.

Each container in a protective laminated package, together with the instruction for use, is placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:For hospitals

Registration number:LP-001060

Date of registration:27.10.2011 / 28.10.2016

Expiration Date:Unlimited

The owner of the registration certificate:Baxter Helskea LimitedBaxter Helskea Limited United Kingdom

Manufacturer: & nbsp

BAXTER, S.A. Belgium

Representation: & nbspBaxter Baxter USA

Information update date: & nbsp17.04.2017

Illustrated instructions

Instructions

Breviblock (Brevibloc)