Cisatracurium besylate solution 2mg/ml 5ml ampoules, 5pcs

Composition

Per 1 ml: Active ingredient:  cisatracurium bezylate-2.68 mg (in terms of cisatracurium-2.0 mg); Excipients:  benzenesulfonic acid solution 32% – up to pH 3.0-3.8, water for injection – up to 1.0 ml

Pharmacological action

Pharmacotherapy group:

non-depolarizing muscle relaxant of peripheral action

ATX code: M 03 AC 11

Pharmacological properties

Cisatracurium bezylate is a non-depolarizing benzylisoquinoline muscle relaxant of medium duration of action.

Pharmacodynamics

According to clinical studies in men, cisatracurium bezilate at a dose up to 8 times the effective dose required for 95% suppression of the response of the abductor muscle of the thumb in response to ulnar nerve stimulation (ED 95) does not cause dose-dependent histamine release. Cisatracurium bezylate binds to the cholinergic receptors of motor nerve endings and acts as an acetylcholine antagonist, causing a competitive blockade of neuromuscular conduction, which can be quickly eliminated by cholinesterase inhibitors, for example, neostigmine methylsulfate and edrophonium chloride.

The ED 95 of cisatracurium bezylate during opioid anesthesia (sodium thiopental, fentanyl, and midazolam) is 0.05 mg / kg.

The ED 95 of cisatracurium bezylate in children during halothane anesthesia is 0.04 mg / kg

. Pharmacokinetics

The non-compartment pharmacokinetics of cisatracurium bezilate do not depend on the dose in the studied range (from 0.1 to 0.2 mg / kg, i. e. from 2 to 4 × ED 95). Population pharmacokinetic modeling confirms and extends this range to 0.4 mg / kg (8 × ED 95).

Distribution

After use of 0.1 and 0.2 mg/kg cisatracurium bezylate as an injection to adult surgical patients, the volume of distribution at steady state is from 121 to 161 ml/kg.

Metabolism

Cisatracurium bezylate breaks down in the body at physiological pH and body temperature (Hofmann elimination) to form laudanosine and a mono-quaternary acrylate metabolite, which undergoes hydrolysis under the action of non-specific plasma esterase to form a mono-quaternary alcohol metabolite. Metabolites do not have muscle-relaxing properties.

Deduction

The elimination of cisatracurium bezylate is mainly organ-independent, however, elimination through the liver and kidneys is the primary route of clearance of its metabolites.

The pharmacokinetic parameters of the drug administered as bolus injections in doses above 0.1 and 0.2 mg / kg to adult surgical patients are presented in the table.

Average values of pharmacokinetic data corresponding to the limits of average cisatracurium doses

Pharmacokinetics with infusion use

, the pharmacokinetics of cisatracurium bezilate after injection of the drug as an infusion and bolus are the same. The average clearance of cisatracurium bezylate is 6.9 ml / kg / min, and the elimination half-life is 28 minutes. Elimination of the drug does not depend on the duration of the infusion and does not differ from that with its bolus use.

Special patient groups

Elderly patients

There is no clinically significant difference in the pharmacokinetics of cisatracurium bezilate in young and elderly patients, its plasma clearance does not change depending on age according to a comparative study. A small increase in the volume of distribution (+17%) and half-life (+ 4 min) did not affect the recovery time of neuromuscular conduction in elderly patients.

Patients with impaired renal function

There was no clinically significant difference in the pharmacokinetics of cisatracurium bezilate in patients with end-stage renal failure and in healthy volunteers. According to the comparative study, there were no statistically significant or clinically significant differences in the pharmacokinetic parameters of cisatracurium bezilate. The recovery time of neuromuscular conduction also does not change in renal failure.

Patients with impaired liver function

There was no clinically significant difference in the pharmacokinetics of cisatracurium bezilate in patients with end-stage hepatic insufficiency and in healthy volunteers. In a comparative study in patients receiving liver transplantation and healthy patients, there was a slight difference in the volume of distribution (+ 21%) and clearance (+ 16%) of cisatracurium bezilate, but the drug half-life and recovery time of neuromuscular conduction did not change.

Intensive Care unit (ICU)patients

The pharmacokinetics of cisatracurium bezilate in ICU patients receiving it as a long-term infusion do not differ from those in healthy adults or from the pharmacokinetics of a single bolus use. The average clearance of cisatracurium bezylate is 7.5 ml / kg / min and the elimination half-life is 27 minutes. The recovery time of the drug after prolonged infusion does not depend on the duration of the infusion. The concentration of metabolites is higher in those patients in the ICU who have impaired renal and/or liver function. However, these metabolites do not affect neuromuscular blockade.

Indications

The drug Cisatracurium bezilat is used during surgical operations, other interventions and in the intensive care unit. It is used for myoplegia as an adjunct to general anesthesia or ICU sedation, for tracheal intubation, and for mechanical ventilation.

Use during pregnancy and lactation

Fertility Effects on reproductive function have not been studied. Pregnancy Cisatracurium bezilate should only be used during pregnancy if the expected benefit to the mother outweighs the potential risk to the fetus. Teratogenicity Animal studies have shown that the drug cisatracurium bezylate does not have a teratogenic and toxic effect on the fetus. Breast-feeding Periodit is not known whether cisatracurium bezylate or its metabolites are excreted in human breast milk. The drug should be used during breastfeeding only if the expected benefit to the mother outweighs the potential risk to the child.

Contraindications

Hypersensitivity to cisatracurium bezylate, atracurium bezylate, benzenesulfonic acid and other bis-benzylisoquinoline derivatives.

With caution

It should be used with caution in cases of acid-base and electrolyte imbalance; carcinomatosis or neuromuscular diseases (including myasthenia gravis and myasthenic syndrome) or other conditions that may lead to prolonged neuromuscular block; burns; hemiparesis or paraparesis.

Side effects

The adverse reactions listed below are listed according to the lesion of organs and organ systems and frequency of occurrence. The frequency of occurrence is determined as follows:  very common (≥1/10), common (≥1/100 and <1/10), infrequent (≥1/1,000 and <1/100), rare (≥1/10000 and <1/1000), very rare ( Frequency categories were formed based on clinical studies of the drug and post-marketing surveillance. Data from clinical studiesbreak from the heart often: bradycardia. Vascular disorders are common: decreased blood pressure; Infrequently: redness of the skin. Respiratory, thoracic, and mediastinal disorders often: bronchospasm. Disorders of the skin and subcutaneous tissue often: a rash.

Data from post-marketing surveillance of immune system disorders are very rare: anaphylactic reactions. Anaphylactic reactions may vary in severity and severity after use of muscle relaxants. Very rarely, severe anaphylactic reactions have been reported in patients treated with Cisatracurium bezilate in combination with one or more anesthetics. Musculoskeletal and connective tissue disorders are very rare: myopathy, muscle weakness. Several cases of myopathy and/or muscle weakness have been reported with prolonged use of muscle relaxants in severe patients in the intensive care unit, most of whom received concomitant corticosteroid therapy. A causal relationship with the use of cisatracurium bezilate in these rare cases has not been established.

Interaction

Many drugs have an effect on the severity and/or duration of action of non-depolarizing muscle relaxants.

Enhance the effect of muscle relaxants

General anesthesia products: – means for inhalation anesthesia, such as enflurane, isoflurane and halothane;- ketamine; – other non-depolarizing muscle relaxants;

Other medications: – antibiotics, including aminoglycosides, polymyxins, spectinomycin, tetracyclines, lincomycin and clindamycin;- antiarrhythmic drugs, including propranolol, slow calcium channel blockers, lidocaine, procainamide and quinidine;- diuretics, including furosemide and possibly thiazides, mannitol and acetazolamide;- magnesium salts;- lithium salts;- ganglion blocking drugs: trimetafan camzylate, hexamethonium benzosulfonate.

In rare cases, certain medications may worsen the course or contribute to the manifestation of latent myasthenia gravis or cause myasthenic syndrome, resulting in increased sensitivity to non-depolarizing muscle relaxants. Such drugs include various antibiotics, beta-blockers (propranolol, oxprenolol), antiarrhythmic drugs (procainamide, quinidine), antirheumatic drugs (chloroquine, penicillamine), trimetafan camzilate, chlorpromazine, steroids, phenytoin and lithium.

The use of suxamethonium to increase the duration of neuromuscular blockade caused by non-depolarizing muscle relaxants can lead to long-term complex blockade, which can be difficult to eliminate with cholinesterase inhibitors.

Reduce the effect of muscle relaxants-previous long-term use of phenytoin or carbamazepine; – therapy with cholinesterase inhibitors, often used to treat Alzheimer’s disease, for example, donepezil, can shorten the duration of neuromuscular blockade and weaken the blocking effect of the drug Cisatracurium bezilat.

No effect-pre – use of suxamethonium does not affect the duration of neuromuscular blockade caused by bolus use of Cisatracurium bezilate, and should not be taken into account when choosing the infusion rate of the drug.

When administered under conditions that mimic an infusion system with a Y-shaped catheter, Cisatracurium bezylate is compatible with the following drugs commonly used during surgery: alfentanyl hydrochloride, droperidol, fentanyl citrate, midazolam hydrochloride, and sufentanyl citrate. The drug is not compatible with ketorolac trometamol and propofol emulsion for intravenous use.

How to take, course of use and dosage

Cisatracurium bezylate solution for intravenous use does not contain antimicrobial preservatives and is intended for use to one patient.

Bolus intravenous use

Adults

Tracheal intubation

For tracheal intubation in adults, the recommended dose of Cisatracurium bezilate, which should be administered quickly within 5-10 seconds, is 0.15 mg / kg and provides optimal conditions for tracheal intubation within 120 seconds after injection.

With higher doses of the drug, neuromuscular blockage occurs faster. The table shows the average pharmacodynamic parameters of Cisatracurium bezilate when administered in doses from 0.1 to 0.4 mg / kg to healthy adult volunteers during opioid anesthesia (sodium thiopental, fentanyl and midazolam) or propofol anesthesia.

Average values of pharmacodynamic data within the average dose values of Cisatracurium bezilate

91a is a single contraction of the adductor muscle of the thumb, as well as its first contraction in response to a series of four impulses during supramaximal electrical stimulation of the ulnar nerve.

Enflurane or isoflurane can extend the duration of blockage caused by the initial dose of Cisatracurium bezilate by 15%.

Maintenance dose

The duration of neuromuscular blockade can be increased with maintenance doses of Cisatracurium bezilate. Thus, during anesthesia with opioids or propofol, the drug Cisatracurium bezilate at a dose of 0.03 mg / kg prolongs the neuromuscular blockade by approximately 20 minutes. However, subsequent use of maintenance doses does not lead to progressive prolongation of the blockade.

Spontaneous recovery

After spontaneous recovery of neuromuscular conduction has begun, its rate does not depend on the administered dose of Cisatracurium bezilate. During anesthesia with opioids or propofol, the average recovery time of neuromuscular conduction from 25 to 75% and from 5 to 95% is approximately 13 minutes and 30 minutes, respectively.

Reversibility

The neuromuscular blockade caused by Cisatracurium bezylate is easily eliminated by cholinesterase inhibitors in standard doses. After use of a cholinesterase inhibitor at an average of 10% T1 of conductivity recovery, the average time to restore conductivity from 25 to 75% and to complete recovery (T4:T1 ratio ≥0.7) is approximately 4 minutes and 9 minutes, respectively.

Children aged 1 month to 12 years

Tracheal intubation

As in adults, the initial dose of Cisatracurium bezilate for tracheal intubation in children is 0.15 mg / kg, which is administered quickly intravenously within 5-10 seconds and creates optimal conditions for tracheal intubation within 120 seconds after injection. Pharmacodynamic data for these doses are presented in the tables below. Based on pharmacodynamic data, an initial dose of Cisatracurium bezylate 0.1 mg/kg is recommended to ensure a shorter neuromuscular blockade; in this case, similar conditions for tracheal intubation are created 120-150 s after use of the drug. Cisatracurium bezilate has not been studied for intubation in children with ASA class III-IV. Data on the use of Cisatracurium bezilate in children under 2 years of age during long-term or large operations are limited.

When using the drug Cisatracurium bezilat in children aged from 1 month to 12 years, the duration of neuromuscular blockade decreases, and its spontaneous recovery occurs faster than in adults under the same anesthesia conditions. There are minor differences in the pharmacodynamic parameters of Cisatracurium bezilate in children aged 1 to 11 months from those in children aged 1 to 12 years. Pharmacodynamic parameters of the drug Cisatracurium bezilat in children aged from 1 to 11 months and from 1 to 12 years are presented in the tables.

Children aged from 1 to 11 months

Children aged 1 to 12 years

If Cisatracurium bezilate is not used for intubation: a dose of less than 0.15 mg/kg may be used. Pharmacodynamic data for doses of 0.08 and 0.1 mg / kg for children aged 2 to 12 years are presented in the table below:

Halothane can increase the duration of neuromuscular blockade caused by Cisatracurium bezilate by no more than 20%. There is no information about the use of Cisatracurium bezilate in children during anesthesia with isoflurane or enflurane, but it can be expected that these inhaled anesthetics can also increase the duration of neuromuscular blockade caused by the drug by no more than 20%.

Maintenance dose (children aged 2-12 years)

The duration of neuromuscular blockade can be increased by use of Cisatracurium bezilate in maintenance doses. During halothane anesthesia, use of Cisatracurium bezilate to children aged 2 to 12 years at a dose of 0.02 mg/kg increases the duration of neuromuscular blockade by approximately 9 minutes. However, subsequent use of maintenance doses does not lead to progressive prolongation of the blockade.

There is insufficient data to provide specific recommendations for the selection of maintenance dose in children under 2 years of age. However, very limited data from clinical studies in children under 2 years of age indicate that a maintenance dose of 0.03 mg / kg can prolong clinically effective neuromuscular blockade for up to 25 minutes under opioid anesthesia.

Spontaneous recovery

After spontaneous recovery of neuromuscular conduction has begun, its rate does not depend on the administered dose of Cisatracurium bezilate. During anesthesia with opioids or halothane, the average time to restore conductivity from 25 to 75% and from 5 to 95% is approximately 11 minutes and 28 minutes, respectively.

Reversibility

The neuromuscular blockade caused by Cisatracurium bezylate is easily eliminated by cholinesterase inhibitors in standard doses. The average time of recovery of conductivity from 25 to 75% and to complete recovery (coefficient T4:t1≥0.7) after use of a cholinesterase inhibitor, on average at 13% T1 of recovery of conductivity, is approximately 2 minutes and 5 minutes, respectively.

Infusion introduction

Adults and children aged 2-12 years

To maintain neuromuscular blockade, Cisatracurium bezilate can be administered by infusion. An initial infusion rate of 3 mcg/kg/min (0.18 mg/kg/h) is recommended to restore T1 blockade at the level of 89-99% after signs of spontaneous recovery of neuromuscular conduction. After initial stabilization of neuromuscular blockade, an infusion rate of 1-2 micrograms/kg/min (0.06-0.12 mg/kg/h) is sufficient to maintain it at this level in most patients.

During anesthesia with isoflurane or enflurane, it may be necessary to reduce the infusion rate of Cisatracurium bezilate by 40%.

The rate of infusion depends on the concentration of cisatracurium bezylate in the infusion solution, the required depth of neuromuscular blockade, and the patient’s body weight.

The table shows recommendations for the introduction of an undiluted solution of Cisatracurium bezylate.

Infusion rate of Cisatracurium bezylate, solution for intravenous use 2 mg / ml

Continuous infusion of Cisatracurium bezilate at a constant rate is not accompanied by a progressive increase or decrease in neuromuscular blockade.

After stopping the infusion of Cisatracurium bezilate, spontaneous recovery of neuromuscular conduction occurs at a rate comparable to that after a single bolus use of the drug. Despite the fact that Cisatracurium bezilate infusion has not been specifically studied in children under 2 years of age, similar to bolus doses, it can be assumed that the infusion rate in this age group should be the same as in older children.

Special patient groups

Newborns under 1 month of age

There are no data on the use of Cisatracurium bezilate in children under 1 month of age, so it is impossible to give recommendations on the dosage of the drug in this age group.

Elderly patients

No dose adjustment is required in elderly patients. The pharmacodynamics of Cisatracurium bezilate are similar to those of young patients, but the effect of the drug, like other muscle relaxants, may begin somewhat later.

Patients with impaired renal function

No dose adjustment is required in patients with renal insufficiency. The pharmacodynamics of Cisatracurium bezilate are similar to those in patients with normal renal function, but the drug’s effect may begin somewhat later.

Patients with impaired liver function

No dose adjustment is required in patients with end-stage hepatic insufficiency. The pharmacodynamics of Cisatracurium bezilate are similar to those of patients with normal liver function, but the effect of Cisatracurium bezilate may begin somewhat earlier.

Patients with diseases of the cardiovascular system

Rapid use of Cisatracurium bezilate (within 5-10 seconds) as a bolus at any studied dose (up to 0.4 mg / kg inclusive (8 × ED 95)) patients with severe cardiovascular diseases (NYHA functional class I-III, who underwent coronary artery bypass grafting) are not accompanied by clinically significant reactions from the cardiovascular system.

There are no data on the use of Cisatracurium bezilat in children undergoing cardiac surgery.

Use in intensive care units (ICUs)

Cisatracurium bezilate can be administered intravenously (as a bolus) and/or drip (as an infusion) to adult ICU patients.

For adult ICU patients, the recommended initial infusion rate of Cisatracurium bezilate is 3 mcg / kg / min (0.18 mg / kg / h). The required dose varies widely from patient to patient and may increase or decrease over time. In clinical trials, the average infusion rate was 3 mcg / kg / min [0.5 to 10.2 mcg / kg / min (0.03 to 0.6 mg / kg / h)].

The average time to complete spontaneous recovery of conduction after prolonged (up to 6 days) infusion of Cisatracurium bezilate in ICU patients is approximately 50 minutes.

Recovery of conductivity after Cisatracurium bezilate infusion in ICU patients does not depend on the duration of the infusion.

Use in patients undergoing hypothermic heart surgery

There are no data on the use of Cisatracurium bezilate during cardiac surgery in hypothermia (25-28 °C). As with other muscle relaxants, the infusion rate required to maintain adequate surgical muscle relaxation under these conditions is expected to be significantly reduced.

Monitoring

As with other muscle relaxants, monitoring of neuromuscular function is recommended when using Cisatracurium bezilate for individual dose selection.

Instructions for using the solution

The diluted solution of Cisatracurium bezylate for intravenous use is stable for at least 24 hours at a temperature of 5 to 25°C at concentrations of 0.1 to 2.0 mg / ml in the following solutions for intravenous use (in polyvinyl chloride or polypropylene containers):

– sodium chloride solution for infusions of 0.9% (by mass fraction);- dextrose solution for infusions of 5% (by mass fraction);- sodium chloride solution 0.18% (by mass fraction) and dextrose 4% (by mass fraction) for infusions;- a solution of sodium chloride 0.45% (by mass fraction) and dextrose 2.5% (by mass fraction) for infusions.

Since the drug does not contain antimicrobial preservatives, its dilution should be carried out immediately before use, the diluted solution should be immediately administered, and the unused solution of the drug Cisatracurium bezylate should be destroyed. Cisatracurium bezylate is chemically unstable when diluted in Ringer’s solution.

When other drugs are administered through the same needle or cannula through which Cisatracurium bezilate was administered, it is recommended to wash the needle and cannula after use of each drug with a sufficient amount of a compatible solution for intravenous use, for example,0.9% sodium chloride solution (by mass fraction).

Cisatracurium bezylate is stable only in acidic solutions, so it should not be mixed in the same syringe or administered simultaneously through the same needle with alkaline solutions, for example, with sodium thiopental. If a small-caliber peripheral vein is used for injection of Cisatracurium bezilate, it should be flushed after the drug is administered

a compatible solution for intravenous use, for example,0.9% sodium chloride solution (by mass fraction).

Overdose

Symptoms The main symptoms of Cisatracurium bezilate overdose are prolonged muscle paralysis, including respiratory paralysis, and its consequences. Treatment To restore adequate spontaneous breathing, it is very important to maintain ventilation and blood oxygenation. Complete sedation is necessary, as the drug Cisatracurium bezilate does not affect consciousness. If there are signs of spontaneous recovery of neuromuscular conduction, it can be accelerated with the help of cholinesterase inhibitors. use of 0.04-0.7 mg / kg of neostigmine methyl sulfate with 10% reduction in conductivity provides 95% reduction (T4:T1 ratio>=0.7) on average for 9 to 10 minutes. The time of recovery of conductivity from 25% to complete recovery (the ratio of T4:T1>=0.7) with the use of these doses of neostigmine methyl sulfate reaches 7 minutes. The average recovery index from 25% to 75% is 3 to 4 minutes. use of edrofonium chloride at a dose of 1.0 mg / kg with approximately 25% recovery of the neuromuscular block (16-30%) provides 95% recovery (T4:t1 ratio>=0.7) on average for 3 to 5 minutes.

Purpose

Cisatracurium bezilate causes paralysis of the respiratory and skeletal muscles, but does not affect consciousness or the threshold of pain sensitivity. The drug Cisatracurium bezilat should be prescribed by anesthesiologists or doctors of other specialties who have experience in using muscle relaxants. It is necessary to ensure the availability and availability of equipment for tracheal intubation and maintenance of pulmonary ventilation and adequate blood oxygen saturation. When prescribing muscle relaxants, including Cisatracurium bezilate, it is necessary to monitor neuromuscular conduction in order to select the necessary individual dose of the drug. Special care should be taken when using Cisatracurium bezilat in patients who have experienced hypersensitivity reactions to other muscle relaxants, since a high frequency of cross-sensitivity between muscle relaxants (more than 50%) has been detected. Cisatracurium bezilate does not have pronounced M-holinoblocking or ganglioblocking properties, so the drug Cisatracurium bezilate does not have a clinically significant effect on heart rate and does not affect bradycardia caused by many means of anesthesia or vagus nerve stimulation during surgery. Patients with myasthenia gravis and other forms of neuromuscular diseases have significantly increased sensitivity to non-depolarizing muscle relaxants. The recommended initial dose of Cisatracurium bezilate in such patients should not exceed 0.02 mg / kg. Severe disturbances in acid-base balance and / or electrolyte metabolism may increase or decrease the sensitivity of patients to muscle relaxants. The effect of Cisatracurium bezilate on patients with a history of malignant hyperthermia has not been studied. Studies conducted on animals (pigs) susceptible to malignant hyperthermia have shown that the drug Cisatracurium bezilate does not cause this syndrome. Patients undergoing surgery with induced hypothermia No studies have been conducted on Cisatracurium bezilate in patients undergoing surgery with induced hypothermia (from 25 to 28 °C). As with other muscle relaxants, the infusion rate required to maintain adequate surgical muscle relaxation under these conditions is expected to be significantly reduced. The effect of Cisatracurium bezilate in patients with burns has also not been studied. However, when prescribing Cisatracurium bezilate to such patients, as well as other non-depolarizing muscle relaxants, it is necessary to keep in mind the larger dose and shorter duration of action of the drug. The drug Cisatracurium bezilate is a hypotonic solution and should not be introduced into the infusion system through which blood transfusion is performed. Patients with hemi-and paraparesis with injuries of the lower extremities may also show resistance to the action of non-depolarizing muscle relaxants. For correct dose selection, it is necessary to monitor the neuromuscular block on the unaffected limb. Patients in intensive care units (ICUs)High-dose use of laudanosine (a metabolite of cisatracurium bezilate and atracurium bezilate) to animals was associated with a transient decrease in blood pressure and, in some cases, with symptoms of cortical arousal. In the most sensitive animal species, reactions to laudanosine were observed at concentrations comparable to those achieved in some patients in OPT after prolonged infusion of atracurium. There are isolated reports of seizures in ICU patients who received atracurium bezilate in combination with other medications. Since they usually suffered from one or more diseases predisposing to seizures (for example, traumatic brain injury, hypoxic encephalopathy, cerebral edema, viral encephalitis, uremia), a causal relationship between the development of seizures and laudanosine has not been established. In addition, it should be borne in mind that the concentration of laudanosine in the blood plasma with the introduction of the drug Cisatracurium bezilate is approximately 3 times less than with the infusion of atracurium bezilate.

Influence on the ability to drive vehicles and mechanisms

The drug Cisatracurium bezilate is always used during anesthesia, therefore, the effect on the ability to drive a car or other moving mechanisms will be the same as that of drugs for anesthesia. If an early discharge is required after the use of Cisatracurium bezilat, patients should not drive vehicles or operate mechanisms.

Special instructions

Cisatracurium bezilate causes paralysis of the respiratory and skeletal muscles, but does not affect consciousness or the threshold of pain sensitivity. The drug Cisatracurium bezilat should be prescribed by anesthesiologists or doctors of other specialties who have experience in using muscle relaxants. It is necessary to ensure the availability and availability of equipment for tracheal intubation and maintenance of pulmonary ventilation and adequate blood oxygen saturation.

When prescribing muscle relaxants, including Cisatracurium bezilate, it is necessary to monitor neuromuscular conduction in order to select the necessary individual dose of the drug.

Special care should be taken when using Cisatracurium bezilat in patients who have experienced hypersensitivity reactions to other muscle relaxants, since a high frequency of cross-sensitivity between muscle relaxants (more than 50%) has been detected.

Cisatracurium bezilate does not have pronounced M-holinoblocking or ganglioblocking properties, so the drug Cisatracurium bezilate does not have a clinically significant effect on heart rate and does not affect bradycardia caused by many means of anesthesia or vagus nerve stimulation during surgery.

Patients with myasthenia gravis and other forms of neuromuscular diseases have significantly increased sensitivity to non-depolarizing muscle relaxants. The recommended initial dose of Cisatracurium bezilate in such patients should not exceed 0.02 mg / kg.

Severe disturbances in acid-base balance and / or electrolyte metabolism may increase or decrease the sensitivity of patients to muscle relaxants.

The effect of Cisatracurium bezilate on patients with a history of malignant hyperthermia has not been studied.

Studies conducted on animals (pigs) susceptible to malignant hyperthermia have shown that the drug Cisatracurium bezilate does not cause this syndrome.

Patients undergoing surgery with induced hypothermia

Cisatracurium bezilate has not been studied in patients undergoing surgery with induced hypothermia (from 25 to 28 °C). As with other muscle relaxants, the infusion rate required to maintain adequate surgical muscle relaxation under these conditions is expected to be significantly reduced.

The effect of Cisatracurium bezilate in patients with burns has also not been studied. However, when prescribing Cisatracurium bezilate to such patients, as well as other non-depolarizing muscle relaxants, it is necessary to keep in mind the larger dose and shorter duration of action of the drug.

The drug Cisatracurium bezilate is a hypotonic solution and should not be introduced into the infusion system through which blood transfusion is performed.

Patients with hemi-and paraparesis with injuries of the lower extremities may also show resistance to the action of non-depolarizing muscle relaxants. For correct dose selection, it is necessary to monitor the neuromuscular block on the unaffected limb.

Patients in intensive care units (ICUs)

High-dose use of laudanosine (a metabolite of cisatracurium bezilate and atracurium bezilate) to animals was associated with a transient decrease in blood pressure and, in some cases, with symptoms of cortical arousal. In the most sensitive animal species, reactions to laudanosine were observed at concentrations comparable to those achieved in some patients in OPT after prolonged infusion of atracurium.

There are isolated reports of seizures in ICU patients who received atracurium bezilate in combination with other medications. Since they usually suffered from one or more diseases predisposing to seizures (for example, traumatic brain injury, hypoxic encephalopathy, cerebral edema, viral encephalitis, uremia), a causal relationship between the development of seizures and laudanosine has not been established.In addition, it should be borne in mind that the concentration of laudanosine in the blood plasma with the introduction of the drug Cisatracurium bezilate is approximately 3 times less than with the infusion of atracurium bezilate.

Influence on the ability to drive vehicles and mechanisms

The drug Cisatracurium bezilate is always used during anesthesia, therefore, the effect on the ability to drive a car or other moving mechanisms will be the same as that of drugs for anesthesia.

If an early discharge is required after the use of Cisatracurium bezilat, patients should not drive vehicles or operate mechanisms.

Storage conditions

In a dark place at a temperature of 2 °C to 8 °C. Do not freeze it. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Cisatracurium bezylate

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection