Tracrium® (Tracrium®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceAtracuria bezylateAtracuria bezylate
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    • Dosage form: & nbspsolution for intravenous administration
    Composition:

    Composition per ml:

    Name of components

    amount

    Active substance

    Atracuria bezylate1

    10.0 mg


    Excipients

    Acids, benzenesulfonic solution 32% (w / v)

    q.s. to pH

    3,0-3,8

    Water for injections

    up to 1.0 ml

    Notes: 1. A 10% excess of atracurium bezylate is used, but this is not reflected in the above figures.

    Description:Transparent solution from colorless to light yellow color.
    Pharmacotherapeutic group:Nondepolarizing muscle relaxant of peripheral action.
    ATX: & nbsp

    M.03.A.C   Other quaternary ammonium compounds

    M.03.A.C.04   Atracuria bezylate

    Pharmacodynamics:

    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 metabolic products of atracurium bezylate 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. The influence of hemodialysis and hemoperfusion on the concentration of atracurium besylate and its metabolites in blood plasma is unknown.

    In patients with the intensive care unit (BIT) with impaired renal and / or liver function, higher concentrations of atra- kury besylate metabolites were observed, Metabolites had no effect on neuromuscular conduction.

    Indications:

    - as a component of general anesthesia to ensure intubation of the trachea and relaxation of skeletal muscles in surgical procedures or controlled ventilation of the lungs and to facilitate artificial ventilation in patients in the Intensive Care Unit (BIT).

    Contraindications:

    - known hypersensitivity to atracuria, cisatracuria benzylsulfonic acid, any other components of the drug.

    - Known hypersensitivity to histamine

    Carefully:
    Pregnancy and lactation:

    Fertility

    The effect on fertility has not been studied.

    Pregnancy

    Animal studies have shown that the use of Tracrium® does not have a significant effect on fetal development. Like other muscle relaxants, Tracryum® should be used during pregnancy only if the potential benefit to the mother exceeds any possible risk to the fetus.

    Trekrium ® can be used for the purpose of muscle relaxation during a caesarean section, since when prescribed in recommended doses, Tracium® does not penetrate the placental barrier in clinically significant amounts. Breastfeeding period It is not known whether Tracium® is excreted in breast milk.

    Dosing and Administration:

    The table of pharmaceutical compatibility of Tracium with some infusion solutions is given in the section "Interaction with other drugs and other interactions".

    Patient groups

    - Injectable use in adults

    Tracium injected intravenously. For adults, the dose range is about,3-0.6 mg / kg (depending on the required duration of complete blockade), which provides adequate myoplegia within 15-35 minutes.

    After intravenous administration in doses of 0.5-0.6 mg / kg, endotracheal intubation can be carried out, as a rule, after a lapse of 90 seconds.

    If it is necessary to prolong the complete neuromuscular blockade, Tracrium is 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, Tracium can be used to maintain neuromuscular blockade during prolonged surgical intervention by prolonged infusion at a rate of 0.3-0.6 mg / kg / h.

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

    Children

    Children aged 2 years and older are prescribed Tracium in the same doses as adults, in terms of body weight.

    The initial dose of Tracium 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

    Tracium 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.

    Use in patients with impaired renal and / or liver function.

    Trakrium can be used in standard doses for any degree of impaired liver or kidney function, including end-stage insufficiency.

    Use in patients with cardiovascular disease

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

    The use of BIT in patients

    After the administration of Tracrium in the initial bolus dose of 0.3-0.6 mg / kg, if necessary, the drug can be used to maintain neuromuscular blockade by performing a continuous 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 / h).

    The rate of spontaneous recovery after neuromuscular blockade at the end of Tracium infusion in BIT 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/Ti>0,75) usually occurs in about 60 minutes. In clinical trials, this period ranged from 32 to 108 min after Tracium infusion, and its rate does not depend on the duration of administration of the drug.

    Monitoring

    As with the use of other muscle relaxants, it is recommended that during the entire period of Tracium use, a neuromuscular function is monitored to determine the dosage regimen in each individual case.

    Side effects:

    The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1 000 and <1/100), rarely (> 1/10 000 and <1/1 000), very rarely (<1/10 000). Frequency categories very often, often and infrequently, were formed on the basis of clinical studies of the drug. Categories of frequency are rare, very rarely were formed on the basis of spontaneous messages. The category is unknown to those reactions whose frequency can not be established based on available data.

    Clinical Trials Data

    Vascular disorders

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

    Disturbances from the respiratory system, chest and mediastinal organs

    Infrequent: bronchospasm#.

    Undesirable reactions associated with the release of histamine are indicated by the sign #.

    Post-registration data

    Immune system disorders

    Very rarely: anaphylactic reactions and anaphylactoid reactions, including shock, circulatory failure and cardiac arrest. Very rarely reported severe anaphylactoid or anaphylactic 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 BIT 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 studies, there is no correlation between plasma concentrations of laudanosine and the occurrence of seizures.

    Disturbances from the skin and subcutaneous tissues

    Rarely: urticaria.

    Disturbances from musculoskeletal and connective tissue

    Unknown: myopathy, muscle weakness.Several cases of muscle weakness and / or myopathy have been reported with prolonged use of muscle relaxants in critically ill patients in BIT. 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 muscle paralysis and its consequences are the main symptoms of an overdose.

    Treatment

    The most important is the maintenance of airway patency simultaneously with the ventilation under positive pressure to restore adequate spontaneous breathing.

    It is necessary to use sedatives, because the consciousness of patients is not violated.

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

    Interaction:

    Trumentum-induced neuromuscular blockade may be exacerbated by the use of inhalation anesthetics 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, which may increase the sensitivity to Tracry. These drugs include various antibiotics, beta-blockers (propranolol, oxprenolol), antiarrhythmic (procainamide, quinidine) and antirheumatic drugs (chloroquine, D-penicillamine), 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 Tracium may cause an excessive blockade compared to the one expected from the introduction of a single Tracium in an equipotential total dose. Any effect due to synergism can change with different combinations of drugs.

    Depolarizing muscle relaxant suxamethonium chloride should not be used to prolong neuromuscular blockade caused by nondepolarizing muscle relaxants, such as Tracium, as this can cause a prolonged and difficult 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 the neuromuscular blockade and weaken the blocking effect of Tracium.

    Pharmaceutical compatibility

    Trakrium is compatible with the following infusion solutions for the specified time:

    Infusion solution Stability period

    A solution of sodium chloride 24 h

    for infusions 0,9% (VR)

    Glucose solution for 8 h

    infusions 5% (VR)

    Ringer's solution for 8 h

    injections (USP)

    A solution of sodium chloride 8 h

    0.18% and glucose 4% for

    infusions (VR)

    A solution of sodium lactate 4 hours

    difficult for infusions (VR)

    (Hartmann Solution for Injection)

    Tracium solution when diluted with compatible infusion solutions to obtain a concentration of atrachium besylate 0.5 mg / ml or more preserves stability under daylight for a specified period at temperatures up to 30 ° C.
    Special instructions:

    Like other muscle relaxants, a drug Tracium® causes paralysis of the respiratory muscles, as well as skeletal muscles, but does not affect consciousness. A drug Trakrium® should only be entered from general anesthesia under the careful supervision of a qualified anesthesiologist with the availability of equipment for intubation of the trachea and mechanical ventilation.

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

    Caution is also required when administering Tracrium® patients who have experienced hypersensitivity reactions to other muscle relaxants, t. a high frequency of cross-sensitivity between muscle relaxants (more than 50%) was detected (see Contraindications).

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

    When used in the recommended dose range a drug Tracium® does not cause a significant blockage of the vagus nerve and nerve ganglia. Consequently, a drug Tracium® in the recommended dose range does not have a clinically significant effect on heart rate and does not prevent bradycardia caused by by many anesthetics or stimulation vagus nerve during the operation.

    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 Tracrium®.

    As with other non-depolarizing muscle relaxants, increased sensitivity to Tracrium® can 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, a drug Tracium® is recommended for more than 60 seconds.

    A drug Trakrium® is inactivated in an alkaline environment, and its can not mix in one syringe with thiopental or any alkaline solutions.

    If the introduction preparation Trakrium® is produced in a vein of small caliber, then after injection it should be washed with physiological solution.When other anesthetics are injected through the same injection needle or cannula, it is important that each drug is washed off with an appropriate amount physiological solution.

    Solution preparation Tracrium® hypotonic, and it can not be administered simultaneously through a single system with blood transfusion.

    Research malignant hyperthermia the predisposing animals (pigs) and clinical studies in patients, sensitive to malignant hyperthermia, show that a drug Tracium® does not cause this syndrome.

    As with other non-depolarizing muscle relaxants, the patients with burns with administration of Tracrium® may develop resistance. 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 at BIT: introduction of laboratory animals in large doses of laudanosine, the metabolite of atracurium bezylate, was associated with a transient decrease in blood pressure, and in some species of animals with cerebral stimulatory effects. Patients at BIT, who received a drug Tracry®, there were convulsions, however, the cause- investigatory the relationship of their development with laudanosine (metabolite of atracurium bezylate) not installed (see Adverse Effect).

    Effect on the ability to drive transp. cf. and fur:This indication is unacceptable when using Tracrium®, because it is always used only for general anesthesia.

    Form release / dosage:Solution for intravenous administration 10 mg / ml.
    Packaging:5 ampoules of neutral glass type I with a blue ceramic spot and two colored rings on the top of the ampoules containing 2.5 ml or 5.0 ml of a 10 mg / ml solution for intravenous administration of atracurium bezylate are placed in a plastic tray. The plastic pallet along with the instruction for use is placed in a cardboard box.
    Storage conditions:

    At a temperature of 2-8 0C in a dark place out of the reach of children.

    Do not freeze.

    Shelf life:

    2 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:П N015100 / 01
    Date of registration:13.10.2008
    The owner of the registration certificate:GlaxoSmithKline group of companies GlaxoSmithKline group of companies Unknown
    Manufacturer: & nbsp
    Representation: & nbspGlaxoSmithKline group of companies GlaxoSmithKline group of companies Unknown
    Information update date: & nbsp28.11.2014
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