Notriksum - instructions for use, dose, side effects, contraindications

Atracuria besylate is a highly selective, competitive, nondepolarizing muscle relaxant of peripheral action, reducing the sensitivity of n-cholino receptors of skeletal muscles to acetylcholine, blocking neuromuscular transmission, causing temporary relaxation of skeletal muscles (including respiratory). It has a rapid onset of action (within 2-2.5 minutes), which allows intubation of the trachea in the first 90 seconds from the moment of its administration at a dose of 0.5-0.6 mg / kg.The speed of development of the neuromuscular blockade of the vocal cords of the larynx, necessary for intubation of the trachea, vecuronium bromide and pancuronium bromide. In a dose of 0.2-0.6 mg / kg, the expected relaxation of skeletal muscles, which is proportional to the amount administered, is 20-35 min. The miorelaksiruyuschee action comes and stops faster than with the introduction of pancuronium bromide. The rate of recovery of the neuromuscular transmission after the administration of atracurium bezylate (single and repeated) is constant, which allows the administration of repeated doses at predetermined time intervals. Restoration of normal neuromuscular transmission without the use of cholinesterase inhibitors occurs after 35 min and does not depend on the total dose and the function of the excretory and metabolism organs. The onset of action is 2-5 times faster than other nondepolarizing muscle relaxants.

In therapeutic doses, it has insignificant m-cholino-and ganglion-blocking activity. Promotes the release of histamine.

Atracuria besylate does not have a direct effect on intraocular pressure.

In this way, atracurium bezylate is applicable in ophthalmic surgical practice.

Pharmacokinetics:

The time to reach the maximum concentration (Tmah) in the plasma - 1.7-10 minutes (average - 3-5 minutes).

The connection with plasma proteins is high (about 80%). The half-distribution period is 2-3.4 min. Do not penetrate the placental barrier at clinically significant concentrations. The duration of neuromuscular blockade does not depend on the intensity of hepatic metabolism and the rate of excretion by the kidneys. At physiological values, the pH of the blood and body temperature without the participation of enzymes is metabolized (Hoffman elimination) to laudanosine and quaternary monoacrylate; in a small degree hydrolyzed by plasma esterases, therefore the duration of action does not depend on the function of the liver and kidney. Metabolites are pharmacologically inactive. Physiological changes in blood pH have little effect on the duration of the action. Under hypothermia (body temperature 25-26 ° C), the metabolic rate decreases. Plasma studies in patients with low pseudocholinesterase activity have shown that the products of atra- caria bezilate metabolism do not change. Do not cumulate. The half-life (T1 / 2) is 20 min.

It is excreted by the kidneys and with bile (less than 10% - unchanged).

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

In patients with impaired renal and / or liver function, higher concentrations of atra- kurium besylate metabolites were observed.

Indications:

Miorelaxation for intubation of the trachea and artificial ventilation (IVL) during surgery and for ventilation in intensive care units (ICU).

Contraindications:

Hypersensitivity to atracurium bezilate, cisatracurium bezilate or benzylsulfonic acid.

Hypersensitivity to histamine.

Carefully:

In predisposed patients, Notriksum may cause the development of reactions associated with the release of histamine. Caution should be exercised when administering the drug Notriksum to patients with histamine hypersensitivity in the anamnesis.

In patients with hypersensitivity reactions to other muscle relaxants,also it is necessary to be careful with the introduction of the drug Notriksum, since a high frequency of occurrence of cross-sensitivity between muscle relaxants (more than 50 %) (see section "Contraindications"). As with other non-depolarizing muscle relaxants, increased sensitivity to drug Notrixum can be observed in patients with severe myasthenia gravis gravis, other neuromuscular diseases and severe electrolyte imbalance.

Pregnancy and lactation:

The use of the drug during pregnancy and during breastfeeding is possible only if the expected benefit for the mother exceeds the potential risk to the fetus and the baby.

Notriksum can be used for the purpose of miorelaxation in the operation of cesarean section, since when administered at recommended doses atracurium bezylate penetrates the placental barrier in clinically insignificant amounts.

It is not known whether the atracurium bezylate and its metabolites into breast milk.

Dosing and Administration:

Intravenous (bolus or infusion).

The dose is set individually and depends on the necessary duration and depth of the neuromuscular blockade.To determine the individual dose should be monitored neuromuscular function during the entire period of application of the drug.

Adults

Bolus injection

By 0,3-0,6 mg / kg (depending on the required duration of the complete block) provides relaxation for 15-35 minutes.

Conduction of endotracheal intubation is possible within 90 s after intravenous injection of 0.5-0.6 mg / kg.

The duration of complete neuromuscular blockade can be increased by introducing an additional dose of atracurium bezilate at a rate of 0.1-0.2 mg / kg, which is not accompanied by a cumulation of its action. Neuromuscular conduction can be quickly restored by standard doses of cholinesterase inhibitors (neostigmine methylsulfate and others) in combination with atropine (without the appearance of signs of recurrence).

Infusion introduction

After initial bolus administration of the drug at a dose of 0.3-0.6 mg / kg, it can be administered by continuous intravenous infusion at a rate of 0.3-0.6 mg / kg / hr to maintain neuromuscular blockade during prolonged surgical operations. The drug can be used by intravenous infusion during coronary artery bypass grafting.Induced hypothermia of the body to a temperature of 25-26 ° C leads to a decrease in the rate of inactivation of atracurium bezilate, therefore, in order to maintain complete neuromuscular blockade, the rate of infusion of the drug should be reduced approximately 2-fold.

Atracuria besylate is compatible with the following infusion solutions:

Infusion solutions	Stability period, h
A solution of sodium chloride (0.9%)	24 hours
A solution of dextrose (5%)	8 ocloc'k
Ringer's solution	8 ocloc'k
A solution of sodium chloride (0.18%) and dextrose (4%)	8 ocloc'k
Hartmann's solution	4 hours

When diluted in the above solutions until atraquarium at least 0.5 mg / ml is obtained, the solution remains stable for a fixed period of time under normal illumination and at temperatures above 30 ° C.

Children

The initial dose of the drug in children aged 1 month to 2 years with halothane anesthesia is 0.3-0.4 mg / kg.

Children aged 2 years or older receive the drug in adult doses in terms of body weight.

Children may need more frequent use of maintenance doses than adults.

Elderly patients

It is used in doses for adults, but the initial dose is recommended to be reduced to a minimum therapeutic dose and injected more slowly.

Patients with impaired hepatic and / or renal function

If the liver and / or kidney function is impaired, including at the terminal stage of hepatic or renal insufficiency, the drug is prescribed in standard doses.

Patients with diseases of the cardiovascular system

For patients with severe cardiovascular failure, the initial dose of the drug should be administered for at least 60 seconds.

Application in intensive care units

After initial bolus administration of the drug at a dose of 0.3-0.6 mg / kg, it can be administered by continuous infusion at a rate of 11-13 μg / kg / min (0.65-0.78 mg / kg / h). In different patients, the dose is not the same and may change over time. Some patients may require a dose reduction of 4.5 μg / kg / min (0-7 mg / kg / h) or an increase of up to 29.5 μg / kg / min (1.77 mg / kg / h).

Spontaneous recovery of neuromuscular conduction (achieving a T4 / T1 ratio of 0.75, i.e. 4 shortening of 2 Hz every 0.5 seconds, a ratio of the 4th contraction to the 1st should be> 0.75) usually occursapproximately 60 minutes (during clinical trials this period was 32 to 108 minutes) after the infusion of the drug and does not depend on the duration of its use.

Side effects:

The undesirable phenomena presented below are listed by the system-organ classes and frequency of occurrence. Frequency of occurrence is defined as follows: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (> 1/10 000 and < 1/1000), very rarely (<1/10 000, including individual cases), the frequency is unknown (can not be estimated from the available data). Frequency categories "very often", "often" and "infrequently" were formed on the basis of clinical studies. Frequency categories "rarely", "very rarely" were formed on the basis of spontaneous messages.

Clinical Trials Data

From the side of the cardiovascular system

Often: transient reduction in blood pressure, skin hyperemia.

On the part of the respiratory system, the organs of the thorax and the mediastinum

Infrequent: bronchospasm.

The above undesirable phenomena are associated with the release of histamine.

Post-registration data

From the immune system

Very rarely: anaphylactic and anaphylactoid reactions.

Very rarely reported severe anaphylactic or anaphylactoid reactions with simultaneous use of atracurium bezilate with anesthetics.

From the nervous system

The frequency is unknown: convulsions.

There have been reports of cases of seizures in patients on intensive care (receiving combination therapy, including atracurium bezylate). Typically, these patients had a predisposition to developing seizures, including head trauma, cerebral edema, viral encephalitis, hypoxic encephalopathy, or uremia. The relationship between the onset of seizures and laudanosine (the metabolite of atracurium bezylate) has not been established. According to the results of the clinical study, there is no correlation between plasma concentrations of laudanosine and the occurrence of seizures.

From the skin and subcutaneous fat

Rarely: urticaria.

From the side of the musculoskeletal system and connective tissue

HThe astota is unknown: myopathy, muscle weakness.

Several cases of myopathy and / or muscle weakness have been reported with long-term use of muscle relaxants in critically ill patients in the intensive care unit.Most of them simultaneously received glucocorticosteroids. This side reaction is regarded as uncharacteristic of atractionsurThe relationship with the use of the drug has not been established.

Overdose:

Symptoms: long paralysis of skeletal muscles and its consequences are the main signs of an overdose.

Treatment: great importance is to ensure the patency of the airways and performing artificial ventilation of the lungs under positive pressure to restore adequate spontaneous breathing. It is necessary to use sedatives, because the consciousness of patients is not violated. When the spontaneous recovery of neuromuscular conduction begins, it can be accelerated with the help of cholinesterase inhibitors in combination with atropine.

Interaction:

Neuromuscular blockade caused by atracurium bezilate can be intensified by the use of halothane, isoflurane, enflurane.

It is possible to intensify the intensity and duration of the neuromuscular blockade caused by nondepolarizing muscle relaxants, including atracurium bezylate, while using several antibiotics (aminoglycosides, polymyxins, spectinomycin, tetracycline, lincomycin and clindamycin); antiarrhythmic drugs (propranolol, blockers of "slow" calcium channels, lidocaine, procainamide and quinidine); diuretics (furosemide and, perhaps, mannitol, thiazides, acetazolamide); magnesium sulfate; ketamine; lithium salts: ganglion blockers (trimetaphane camsilate, hexamethonium benzenesulfonate).

With simultaneous use with drugs that can enhance the manifestations of myasthenia gravis (including latent flow) and provoke the development of myasthenic syndrome, it is possible to increase sensitivity to atracurium bezilate. These drugs include antibiotics, β-adrenoblockers (propranolol, oxprenolol), antiarrhythmic agents (procainamide, quinidine), antirheumatic drugs (chloroquine, penicillamine), trimetaphane camsylate, chlorpromazine, steroid hormones, phenytoin and lithium salts.

The introduction of other non-depolarizing muscle relaxants in combination with atrakury besylate can cause a more pronounced neuromuscular blockade compared with the expected one-atrachium ate equivalent at the equivalent total dose.The synergistic effect may vary depending on the combination of drugs.

When using depolarizing muscle relaxants (for example, suxamethonium chloride) with the aim of increasing the duration of the neuromuscular blockade caused by nondepolarizing muscle relaxants, including atracurium bezylate, it is possible to develop a long and deep miorelaxation, which is difficult to eliminate with cholinesterase inhibitors.

Therapy with cholinesterase inhibitors used to treat Alzheimer's disease (eg, donepezil), can shorten the duration of neuromuscular blockade and weaken the muscle relaxant effect of atracurium bezilate.

Special instructions:

Like other muscle relaxants, atracurium bezylate causes paralysis of skeletal muscles, including respiratory, but does not affect consciousness. Atracuria bezylate should be used only during general anesthesia under the supervision of a qualified anesthesiologist in departments where there is equipment for intubation of the trachea and artificial ventilation.

As with the use of other muscle relaxants, in predisposed patients atracurium bezylate can cause the development of reactions associated with the release of histamine, so it should be administered with caution in hypersensitivity to histamine in history.

When administered at the recommended dose range atracurium bezylate does not block the vagus nerve and nerve ganglia, has no clinically significant effect on the heart rate and does not prevent bradycardia caused by anesthetics or vagal nerve stimulation during surgery.

As with the use of other nondepolarizing muscle relaxants, hypersensitivity to atracuria can be observed in patients with myasthenia gravis, other neuromuscular diseases and with severe electrolyte disturbances balance. The development of neuromuscular blockade caused by nondepolarizing muscle relaxants, slows down, and its duration decreases in patients receiving long-term anticonvulsant therapy.

Neuromuscular blockade is quickly and completely eliminated by neostigmine methylsulfate and the preceding administration of atropine (after 5-10 min). Patients prone to lowering blood pressure, such as hypovolemia, atracurium bezylate it is recommended to enter for at least 60 seconds.

Atracurium bezylate is inactivated in an alkaline medium and should not be mixed in one syringe with sodium thiopental or alkaline solutions.

If a peripheral vein of small caliber is used to inject a solution of atrakury bezilate, then after injection, it should be washed with 0.9% sodium chloride solution.

A solution of atracurium bezylate is hypotonic and should not be used simultaneously through a single system with blood transfusions.

Atracuria bezylate does not cause malignant hyperthermia.

In patients with burns, resistance to non-depolarizing muscle relaxants may develop, which requires an increase in the doses of these drugs, the magnitude of which depends on the time that has passed after the burn and on the area of its surface.

Effect on the ability to drive transp. cf. and fur:Patients who received the drug should refrain from potentially dangerous activities associated with the need for concentration and increased speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous administration 10 mg / ml.

Packaging:

For 2.5 ml of the drug in a colorless glass ampoule, hydrolytic class I, with a vestigial and white point or without a dot on the top of the ampoule. 5 ampoules (in a pallet of PVC), along with instructions for use, are placed in a cardboard box with the stickers of the first opening.

For 5 ml of the drug in a colorless glass ampoule, hydrolytic class 1, with a vestigial and white point or without a dot on the top of the ampoule. 5 ampoules (in a pallet of PVC), along with instructions for use, are placed in a cardboard box with the stickers of the first opening.

Storage conditions:

Store at a temperature of 2 to 8 ° C.

Do not freeze.

The solution of atracurium besylate, which is not used after opening the ampoule, must be destroyed.

Keep out of the reach of children.

Shelf life:

2 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001800

Date of registration:14.08.2012

The owner of the registration certificate:Fri. Novell Pharmaceutical LaboratoriesFri. Novell Pharmaceutical Laboratories Indonesia

Manufacturer: & nbsp

PT. NOVELL PHARMACEUTICAL LABORATORIES Indonesia

Representation: & nbspSVYCH LLC SVYCH LLC Russia

Information update date: & nbsp19.02.2014

Illustrated instructions

Instructions

Notrixum (Notrixum)