Atrakurium-Novo - instructions for use, doses, side effects, contraindications

Atracuria bezylate is a highly selective, non-depolarizing muscle relaxant of a competitive type of action. Atracuria bezylate reduces the sensitivity of the H-holinoretseptora synaptic region to acetylcholine, which makes it impossible to stimulate the muscle fiber and reduce it. Promotes the release of histamine.

Pharmacodynamic effects

Atracuria besylate does not have a direct effect on intraocular pressure. In this way, atracurium bezylate is applicable in ophthalmic surgical practice.

Pharmacokinetics:

Metabolism

Atracurium bezylate is inactivated by elimination of Hofmann (a process that occurs at physiological pH and temperature values without the participation of enzymes) and by ether hydrolysis with the participation of nonspecific esterases. Plasma studies in patients with a low level of pseudocholinesterase showed that the products of atra- caria bezilate metabolism do not change.

Changes in the pH values of the blood and body temperature in the physiological limits have a slight effect on the duration of action of atracurium bezylate.

Excretion

The duration of neuromuscular blockade caused by the administration of atracurium bezilate is not dependent on its metabolism in the liver or kidneys or excretion. Therefore, it is unlikely that the duration of action of the drug varies with violations of the kidneys, liver or circulatory disorders.

Special patient groups

Hemofiltration and hemodiafiltration have a minimal effect on the concentrations of atracurium besylate and its metabolites (including laudanosine) in the blood plasma. About influence hemodialysis and hemoperfusion at the concentration of atracurium besylate and its metabolites in blood plasma is unknown.

Patients in the intensive care unit with impaired renal and / or liver function experienced higher concentrations of atra- kurium besylate metabolites. Metabolites have no effect on neuromuscular conduction.

Indications:

As a component of general anesthesia for providing intubation of the trachea and relaxation of skeletal muscles in surgical interventions or controlled ventilation of the lungs and for facilitating the carrying out of artificial ventilation in patients in intensive care units (ICU).

Contraindications:

Hypersensitivity to atrakury bezilate, cisatracurium bezylate, benzenesulfonic acid, any other components of the drug.

Children: the period of newborns (up to 1 month).

Known hypersensitivity to histamine.

Pregnancy and lactation:

Fertility

The effect on fertility has not been studied.

Pregnancy

Animal studies have shown that the use of atracurium bezilate does not have a significant effect on fetal development.

Like other muscle relaxants, the drug Atracurium-Novo should be used during pregnancy only if the potential benefit to the mother exceeds any possible risk to the fetus.

Atracuria bezilat can be used for the purpose of muscle relaxation during a caesarean section, since when administered at recommended doses atracurium bezylate It does not penetrate the placental barrier in clinically significant amounts.

Breastfeeding period

There are no data on the penetration of atracurium bezilate into breast milk.

Dosing and Administration:

The table of pharmaceutical compatibility of the drug Atrakurium-Novo with some infusion solutions is given in the section "Interaction with other medicinal products".

Adults

Injectable use in adults

Enter intravenously in the form of injections. For adults, the dose range is 0.3 to 0.6 mg / kg (depending on the required duration of a complete blockade), which provides adequate myoplegia during 15-35 min.

After intravenous administration at doses of 0.5 to 0.6 mg / kg, endotracheal intubation can be performed, as a rule, after a lapse of 90 seconds.

If it is necessary to prolong the complete neuromuscular blockade, the drug is additionally administered in a dose of 0.1-0.2 mg / kg. The correct administration of additional doses of the drug does not result in a cumulation of the myorelaxing effect.

Spontaneous recovery of conduction after complete neuromuscular blockade occurs in approximately 35 min, which is determined by restoring the tetanic contraction to 95% of the normal neuromuscular function. Neuromuscular blockade caused by atracurium can be quickly eliminated by the use of anticholinesterase agents in standard doses such as neostigmine and eudrophonia, combined with simultaneous or preliminary administration of atropine (without the appearance of signs of recurrence).

Infusion use in adults

After an initial bolus dose of 0.3-0.6 mg / kg of the drug, it can be used to maintain neuromuscular blockade during prolonged surgical intervention by prolonged infusion at a rate of 0.3 to 0.6 mg / kg / h.

The drug can be administered by infusion during cardiovascular surgery by shunting at the rate recommended for infusion.With induced hypothermia with a body temperature of 25 to 26 ° C, the rate of inactivation of the drug decreases, thus, in order to maintain complete miorelaxation at low temperatures, the infusion rate is reduced approximately 2-fold.

Children

For children aged 2 years and older, the drug is prescribed in the same doses as for adults, in terms of body weight.

The initial dose of the drug used in children aged 1 month to 2 years with halothane anesthesia is 0.3-0.4 mg / kg. Children may need more frequent use of maintenance doses than adults.

Elderly patients

The drug can be used in standard doses in elderly patients. However, it is recommended to use the initial dose, which is less than the lower value of the dose range, and inject the drug slowly.

Patients with impaired hepatic and / or renal function

The drug can be used in standard doses for any degree of impaired liver and / or kidney function, including end-stage failure.

Patients with cardiovascular diseases

In patients with cardiovascular diseases with severe clinical symptoms, the initial dose of the drug should be administered within 60 seconds.

Application in intensive care units

After the administration of the drug in the initial bolus dose of 0.3-0.6 mg / kg, if necessary, it can be used to maintain neuromuscular blockade by prolonged infusion at a rate of 11-13 μg / kg / min (0.65-0.78 mg / kg / h). However, there are wide interindividual differences in the dosing regimen. Dosage regimen can vary with time. Some patients may require both a low infusion rate of 4.5 μg / kg / min (0.27 mg / kg / h) and a high infusion rate of 29.5 μg / kg / min (1.77 mg / kg / hr ).

The rate of spontaneous recovery after neuromuscular blockade at the end of drug infusion in OPT patients does not depend on the duration of administration. Spontaneous recovery of neuromuscular conduction (the ratio of the height of the quarter to the first twitch in the test train-of-the four T₄/ T₁ > 0.75) usually occurs after about 60 minutes. In clinical trials this period was from 32 up to 108 min after the infusion of atracurium bezylate, and its rate does not depend on the duration administration of the drug.

Instruction for breeding

Atracuria besylate is compatible with the following infusion solutions:

Infusion solutions	Stability period, h
Sodium chloride solution for intravenous infusion 0.9%	24 hours
Dextrose solution for intravenous infusion 5%	8 ocloc'k
Ringer's injection solution	8 ocloc'k
A solution of sodium chloride 0.18% and dextrose 4% for intravenous infusions	8 ocloc'k
Hartman Solution for Injection	4 hours

When diluted with compatible infusion solutions to obtain atrakurium besylate concentration of at least 0.5 mg / ml, the solution remains stable for a specified period of time under normal lighting and at temperatures up to 30 ° C.

Side effects:

The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems of frequency of occurrence. Frequency of occurrence is defined as follows: Often (≥ 1/10), often (≥ 1/100 and <1/10), infrequently (≥ 1/1000 and <1/100), rarely (≥ 1/10 000 and <1/1000), rarely (< 1/10 000), unknown (the frequency can not be set based on the available data). Frequency categories "very often", "often" and "infrequently" were formed on the basis of clinical studies of atracurium bezilate. Frequency categories "rarely", "very rarely" were formed on the basis of spontaneous messages.

Clinical Trials Data

Vascular disorders

Often: lowering blood pressure (light, transient) *, skin hyperemia *.

Disturbances from the respiratory system, chest and mediastinal organs

Infrequently: bronchospasm *.

* - undesirable reactions associated with the release of histamine.

Post-registration data

Immune system disorders

Rarely: anaphylactic and anaphylactoid reactions, including shock, circulatory failure and cardiac arrest. Very rarely reported severe anaphylactic and anaphylactoid reactions in patients taking atracurium bezylate in combination with one or more anesthetics.

Disturbances from the nervous system

Unknown: convulsions.

There were reports of cases of seizures in patients in the ICU who were taking atracurium bezylate in combination with some other drugs. Typically, these patients had one or more conditions predisposing to the occurrence of seizures, such as head trauma, cerebral edema, viral encephalitis, hypoxic encephalopathy, uremia. The causal relationship between the onset of seizures and laudanosin is not established.As a result of clinical the correlation between plasma concentrations of laudanosine and the occurrence of seizures is absent.

Disturbances from the skin and subcutaneous tissues

Rarely: urticaria.

Disturbances from musculoskeletal and connective tissue

Unknown: myopathy, muscle weakness.

Several cases of myopathy and / or muscle weakness have been reported with long-term use of muscle relaxants in severely ill patients in ICU. Most of them simultaneously received glucocorticosteroids. These undesirable reactions were rare, the cause-and-effect relationship with the use of atracurium bezilate was not established.

Overdose:

Symptoms: Prolonged muscular paralysis and its consequences.

Treatment: Ventilator under positive pressure to restore spontaneous breathing. It is necessary to use sedatives, because the consciousness of patients is not violated.

As soon as signs of spontaneous recovery appear, it can be accelerated with anticholinesterase drugs in combination with atropine or glycopyrrolate.

Interaction:

Atrakurium-induced besylate neuromuscular blockade may be exacerbated by the use of agents for inhalation anesthesia, such as halothane, isoflurane, enflurane.

As with other non-depolarizing muscle relaxants, it is possible to increase the intensity and / or duration of the neuromuscular blockade as a result of interaction with the following drugs:

- antibiotics, including aminoglycosides, polymyxins, spectinomycin, tetracyclines, lincomycin and clindamycin;

- antiarrhythmics: propranolol, calcium channel blockers, lidocaine, procainamide and quinidine;

- diuretics: furosemide and, perhaps, mannitol, thiazide diuretics and acetazolamide;

- magnesium sulfate;

- ketamine;

- lithium salts;

- ganglion blockers: trimetaphane, hexamethonium.

In rare cases, certain drugs cause an exacerbation of myasthenia, contribute to the development of myasthenia from the latent form, as well as the myasthenic syndrome, in which it is possible to increase the sensitivity to atracurium bezilate. These drugs include various antibiotics, beta-blockers (propranolol, oxprenolol), antiarrhythmic (procainamide, quinidine) and antirheumatic drugs (chloroquine, D-phenicylamine), trimetaphane, chlorpromazine, steroids, phenytoin and lithium salts.

The development of neuromuscular blockade caused by nondepolarizing muscle relaxants is likely to slow down, and its duration decreases in patients receiving anticonvulsant therapy for a long time.

The combined use of nondepolarizing neuromuscular blockers and atracurium bezilate may cause excessive blockade compared with the expected one-atrachium besylate in an equipotential cumulative dose. Any effect due to synergism can change with different combinations of drugs. Depolarizing muscle relaxant suxamethonium chloride It should not be used to prolong the neuromuscular blockade caused by nondepolarizing muscle relaxants, such as atracurium bezylate, as this can cause prolonged complex blockade, which is difficult to suppress with anticholinesterase agents.

Therapy with anticholinesterase drugs, often used to treat Alzheimer's disease, for example, donepezil, can shorten the duration of neuromuscular blockade and weaken the blocking effect of atracurium bezylate. Pharmaceutical compatibility

The drug Atrakurium-Novo is compatible with the following solutions for infusions (at a concentration of 0.5 to 0.9 mg / ml in daylight and temperature to 30 ° C): 0.9% sodium chloride solution for intravenous administration - for at least 24 h; 5% dextrose solution for intravenous administration -8 hours; Ringer's injection for 8 h; solution of sodium chloride 0.18% and dextrose 4% for intravenous administration -8 h; Hartman solution for intravenous administration -4 hours.

Special instructions:

Like other muscle relaxants, atracurium bezylate causes paralysis of the respiratory muscles, as well as skeletal muscles, but does not affect consciousness. Atracuria bezylate should be administered only with general anesthesia under the careful supervision of a qualified anesthesiologist with equipment for intubation of the trachea and ventilation.

In predisposed patients atracurium bezylate can cause the development of reactions associated with the release of histamine. Caution should be exercised when administering atracurium bezilate to patients with a history of hypersensitivity to histamine effects.In particular, bronchospasm may occur in patients with a history of allergy or bronchial asthma.

Caution is also required when atracurium bezilate is administered to patients who have experienced hypersensitivity reactions to other muscle relaxants, since a high incidence of cross-sensitivity between muscle relaxants (> 50%) has been identified (see "Contraindications").

For patients suffering from bronchial asthma who receive high doses of glucocorticosteroids and muscle relaxants in the OPT, the possibility of multiple monitoring of creatinephosphate kinase (CK) content should be considered.

When used in the recommended dose range atracurium bezylate does not cause a significant blockade of the vagus nerve and nerve ganglia. Consequently, atracurium bezylate in the recommended dose range does not have a clinically significant effect on the heart rate and does not prevent bradycardia caused by many anesthetics or vagal nerve stimulation during surgery.

As with the use of other nondepolarizing muscle relaxants, hypophosphatemia may slow the recovery.Recovery can be accelerated by correcting this state.

As with other muscle relaxants, severe acid-base balance disorders and / or impaired balance of blood serum electrolytes may increase or decrease the sensitivity of patients to the drug.

As with other non-depolarizing muscle relaxants, hypersensitivity to atracurium bezilate can be observed in patients with severe myasthenia gravis, other neuromuscular diseases and severe electrolyte imbalance.

Patients with a tendency to a sharp decrease in blood pressure, for example, with hypovolemia, atracurium bezylate it is recommended to enter for more than 60 seconds. Atracuria bezylate is inactivated in an alkaline medium, and therefore the drug should not be mixed in one syringe with thiopental or any alkaline solutions.

If the drug is administered into a vein of small caliber, then after injection, it should be washed with saline. When other anesthetics are injected through the same injection needle or cannula, it is important that each preparation is rinsed with an appropriate amount of saline.

The solution of atracurium besylate is hypotonic, and it can not be administered simultaneously through a single system with blood transfusion.

Studies of malignant hyperthermia in predisposing animals (pigs) and clinical studies in patients susceptible to malignant hyperthermia show that atracurium bezylate does not cause this syndrome.

As with other non-depolarizing muscle relaxants, patients with burns may develop resistance when prescribing the drug. In such cases, an increase in the dose may be required, the magnitude of which depends on the time elapsed after the burn, and on the surface area of the burn.

Patients in the OPT: the introduction of laboratory animals in large doses of laudanosine, the metabolite of atracurium bezilate, was associated with a transient decrease in blood pressure, and in some species of animals with cerebral stimulatory effects. Patients in the OPT who received atracurium bezylate, convulsions were noted, however, the cause-and-effect relationship of their development with laudanosine (metabolite of atracurium bezilate) is not established (see the "Side effect" section).

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

This indication is unacceptable when using the drug Atrakurium-Novo, since it is always used only for general anesthesia.

Form release / dosage:Solution for intravenous administration 10 mg / ml.

Packaging:

For 5 ml in a glass vial, ukuporennyh a stopper rubber and the crimped cap aluminum. 5 bottles in a planar cell package. 1 contour pack together with instructions for medical use in a pack of cardboard.

Storage conditions:

In the original packaging at a temperature of 2 to 8 ° C. Do not freeze. Keep out of the reach of children.

The solution of atracurium besylate, which has not been used after opening the bottle, must be destroyed.

Shelf life:2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004394

Date of registration:01.08.2017

Expiration Date:01.08.2022

The owner of the registration certificate:Novofarm-Biosintez firm, Open CompanyNovofarm-Biosintez firm, Open Company Ukraine

Manufacturer: & nbsp

Novofarm-Biosintez firm, Open Company Ukraine

Information update date: & nbsp12.09.2017

Illustrated instructions

Instructions

Atracurium-Novo (Atracurium-Novo)