PRODUCT

Active material: Tsisatrakuriya besilate
When ATH: M03AC11
CCF: Muscle relaxants peripherally acting non-depolarizing competitive type
ICD-10 codes (testimony): Z51.4
When CSF: 21.03.01.01
Manufacturer: GlaxoSmithKline s. p. a.. (Italy)

Pharmaceutical form, composition and packaging

The solution for the on / in the clear, from colorless to pale yellow or greenish-yellow, free from visible mechanical inclusions.

Excipients: r-r benzolsul′fonovoj acid 32%, water d / and.

2.5 ml – ampoule (5) – packs cardboard.

The solution for the on / in the clear, from colorless to pale yellow or greenish-yellow, free from visible mechanical inclusions.

Excipients: r-r benzolsul′fonovoj acid 32%, water d / and.

5 ml – ampoule (5) – packs cardboard.

The solution for the on / in the clear, from colorless to pale yellow or greenish-yellow, free from visible mechanical inclusions.

Excipients: r-r benzolsul′fonovoj acid 32%, water d / and.

10 ml – ampoule (5) – packs cardboard.

Pharmacological action

Non-depolarizing muscle relaxant average duration, It is a derivative of gasilishinolin.

Cisatrakuria Bezilat is associated with H-cholinoreceptors of the end of the motor nerves and acts as an antagonist acetylcholine, causing competitive blockade of neuromuscular conduction, which can be rapidly eliminated by anticholinestural agents such.

When used in doses, in 8 times the ED₉₅ (the average dose, necessary for 95% suppressing the reaction of the removal muscle of the thumb in response to stimulation of the elbow nerve), Nahbeks^® does not cause dose -dependent release of histamine.

ED₉₅ Cisatrakuria Bezilates during opioid anesthesia (Thiopental/Fentanyl/Midazolam) is 50 mg / kg.

ED₉₅ Cisatrakuria of Bezilates in children during halotane anesthesia is equal 40 mg / kg.

Pharmacokinetics

When using the drug in a dose to 400 mcg/kg The pharmacokinetic parameters of Cisatrakuria of Bezilates do not depend on the dose (8×ED₉₅).

Metabolism

Cisatrakuria bezilate is metabolized in the body with physiological values of pH and temperature by elimination of Hofmann (Chemical process) with the formation of laudanosine and monochetic acrylate metabolite. The latter is hydrolyzed under the influence of non -specific asterazes of plasma with the formation of monochetic alcohol. Metabolites do not have a muscle relaxing activity.

Pharmacokinetic parameters of nimbeks^® in doses more 100 mg / kg 200 mcg/kg in adult surgical patients are presented in the table.

The average clearance of Cisatrakuria of Bezilata is 6.9 ml / kg / min, a T_1/2 – 28 m. The removal of the drug does not depend on the duration of infusion, Metabolites are excreted by kidneys and liver.

Pharmacokinetic parameters of Cisatrakuria of Bezilat after the introduction^® In the form of infusion or bolus are similar.

Pharmacokinetics in special clinical situations

The clinically significant difference in the pharmacokinetics of Cisatrakuria Bezilate in young and elderly people does not, Its plasma clearance does not change depending on age. However, there is a slight increase_d (+17%) and T_1/2 (+4 m) elderly patients.

The clinically significant difference in the pharmacokinetics of Cisatrakuria of Bezilates in patients with the final stage of renal failure and in healthy volunteers is not observed. The removal of the drug is also not violated with renal failure.

The clinically significant difference in the pharmacokinetics of Cisatrakuria Bezilates with liver failure and healthy volunteers do not have. However, with hepatic deficiency, there is a slight difference in size V_d (+21%) and clearance (+16%) tile, but t_1/2 and the excretion of the drug does not change.

Pharmacokinetics of Cisatracuria of Bezilata in patients in OIT, receiving it in the form of prolonged infusion, does not differ from such with a single -sized introduction. The average clearance of Cisatrakuria of Bezilata is 7.5 ml/kg/min and t_1/2 is equal to 27 m. The removal of the drug after prolonged infusion administration does not depend on the duration of the infusion. The concentration of metabolites is higher in those patients in Oit, in which the function of the kidneys and/or liver is impaired. However, these metabolites do not affect the neuromuscular blockade.

Testimony

- to maintain myoplegia and conduct the intubation of the trachea and Ivl during surgical operations;

- for IVL in intensive care units.

Dosage regimen

In Adult at intubation Recommended dose of nimbeks^® For bolus administration is 150 mg / kg, which is quickly introduced during 5-10 sec and provides optimal conditions for the intubation of the trachea through 120 sec after injection.

When the drug is introduced in higher doses, the neuromuscular blockade occurs faster. The table shows the average pharmacodynamic indicators of nimbeks^® when introduced in doses from 100 to 400 ICG/kg healthy adult volunteers during anesthesia opioids (Thiopental sodium/fentanyl/midazolam) or propofolom.

T1^and – Single reduction, as well as the first component of the reaction of the muscle, thumb gives the thumb, on supramaximal electrical stimulation of the elbow nerve.

Enfluran or Isofluran can lengthen the duration of the blockade, caused by the initial dose of nimbeks^®, on 15%.

The duration of the neuromuscular blockade can be increased by supporting doses Napex^®. During anesthesia by opioids or propotel Nimbeks^® dose 30 mcg/kg lengthens the neuromuscular blockade approximately by 20 m. However, the subsequent introduction of supporting doses does not lead to its progressive elongation.

After, as spontaneous restoration of neuromuscular conduction It began, Its speed does not depend on the introduced dose of nimbeks^®. During anesthesia by opioids or halotan, the average recovery time with conductivity with 25% to 75% and 5% to 95% approximately 13 Mines and 30 min, respectively.

Caused by a nibeks^® The neuromuscular blockade is easy eliminated under the action of anticholinsterase means at standard doses. Average conduct of conductivity with 25% to 75% and its complete restoration (coefficient t₄:T₁≥0.7) after the introduction of an anticholinsterase drug on average at 13% T₁ conductivity restoration is approximately 2 Mines and 5 min, respectively.

In children aged 1 Months before 12 years at intubation starting dose is 150 mg / kg, The drug is administered quickly in/to during 5-10 sec, which creates optimal conditions for the intubation of the trachea during 120 sec after injection. To ensure neuromuscular blockade, the initial dose of nimbeks is recommended^® 100 mg / kg; In this case, the optimal conditions for the intubation of the trachea are created on 120-150 sec after the drug. When using a nibex^® in children aged 1 Months before 12 years the duration of neuromuscular blockade decreases, And its spontaneous recovery occurs faster compared to adults with the same anesthesia. Minor differences in the pharmacodynamic indicators of nibex are revealed^® in children 1-11 months from those in children aged 1-12 years.

Pharmacodynamic indicators of Nimbeks^® to children 1-11 Months are presented in Table.

Pharmacodynamic indicators of Nimbeks^® to children 1-12 years

Galotan can increase the duration of the neuromuscular blockade, Caused by a nimbeks^®, a maximum of 20%. Information about the use of nimbeks^® In children during anesthesia, isofluran or Enfluran, However, you can expect, that these inhalation anesthetics are also able to increase the duration of the neuromuscular blockade, Caused by a nimbeks^®, a maximum of 20%.

The duration of the neuromuscular blockade can be increased by introducing nibeks^® in supporting doses. With anesthesia with a halotan, the introduction of nimbeks^® dose 20 ICG/kg increases the duration of the neuromuscular blockade by approximately 9 m. The subsequent introduction of supporting doses does not lead to its progressive elongation.

After, as spontaneous restoration of neuromuscular conduction It began, Its speed does not depend on the introduced dose of nimbeks^®. During anesthesia by opioids or halotan, the average recovery time with conductivity with 25% to 75% and 5% to 95% approximately 11 Mines and 28 min, respectively.

Caused by a nibeks^® The neuromuscular blockade is easy eliminated under the action of anticholinsterase means at standard doses. Average conduct of conductivity with 25% to 75% and its complete restoration (coefficient t₄:T₁≥0.7) after the introduction of an anticholinsterase drug on average at 13% T₁ conductivity restoration is approximately 2 Mines and 5 min, respectively.

Adults and children aged 1 Months before 12 years to maintaining neuromuscular blockade Nahbeks^® can be administered by infusion. For stabilization t₁-Conductivity blockade at the level 89-99% After the appearance of signs of its spontaneous recovery, the initial infusion rate is recommended 3 ug / kg / min (180 mcg/kg/h). After stabilization of the neuromuscular blockade to maintain it at this level in most patients, the infusion rate within the range is sufficient 1-2 ug / kg / min (0.06-0.12 mg / kg / hr). During anesthesia, isofluran or enfluran, a decrease in the velocity of nihbeks infusion may be required^® on 40%. The infusion rate depends on the concentration of cisatracuria of a bezilate in an infusion solution, from the required depth of neuromuscular blockade and body weight of the patient. The table contains recommendations on the speed of infusion administration of undiluted niibex solution^® Injectable.

Continuous infusion of Nimbeks^® With constant speed, it is not accompanied by progressive increased or weakening of the neuromuscular blockade. After the cessation of Nimbex infusion^® spontaneous restoration of neuromuscular conduction occurs at speed, comparable to that after a single -sized administration of the drug.

Despite, that the introduction of Nimbeks^® In the form of infusion, it was not specifically studied in children aged 2 years, By analogy with doses for bolus administration, one can assume, that the infusion rate in this age group should be the same, Like older children.

No data on the use of nimbeks^® in children aged 1 Months, Therefore, it is impossible to give recommendations for dosing the drug in this age group.

Dose adjustment at elderly patients not required. Pharmacodynamics nimbeks^® They have similar to that in young patients, However, the action of the nibex^® (Like other muscle relaxants) can begin a little later.

Dose adjustment at patients with renal insufficiency not required. Pharmacodynamics nimbeks^® They have similar to that in patients with normal kidney function, However, the action of the nibex^® can begin a little later.

Dose correction patients with the terminal stage of liver failure not required. Pharmacodynamics nimbeks^® They have similar to that in patients with a normal liver function, However, the action of the nibex^® can begin a little earlier.

Nahbeks^® Successfully used as a muscle relaxant for heart surgery. The quick introduction of Nimbeks^® (during 5-10 sec) in the form of a bolus in any studied dose (to 400 MKG/kg inclusive) Patients with severe cardiovascular diseases are not accompanied by clinically significant reactions from the cardiovascular system.

Adults patients, located in Oit, Nahbeks^® can be introduced in/in jet and/or drip.

For adult patients, the recommended initial velocity of nibex infusion^® is 3 ug / kg / min (180 mcg/kg/h). The required dose varies widely in different patients and may increase or decrease over time. In clinical studies, the average infusion rate was 3 ug / kg / min (from 0.5 to 10.2 MCG/kg/min/from 30 to 600 mkg / kg / ().

The average time to complete spontaneous restoration of conductivity after a long (to 6 days) Nimbeks infusion^® In patients in OIT, it is approximately 50 m.

Restoration of conductivity after Nimbeks infusion^® In patients in OIT, it does not depend on the duration of infusion.

No data on the use of nimbeks^® during heart operations in conditions of hypothermia (from 25 ° to 28 ° C). Necessary for maintaining adequate muscle relaxation under these conditions, the infusion rate of nimbeks^® can be significantly lower (As when using other muscle relaxants).

Cooking rules, use and storage of solution

Divorced solution of nimbeks^® for injection stable during 24 h at a temperature of 5-25 ° C in concentrations from 1 to 2 mg/ml in the following liquids for ivation (in containers made of polyvinyl chloride or polypropylene): 0.9% sodium chloride solution for iv infusion; 5% DECSROSE solution for iv infusion.

Since the drug does not contain antimicrobial preservatives, its breeding should be carried out immediately before the use. The prepared solution must be immediately introduced, and its remnants should be poured.

Nahbeks^® chemically unstable when breeding in a solution of Ringer. When the introduction of other drugs through the same needle or cannula, through which Nimbeks was introduced^®, It is recommended to rinse the needle and cannula with a sufficient amount of compatible solution for iv administration (eg, physiological solution) After the administration of each drug. Nahbeks^® stable only in acidic solutions, Therefore, it should not be mixed in one syringe or administer simultaneously through one needle with alkaline solutions (eg, With sodium thiopental).

If for the injection of nimbeks^® The peripheral vein of small caliber is used, It should be washed after the administration of the drug with a compatible solution for iv administration (eg, physiological solution).

Side effect

The frequency of adverse reactions, possibly associated with the introduction of nibeks^®, is less than 0.5%.

Allergic reactions: erythema, rash, bradycardia, hypotension, bronchospasm; rarely – Severe anaphylactic reactions in patients, receiving Nimbeks^® In combination with one or more anesthetics.

Other: There are separate reports on the development of muscle weakness and/or myopathy after prolonged use of muscle relaxants in seriously ill patients in OT. Most of these patients received corticosteroids. Similar phenomena are rarely observed with the use of nibex^®; Most of them have not established a relationship using cisatrakuria of the Besilate.

Contraindications

- increased sensitivity to cisatrakuria to Besilate, Atrakuria to Bezilat, Benzolsulfonic acid.

FROM caution used in violation of acid-base equilibrium and electrolyte balance, carcinomatosis, neuromuscular diseases (incl. myasthenia gravis and myasthenic syndrome) or other conditions, which can lead to long-term neuromuscular blockade; burns; Hemereypeese or Paraparezsee.

Pregnancy and lactation

The drug does not have an undesirable effect on the development of the fetus. The influence of Nimbeks^® The reproductive function was not studied.

The use of nimbeks^® Pregnancy may only, when the intended benefits to the mother outweighs the potential risk to the fetus.

Unknown, Is Cisatrakuria a Bezilat or its metabolites with breast milk in humans is released.

Cautions

Cisatrakuria Besilate causes paralysis of the respiratory and skeletal muscles, but does not affect the consciousness and threshold of pain sensitivity.

Nahbeks^® Anesthesiologists or doctors of other specialties should be prescribed, having experience in the use of muscle relaxants.

When prescribing muscle relaxants, incl. Napex, it is necessary to observe neuromuscular conductivity, to choose the necessary individual dose of the drug. Given the possibility of cross reactions between muscle relaxants, Particular caution should be observed with the introduction of nibeks^® patients, which had hypersensitivity reactions to other muscle relaxants, since a high frequency of occurrence of cross -sensitivity was revealed (more 50%). Cisatrakuria Bezilate does not have pronounced wagonical or ganglon, Therefore, Nimbeks^® does not have a clinically significant effect on heart rate and does not affect the bradycardia, caused by many means for anesthesia or stimulation of the vagus nerve during surgery.

In patients with miastenia and other forms of neuromuscular diseases, sensitivity to incomeling muscle relaxants is significantly increased. Recommended initial dose of nimbeks^® in such patients should not exceed 20 mg / kg.

Severe disorders of acid-base balance and/or electrolyte metabolism can increase or reduce patients' sensitivity to muscle relaxants.

The influence of Nimbeks^® A history of malignant hyperthermia was not studied.

The influence of cisatrakuria of bezilate on patients with burns was also not studied. However, when prescribing nibeks to such patients^®, Like other non -trapping muscle relaxants, it is necessary to keep in mind a large dose and lower duration of the drug in them. Nahbeks^® is a hypotonic solution and should not be introduced into the infusion system, through which blood transfusion is carried out.

Patients in intensive care units

The introduction of ladanosine animals (Metabolita Cisatracuria Narroth and attractions of bezylate) In high doses, it was associated with transient arterial hypotension and in some cases – with symptoms of the excitation of the cerebral cortex. There are separate reports on the development of seizures in patients in OIT, who received atrakuria bezilate in combination with other drugs. These patients usually had one or more diseases, predisposing seizures (eg, traumatic brain injury, hypoxic encephalopathy, swelling of the brain, viral encephalitis, uremia), Therefore, the causal relationship of the development of seizures with laudanosine has not been established. It will be appreciated, that the concentration of laudanosine in the blood plasma when the niobex is introduced^® about 3 half, than with infusion of atracuria Bezilate.

Overdose

Symptoms: With an overdose, the expected symptoms are due to prolonged paralysis of skeletal and respiratory muscles and its consequences.

Treatment: To restore adequate spontaneous breathing, it is very important to maintain lung ventilation and blood oxygenation. Nahbeks^® does not affect consciousness, Therefore, the patient should be under the influence of sedatives. When there are signs of spontaneous restoration, it can be accelerated by introducing anticholinestural means.

Drug Interactions

With joint use, the effect of muscle relaxants enhance: Means for anesthesia (Flying substances, Such as Enfluran, Izofluran and Galotan), ketamine, Other non-depolarizing muscle relaxants; antibiotics (incl. aminoglikozidy, Polymyxin, spectinomycin, tetracikliny, lincomycin and clindamycin), antiaritmiki (Including Prranolol, Calcium channel blockers, lidokain, procainamide and quinidine), Diuretic (incl. furosemide and, perhaps, tiazidы, Manitol and acetazolamide), magnesium salts, lithium salt, ganglioblokatorы (trimetafan, geksametonïy).

The preceding prolonged use of phenytoid or carbamazepine weakens the effect of muscle relaxants.

The preliminary administration of succession does not affect the duration of the neuromuscular blockade, caused by the bolus introduction of a nibeks^®, and does not change the infusion rate of the drug.

Introduction of succession to increase the duration of neuromuscular blockade, caused by non-depolarizing muscle relaxants, It can lead to a long and complex blockade, which can be difficult to eliminate using anticholinestural means.

In rare cases, some drugs can worsen the course or contribute to the manifestation of latent myasthenia, and also cause myasthenic syndrome, And as a result, an increased sensitivity to incomeling muscle relaxants may be observed. Similar drugs include various antibiotics, Beta-adrenergic receptors blockers (propranolol, oxprenolol), antiarrhythmics (prokaynamyd, quinidine), Antoremplime means (chloroquine, D-Penicillamine), trimetafan, chlorpromazine, steroids, phenytoin and lithium preparations.

Therapy antiholinesteraznami drugs, often used for the treatment of Alzheimer's disease, eg, donepezilom, can shorten the duration of the neuromuscular blockade and loosen the blocking effect of nibex^®.

Pharmaceutical interaction

When introduced in conditions, imitating an infusion system with a Y-shaped catheter, Nahbeks^® Compatible with the following drugs, usually used during surgery: Droperidol, fentanyl citrate, Midazolam hydrochloride.

The drug is incompatible with ketorolac, Trometamol or injection emulsion of propofol.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

A List. The drug should be stored in the dark, inaccessible to children at 2 ° to 8 ° C; Do not freeze. Shelf life – 2 year.