Trakrium

General characteristics. Structure:

Solution for in/in introductions transparent, from colourless till light yellow color.

Active ingredient: atrakuriya безилат 10 mg 25 mg

Excipients: solution of benzenesulphonic acid of 32%, water for and.

2.5 ml - ampoules with a ceramic spot of blue color and two color rings on an upper part of ampoules

Solution for in/in introductions transparent, from colourless till light yellow color.

Active ingredient: atrakuriya безилат 10 mg 50 mg

Excipients: solution of benzenesulphonic acid of 32%, water for and.

Pharmacological properties:

Muscle relaxant of peripheral action of not depolarizing competitive type. Atrakuriya безилат reduces sensitivity of N-holinoretseptorov of synoptic area to acetylcholine owing to what there is impossible an excitement of muscle fiber and its reduction. Promotes release of a histamine.

Atrakuriya безилат does not exert a direct impact on intraocular pressure. Thus, an atrakuriya безилат it is applicable in ophthalmologic surgical practice.

 

Pharmacokinetics. Metabolism

Atrakuriya безилат is inactivated by means of Hoffmann's elimination (process which happens at physiological values рН and temperatures without participation of enzymes) and by radio hydrolysis with the participation of nonspecific esterases. Plasma researches at patients with the low level of pseudo-cholinesterase showed that metabolism products an atrakuriya of a bezilat do not change.

Changes of values рН blood and body temperatures in physiological limits slightly influence action duration an atrakuriya of a bezilat.

Removal

Duration of the neuromuscular blockade caused by introduction an atrakuriya of a bezilat does not depend on his metabolism in a liver or kidneys, or on its excretion. Therefore it is improbable that duration of effect of drug changes at disturbances of functions of kidneys, a liver or disturbances of blood circulation.

Pharmacokinetics in special clinical cases

Haemo filtering and hemodiafiltration exert the minimum impact on concentration an atrakuriya of a bezilat and its metabolites (including laudanosine) in a blood plasma. Influence of a hemodialysis and hemoperfusion on concentration an atrakuriya of a bezilat and its metabolites in a blood plasma is unknown.

At patients of the block of an intensive care (BIC) with renal failures and/or a liver higher concentration of metabolites an atrakuriya of a bezilat were observed. Metabolites do not exert impact on neuromuscular conductivity.

Indications to use:

— as a component of the general anesthesia for ensuring carrying out an intubation of a trachea and relaxation of skeletal muscles at surgical interventions, or the managed ventilation of the lungs, and for simplification of carrying out the artificial ventilation of the lungs (AVL) at patients in the block of an intensive care (BIC).

Route of administration and doses:

Тракриум® enter in/in in the form of injections. For adults the range of doses makes 300-600 mkg/kg (depending on the necessary duration of a total block) that provides an adequate mioplegiya within 15-35 min.

Later in doses of 500-600 mg/kg the endotracheal intubation can be carried out to introductions, as a rule, after 90 sec.

In need of prolongation of total neuromuscular block in addition enter Trakrium® in a dose of 100-200 mkg/kg. The correct introduction of additional doses of drug does not lead to cumulation of myorelaxation effect.

Spontaneous recovery of conductivity after total neuromuscular block happens approximately in 35 min. that is determined by recovery of tetanic reduction to 95% of normal neuromuscular function. The neuromuscular blockade caused atrakuriy can be quickly eliminated by use of antikholinesterazny means in standard doses, such as неостигмин and edrofoniya, in combination with simultaneous or preliminary administration of atropine (without emergence of signs of a rekurarization).

After an initial bolyusny dose of 300-600 mg/kg of Trakrium® it is possible to apply to maintenance of neuromuscular blockade during long surgical intervention by long infusion with a speed of 300-600 mkg/kg/h of Trakrium® it is possible to enter by infusion during operation of kardiopulmonarny shunting with the speed recommended for infusion. At the induced hypothermia with body temperature from 25 ° to 26 °C the speed of an inactivation of Trakrium decreases, thus, for maintenance of full muscle relaxation at low temperatures the speed of infusion is reduced approximately twice.

To children at the age of 2 years Trakrium® is also more senior appoint in the same doses, as well as the adult, in terms of body weight.

The initial dose of Trakrium applied at children aged from 1 month up to 2 years at galotanovy anesthesia makes 300-400 mg/kg. At children more frequent use of maintenance doses, than at adults can be required.

Тракриум® it is possible to apply in standard doses at patients of advanced age. However it is recommended to apply an initial dose which less lower value of range of doses, and to administer the drug slowly.

Тракриум® it is possible to apply in standard doses at any degree of an abnormal liver function or kidneys, including insufficiency of a final stage.

At patients with cardiovascular diseases with the expressed symptoms the initial dose of Trakrium should be entered during 60 sec.

Use for patients of BITS

After introduction in case of need Trakrium in an initial bolyusny dose of 300-600 mg/kg it is possible to use drug for maintenance of neuromuscular blockade by performing long infusion with a speed of 11-13 mkg/kg/min. (650-780 mkg/kg/h). However there are wide interindividual distinctions in the dosing mode. The mode of dosing can change in time. At some patients can be required as the low speed of infusion - 4.5 mkg/kg/min. (0.27 mg/kg/h), and high - 29.5 mkg/kg/min. (1.77 mg/kg/h).

Speed of spontaneous recovery after neuromuscular blockade at the end of infusion of Trakrium at patients of BITS does not depend on introduction duration. Spontaneous recovery of neuromuscular conductivity (a ratio of height of a quarter to the first twitching in the train-of-four T4/T1 test> 0.75) usually happens approximately in 60 min. In clinical trials this period made from 32 to 108 min. after Trakrium's infusion, and his speed does not depend on duration of administration of drug.

Monitoring

As well as at use of other muscle relaxants, during the entire period of use of Trakrium monitoring of neuromuscular function for definition of the mode of dosing in each separate case is recommended.

Features of use:

As well as other muscle relaxants, Trakrium® are caused by paralysis of skeletal muscles, including respiratory muscles, but does not influence consciousness.

Тракриум® it is necessary to enter only into time of the general anesthesia under careful observation of the qualified anesthesiologist in the presence of the equipment for carrying out an intubation of a trachea and IVL.

At use in the recommended range of doses of Trakrium® does not cause significant blockade of a vagus nerve and nervous ганглиев. Therefore, Trakrium® in the recommended range of doses does not make clinically significant impact on ChSS and does not prevent the bradycardia caused by anesthetics or stimulation of a vagus nerve during operation.

Patients with tendency to sharp decrease in the ABP, for example, with a hypovolemia, Trakrium® are recommended to enter during more than 60 sec.

Тракриум® it is inactivated in the alkaline environment, and it should not be mixed in one syringe with Tiopentonum or any alkaline solutions.

If Trakrium's introduction is made in a vein of small caliber, then after an injection it should be washed out normal saline solution. At administration of other anesthetics through the same syringe needle or a cannula important that each drug was washed away by the corresponding quantity of normal saline solution.

Trakrium's solution hypotonic, and it cannot be entered at the same time through one system with a hemotransfusion.

Clinical trials at the patients sensitive to a malignant hyperthermia, show that Trakrium® does not cause this syndrome.

At patients with burns resistance to not depolarizing muscle relaxants can develop. In such cases increase in doses which size depends on time which passed after a burn and on burn surface area can be required.

At patients of the BITS receiving Trakrium® spasms were noted, however, the causal relationship of their development (a metabolite an atrakuriya of a bezilat) is not established with laudanosine.

Influence on ability to driving of motor transport and to control of mechanisms

Data are absent.

Side effects:

The side reactions classified by systems of bodies and frequency are listed below. Frequency of side reactions is determined as follows: very often (≥1/10), it is frequent (≥1/100 and <1/10), sometimes (≥1/1000 and <1/100), is rare (≥1/10 000 and less than 1/1000), is very rare (<1/10 000) and separate messages (in case data for determination of frequency of emergence of side reaction are not enough).

Data of clinical trials

From cardiovascular system: often - passing decrease in the ABP, a dermahemia.

From respiratory system: sometimes - a bronchospasm.

These undesirable phenomena are connected with emission of a histamine.

Post-marketing data

From immune system: very seldom - anaphylactic and anaphylactoid reactions. It was very seldom reported about heavy anaphylactic or anaphylactoid reactions at the combined use of Trakrium with anesthetics.

From a nervous system: in some cases - spasms. The patients who are on an intensive care, receiving had messages on cases of developing of spasms and other drugs, except Trakrium. Usually these patients had premises for developing of spasms, such as head injury, brain hypostasis, viral encephalitis, hypoxemic encephalopathy, uraemia. Communication between developing of attacks and use of laudanosine is not established. As a result of clinical trials correlation between plasma concentration of laudanosine and developing of attacks is absent.

From a musculoskeletal system: in some cases - a myopathy, muscular weakness. It was reported about several cases of a myopathy and/or muscular weakness at long use of muscle relaxants at seriously ill patients of the patients who are in the block of an intensive care. Most of them at the same time received GKS. This side reaction is regarded as uncharacteristic for Trakrium, connection using drug is not established.

Interaction with other medicines:

The neuromuscular blockade induced by Trakrium can amplify at use of means for an inhalation anesthesia, such as halothane, изофлуран, энфлуран.

As well as at use of other not depolarizing muscle relaxants, increase in intensity and/or duration of neuromuscular blockade as a result of interaction with the following drugs is possible: antibiotics (aminoglycosides, polymyxins, спектиномицин, tetracyclines, lincomycin and clindamycin); antiarrhytmic means (propranolol, blockers of calcium channels, lidocaine, procaineamide and quinidine); diuretics (furosemide and, perhaps, Mannitolum, thiazide diuretics and acetazoleamide); magnesium sulfate; Ketaminum; lithium salts; ganglioblokator (триметафан, geksametoniya).

In rare instances certain drugs cause a myasthenia aggravation, promote development of a myasthenia from a latent form, and also a myasthenic syndrome at which increase in sensitivity to Trakrium is possible. Various antibiotics, beta adrenoblockers (propranolol, Oxprenololum), antiarrhytmic (procaineamide, quinidine) and antirheumatic drugs (chloroquine, D-Penicillaminum), триметафан, Chlorpromazinum, steroids, Phenytoinum and salts of lithium belong to such drugs.

Development of the neuromuscular blockade caused by not depolarizing muscle relaxants probably is slowed down, and its duration decreases at the patients receiving anticonvulsant therapy for a long time.

The combined use of not depolarizing blockers of neuromuscular conductivity and Trakrium can cause excessive blockade, in comparison with expected from one Trakrium's introduction in an equipotential total dose. Any effect caused by a synergism can change at various combinations of drugs.

The chloride depolarizing a succinylcholine muscle relaxant should not be applied to prolongation of the neuromuscular blockade caused by not depolarizing muscle relaxants, such as Trakrium® as it can cause the prolonged and difficult blockade which is difficult for stopping antikholinesterazny means.

Therapy by the antikholinesterazny drugs which are often used for treatment of Alzheimer's disease, for example, donepezil can shorten duration of neuromuscular blockade and weaken the blocking Trakrium's effect.

Pharmaceutical compatibility

Тракриум® it is compatible to the following infusion solutions during the specified time:

Infusion solution                                  stability Period

Chloride sodium solution for infusion of 0.9%            of 24 h
Glucose solution for infusion of 5%                           of 8 h
Ringer's solution for injections                                of 8 h
Solution of sodium of chloride of 0.18% and
glucose of 4% for infusion                                         of 8 h
Lactate sodium solution difficult for
infusions (Hartman's solution for injections)              4 h

Trakrium's solution at cultivation by compatible infusion solutions before obtaining concentration the atrakuriya of a bezilat of 500 mkg/ml also more keeps stability at day lighting during the determined period at a temperature up to 30 °C.

Contraindications:

— the known hypersensitivity to an atrakuriya, a tsisatrakuriya or to benzenesulphonic acid, any other components of drug;

— the known hypersensitivity to a histamine.

Can cause development of the reactions connected with release of a histamine in predisposed patients of Trakrium®. It is necessary to be careful at Trakrium's introduction to patients with instructions in the anamnesis on hypersensitivity to effects of a histamine.

Care is also required at Trakrium's introduction to patients at whom hypersensitivity reactions to other muscle relaxants since the high frequency of occurrence of cross sensitivity between muscle relaxants (more than 50%) is revealed were observed.

As well as at use of other not depolarizing muscle relaxants, hypersensitivity to Trakrium can be observed at patients with a heavy myasthenia, other neuromuscular diseases and heavy disturbances of electrolytic balance.

 

Use of the drug TRAKRIUM® at pregnancy and feeding by a breast

Studying of influence on fertility was not carried out.

Тракриум® it is necessary to apply at pregnancy only in cases when the potential advantage for mother exceeds any possible risk for a fruit.

Тракриум® it is possible to apply for the purpose of muscle relaxation at operation of Cesarean section since at appointment in the recommended doses the atrakuriya безилат gets through a placental barrier in clinically insignificant quantities.

It is unknown whether the atrakuriya безилат with breast milk at the person is allocated.

 

Use at abnormal liver functions

Тракриум® it is possible to apply in standard doses at any degree of an abnormal liver function, including insufficiency of a final stage.

 

Use at renal failures

Тракриум® it is possible to apply in standard doses at any degree of a renal failure, including insufficiency of a final stage.

 

Use for elderly patients

Тракриум® it is possible to apply in standard doses at patients of advanced age. However it is recommended to apply an initial dose which less lower value of range of doses, and to administer the drug slowly.

 

Use for children

To children at the age of 2 years Trakrium® is also more senior appoint in the same doses, as well as the adult, in terms of body weight.

The initial dose of Trakrium applied at children aged from 1 month up to 2 years at galotanovy anesthesia makes 300-400 mg/kg. At children more frequent use of maintenance doses, than at adults can be required.

Overdose:

Symptoms: the prolonged muscular paralysis and its effects are the main symptoms of overdose.

Treatment: the major is maintenance of passability of respiratory tracts along with carrying out IVL under positive pressure before recovery of adequate spontaneous breath. Use of sedative drugs as consciousness of patients is not broken is necessary. As soon as there are signs of spontaneous recovery, it can be accelerated by means of antikholinesterazny drugs in combination with atropine or glycopyrrolate.

Storage conditions:

It is necessary to store drug in protected from light, the place, unavailable to children, at a temperature from 2 ° to 8 °C; not to freeze. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

• solution for in/in introductions of 25 mg / 2.5 ml: amp. 5.

• solution for in/in introductions of 50 mg / 5 ml: amp. 5.