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

Active substanceRokuronium bromideRokuronium bromide

Similar drugsTo uncover

Croaron

solution in / in

LENS-PHARM, LLC Russia

Roqueronius Kabi

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Fresenius Kabi Deutschland GmbH Germany

Roelax

solution in / in

KE G Laboratories (Yu Kay) Limited United Kingdom

Esmeron®

solution in / in

Organon, N.V. Netherlands

Dosage form: & nbspSolution for intravenous administration

Composition:

Active substance

Rokuronium bromide - 10 mg.

Excipients

Sodium acetate trihydrate 2.0 mg,

Sodium chloride 3.3 mg,

Acetic acid is ice - up to pH 4.0,

Water for injection - up to 1 ml.

Description:Transparent from colorless to light brown liquid

Pharmacotherapeutic group:Nondepolarizing muscle relaxant of peripheral action.

ATX: & nbsp

M.03.A.C Other quaternary ammonium compounds

M.03.A.C.09 Rokuronium bromide

Pharmacodynamics:

Mechanism of action

Rokuroniya bromide is a high-speed, non-depolarizing intermediate relaxant muscle relaxant with all the pharmacological effects (kurarepodobnymi), characteristic for this class of drugs. It competitively blocks the n-holinoretseptory end plate of motoneurons. Antagonists of this action are cholinesterase inhibitors, such as neostigmine methylsulfate, edrophonium chloride and pyridostigmine bromide.

Pharmacodynamic effects

ED₉₀ (the dose necessary to suppress the contractile response of the long flexor of the thumb of the wrist by 90% in a report on stimulation of the ulnar nerve) with intravenous general anesthesia is about 0.3 mg / kg rocuronium bromide. ED₉₅ in infants is lower than in adults and children older than 2 years (0.25, 0.35 and 0.40 mg / kg, respectively). The clinical duration of action (time to spontaneous recovery of the contractile ability of skeletal muscles to 25% of the original value) at a dose of 0.6 mg / kg rocuronium bromide is 30-40 minutes. The total duration (time to spontaneous recovery of the contractile ability of skeletal muscles to 90% of the original value) is 50 minutes. The average time of spontaneous recovery of the contractility of skeletal muscles from 25 to 75% of the initial value (recovery index) after a bolus dose of 0.6 mg / kg rocuronium bromide is 14 minutes. At lower doses (0.3-0.45 mg / kg of rocuronium bromide (1-1,5xED₉₀)) The beginning of the action comes later, and the duration of the action is shorter. At high doses of 2 mg / kg rocuronium bromide, the clinical duration of action is 110 minutes.

Intubation of the trachea during routine anesthesia

Within 60 seconds after intravenous administration of 0.6 mg / kg of rocuronium bromide (2xED₉₀ with intravenous anesthesia), almost all patients achieve a state acceptable for intubation, and in 80% of them, the conditions for intubation are regarded as excellent. General relaxation of skeletal muscles, sufficient for any surgical intervention, is achieved within 2 minutes. After administration of 0.45 mg / kg rocuronium bromide, acceptable conditions for intubation are created after 90 seconds.

Fast sequential induction of anesthesia

With rapid sequential induction of anesthesia with propofol or fentanyl / thiopental sodium, after the administration of 1 mg / kg of rocuronium bromide, 93% and 96% of patients, respectively, after 60 seconds, are suitable for intubation conditions. Of these, 70% of patients are regarded as excellent. The clinical duration of action of rocuronium bromide at this dose is about 1 hour, after which the neuromuscular conduction can be restored. With rapid sequential induction of anesthesia with propofol or fentanyl / thiopental sodium, after administering 0.6 mg / kg of rocuronium bromide, in 81% and 75% of patients, respectively 60 seconds are acceptable for intubation conditions.

Children

The average time of onset of action in infants and children over 1 year with an intubation dose of 0.6 mg / kg rocuronium bromide is somewhat shorter than in adults. Comparison between different age groups has shown that the onset of action in newborns and adolescents occurs on average a little faster (in 1 min) than in infants (up to 1-2 months), children 3-23 months and children 2-11 years (0, 4, 0.6 and 0.8 min respectively). In children compared with infants and adults, the duration and time of recovery of neuromuscular conduction may be shorter. A comparison between different age groups showed that the average recovery time T₃ in newborns and infants, a longer (56.7 and 60.7 min, respectively) than in children aged 3-23 months, 2-11 years, and adolescents (45.4, 37.6 and 42.9 min, respectively).

Mean (standard deviation) start time and clinical duration of action after administration of 0.6 mg / kg of rocuronium bromide as initial intubation dose * during (maintenance) anesthesia with sevoflurane / dinitrogen oxide or isoflurane / dinitrogen oxide in children

	Time to maximum	Time to recovery
	blockade **, mines	T3 **, min
Newborns (0-27	0,98 (0,62)	56,69 (37,04)
days), n = 10		n = 9
1-2 months, n = 11	0.44 (0,19)	60,71 (16,52)
	n = 10
3-23 months	0,59 (0,27)	45,46 (12,94)
n = 28		n = 27
2-11 years old	0,84 (0,29)	37,58 (11,82)
n = 34
Adolescents (12-17 years old)	0,98 (0,38)	42,90 (15,83)
n = 31		n = 30

* The dose of rocuronium bromide, administered for 5 seconds.

** Calculated from the end of the administration of the intubation dose of rocuronium bromide.

Elderly patients, patients with diseases of the liver and (or) bile duct and (or) with renal insufficiency

The duration of action of maintenance doses (0.15 mg / kg) of rocuronium bromide with enflurane or isoflurane anesthesia may be somewhat greater in elderly patients and in patients with liver and / or kidney disease (approximately 20 minutes) than in patients without functional impairment Excretory organs with intravenous anesthesia (approximately 13 minutes). The cumulative effect (progressive increase in the duration of action) with repeated administration of the recommended maintenance doses was not observed.

Intensive Care Unit

After continuous infusion of rocuronium bromide in the intensive care unit, the recovery time train-of-the four (TOP) -relations (the ratio of the values of the fourth and first responses of the muscle to a four-digit (TOF) stimulation) to 0.7 depends on the degree of blockade at the end of the infusion. After a continuous infusion for 20 hours or more, the average time (range) between the reappearance of T2 (the second muscle response) in response to TOF- stimulation and recovery TOFratio to 0.7 is approximately 1.5 (1-5) hours in patients without multiple organ failure and 4 (1-25) hours in patients with multiple organ dysfunction.

Cardiovascular Surgery

In patients preparing for heart surgery, the most frequent changes observed during the development of the maximal block after the administration of 0.6-0.9 mg / kg of rocuronium bromide are a weak and clinically unexplained increase in the heart rate (up to 9%) and an increase in mean arterial pressure - up to 16% of the baseline values.

Restoration of neuromuscular conduction

Introduction of cholinesterase inhibitors (neostigmine methylsulfate, pyridostigmine bromide or eudrophonia chloride) upon the reappearance of T₂ or at the first signs of clinical recovery, blocks the action of rocuronium bromide.

Pharmacokinetics:

After intravenous administration of a single bolus dose of rocuronium bromide, the change in its concentration in the blood plasma passes through three exponential phases.In healthy adults, the mean terminal half-life (95% CI) is 73 (66-80) minutes, (apparent) volume of distribution under equilibrium conditions is 203 (193-214) ml / kg, plasma clearance is 3.7 (3.5 -3.9) ml / kg / min.

Rokuronium bromide is excreted in the urine and bile. Within 12-24 hours urinary excretion reaches 40%. After the administration of radioactively labeled rocuronium bromide, after 9 days, the excretion of radioactive label with urine was 47%, with feces - 43%. Approximately 50% is displayed unchanged. Plasma metabolites are not detected.

Children

Pharmacokinetics of rocuronium bromide in children (n= 146) at 0-17 years of age were studied using a population analysis of pooled pharmacokinetic data from two clinical trials using sevoflurane (induction) and isoflurane / dinitrogen oxide (maintaining anesthesia). It is shown that all pharmacokinetic parameters are linearly proportional to body weight (similar clearance, l / kg / h). The volume of distribution (l / kg) and terminal half-life (h) decreases with age. The following are pharmacokinetic (PK) parameters in children, grouped by age:

PK parameters (average [CO]) of rocuronium bromide in children with the use of sevoflurane and dinitrogen oxide (induction)and isoflurane / dinitrogen oxide (maintenance of anesthesia)

FC parameters	Age groups
	Newborns (0-27 days)	1-2 months	3-23 months	2-11 years old	adolescents
Cl, l / kg / h	0,31 (0,07)	0,3 (0,08)	0,33 (0,1)	0,35 (0,09)	0,29 (0,14)
Scope	0,42 (0,06)	0,31 (0,03)	0,23 (0,03)	0,18	0,18 (0,01)
distribution, l / kg				(0,02)
T_1/2β, h	1,1(0,2)	0,9 (0,3)	0,8 (0,2)	0.7 (0,2)	0.8 (0,3)

Elderly patients, patients with diseases of the liver and (or) bile duct and (or) with renal insufficiency

Plasma clearance in elderly patients and in patients with impaired renal function was slowed, but these differences in most studies did not reach statistical significance. In patients with hepatic insufficiency, the half-life increases by an average of 30 minutes, the clearance is reduced by 1 ml / kg / min (see also the section "Dosing and Administration").

Intensive Care Unit

With the introduction of rocuronium bromide in the form of continuous infusion to facilitate artificial ventilation for 20 hours or more, the average half-life and the average (apparent) volume of distribution in the equilibrium state of rocuronium bromide increase. In controlled clinical trials, a high interindividual variation was found, depending on the nature and extent of (poly) organ failure and the individual characteristics of the patient. In patients with (± SD) half-life was 21.5 (± 3.3) hours, (apparent) equilibrium volume of distribution was 1.5 (± 0.8) l / kg, and plasma clearance was 2.1 (± 0.8) ml / kg / min (see also section "Dosage and Administration").

Indications:Facilitating intubation of the trachea during planned surgical interventions and rapid sequential induction of anesthesia and providing relaxation of skeletal muscles during surgical interventions in adults and children from 1 month. Facilitation of tracheal intubation during rapid sequential induction and in intubation and mechanical ventilation in intensive care units in adults.

Contraindications:

Hypersensitivity to rocuronium or to bromide ion or to any auxiliary substance.

Pregnancy and lactation:

Pregnancy

Clinical data on the use of rocuronium bromide during pregnancy are absent. According to the results of preclinical studies, direct and indirect adverse effects on pregnancy, embryo / fetal development, labor and postnatal development have not been detected.

Cesarean section

In patients undergoing cesarean section, rocuronium bromide can be used as part of rapid consecutive induction of anesthesia, provided there is no risk of difficult intubation, the use of sufficient doses of anesthetics, or after intubation with suksamethonium. However, with the administration of rocuronium bromide at a dose of 0.6 mg / kg, conditions acceptable for intubation may not occur until the end of 90 seconds after administration. It is shown that this dose in women undergoing cesarean section is safe. Rokuronium bromide does not affect the Apgar score, the muscle tone of the fetus, or its cardiorespiratory adaptation. Only very small amounts of rocuronium bromide penetrate the placental barrier, which does not lead to clinically significant adverse reactions in the newborn.

Note 1: doses of 1 mg / kg were investigated in the rapid sequential induction of anesthesia, but not in patients undergoing cesarean section. Therefore, this group is recommended to enter only 0.6 mg / kg.

Note 2: since magnesium salts strengthen the neuromuscular block, in patients,receiving magnesium salts about the toxicity of pregnancy, recovery from a neuromuscular blockade caused by muscle relaxants may be slowed or inadequate. In this regard, in such patients, the dose of rocuronium bromide is reduced and matched depending on the contractile response.

Breast-feeding

Information on the ability of rocuronium bromide to penetrate into breast milk is absent. According to the results of preclinical studies rocuronium bromide Only in small amounts penetrated into breast milk. Rokuronium bromide in a small amount found in the milk of lactating rats. Data on the use of rocuronium bromide in the period of breastfeeding in humans are absent. Rokuronium bromide should be administered breast-feeding a woman only if the doctor finds that the benefits exceed the risks.

Dosing and Administration:

Dosing regimen

As well as other blockers of neuromuscular conduction, rocuronium bromide should be applied by experienced specialists (or under their control) who have experience in the use of such drugs.

Like other peripheral muscle relaxants, each patient should receive a dose of rocuronium bromide individually.When determining it, one should take into account the method of general anesthesia, the estimated duration of the operation, the possible interaction with other drugs administered before and (or) during anesthesia and the general condition of the patient.

In order to assess the degree of suppression and recovery of neuromuscular reactions, it is recommended to use the appropriate instrumental methods. Means for inhalation anesthesia enhance the blocking effect of rocuronium bromide on neuromuscular synapses. This enhancement, however, becomes clinically significant only when, during general anesthesia, the concentration of volatile substances in the tissues reaches a value sufficient for such interaction. Therefore, the selection of the dose of rocuronium bromide should be carried out by administering lower maintenance doses at longer intervals or using lower infusion rates of the drug during long (more than 1 hour) operations using inhalation anesthesia (see section "Interaction with other medicinal products").

Adult patients as a general rule in the conduct of endotracheal intubation and to ensure muscle relaxation in operations of varying duration,as well as when used in intensive care units, the following doses are recommended.

In surgical interventions

Endotracheal intubation

The standard dose of rocuronium bromide for endotracheal intubation is 0.6 mg / kg body weight, which after about 60 seconds in most patients provides acceptable conditions for intubation of the trachea. In the rapid sequential induction of anesthesia, the recommended dose is 1 mg / kg body weight. In this case, acceptable conditions for intubation of the trachea are achieved in all patients after 60 seconds. If a dose of 0.6 mg / kg of body weight is administered for rapid sequential induction of anesthesia, intubation of the trachea to the patient is recommended 90 seconds after the administration of rocuronium bromide.

Recommendations for the use of rocuronium bromide for rapid sequential induction of anesthesia in patients undergoing cesarean section are presented in the section on "Application during pregnancy and during breastfeeding".

High doses

If higher doses are necessary, it should be noted that, according to the results of clinical studies, the use of rocuronium bromide in a dose of up to 2 mg / kg did not result in an increase in the incidence or severity of cardiovascular adverse reactions.The introduction of such doses of rocuronium bromide reduces the time of onset of its action and increases its duration (see the section "Pharmacodynamics"). Maintenance doses

The recommended maintenance dose is 0.15 mg / kg body weight; with prolonged inhalation anesthesia, it should be reduced to 0.075-0.1 mg / kg. Supportive doses are best administered at the time when the degree of muscle contraction is restored to 25% of the original or when monitoring in the four-digit stimulation mode (TOF) there are 2-3 answers.

Continuous infusion

If rocuronium bromide injected through continuous infusion, it is recommended to give a loading dose equal to 0.6 mg rocuronium bromide per kg body weight, and when the neuromuscular conduction begins to recover, begin infusion. The rate of infusion should be selected in such a way that the contractile response of skeletal muscles is at the level of 10% of the initial or maintenance of 1-2 responses when monitoring in the four-digit stimulation mode (TOF). In adults with intravenous anesthesia, the infusion rate necessary to maintain muscle relaxation at this level is 0.3-0.6 mg / kg / h, and for inhalation anesthesia 0.3-0.4 mg / kg / h.It is necessary to constantly monitor neuromuscular conduction, as the required infusion rate can vary in different patients and with different methods of anesthesia.

Children

Doses recommended for intubation during routine anesthesia and maintenance,

in children 1-2 months, 3-23 months, 2-11 years, adolescents are similar to adults.

However, the duration of a single intubation dose in children 1-2 months

longer than in children of other age groups (see the section "Pharmacodynamics"),

With continuous infusion, its speed in children (excluding children 2-11 years old) is similar

adults. Children of 2-11 years may require a higher rate of administration.

Thus, the recommended initial infusion rate in children 2-11 years old is equal to that of

in adults, subsequently it is adjusted to maintain a contractile response to

level of 10% from the initial or 1-2 responses when monitoring in the four-digit

stimulation (TOF).

The experience with the use of rocuronium bromide in order to rapidly consecutive induction of anesthesia in children is limited. Therefore, the drug is not recommended to facilitate intubation of the trachea during the rapid sequential induction of anesthesia in children.

Elderly patients, patients with diseases of the liver and (or) bile duct and (or) with renal insufficiency

The standard dose for intubation of the trachea in elderly patients and patients with diseases of the liver and (or) bile ducts, as well as in the presence of kidney failure is 0.6 mg / kg body weight. When performing the rapid sequential induction procedure in patients with an expected prolonged duration of action of muscle relaxants, it is recommended to administer 0.6 mg / kg of rocuronium bromide. Regardless of the technique of administration, the recommended maintenance dose is 0.075-0.1 mg / kg body weight, the recommended infusion rate is 0.3-0.4 mg / kg / h (see also "Continuous Infusion").

Patients with overweight and obesity

When using the drug in patients with excessive body weight or obesity (such are considered patients whose body weight is 30% higher than ideal), the dose is reduced based on the ideal body weight.

Application in the intensive care unit

Intubation of the trachea

Doses are similar to those for surgical interventions.

Maintenance doses

The recommended loading dose is 0.6 mg / kg of body weight, followed by a transfer to a continuous infusion of the drug when restoring neuromuscular conduction to 10% from the initial or receiving 1-2 responses with stimulation in the mode TOF. In all cases, the dose is selected individually. The recommended initial rate of administration in order to maintain 80-90% of the muscle block (1 -2 responses at TOF-stimulation) in adult patients is 0.3-0.6 mg / kg / h for the first hour, after which, during the next 6-12 hours, the rate of administration is reduced according to the individual response. After that, individual needs remain relatively constant.

Based on the results of controlled clinical trials, a significant interindividual variation of the hourly infusion rate was identified, with an average value of 0.2-0.5 mg / kg / h depending on the nature and extent of organ disorders, concomitant treatment and individual patient characteristics. In order to ensure optimal control of each patient, it is highly recommended to carry out continuous monitoring of neuromuscular conduction.There are data on the use of rocuronium bromide lasting up to 7 days. Special patient groups

It is not recommended to use the drug to facilitate the implementation of artificial ventilation in intensive care units in children and elderly patients, due to the lack of safety and efficacy data in these patient groups.

Method of administration

Rokuronium bromide is administered intravenously in the form of a bolus injection or continuous infusion.

Compatibility studies were carried out with the following infusion liquids: rocuronium bromide in a concentration of 0.5 and 2 mg / ml is compatible with 0.9% sodium chloride solution, 5% dextrose solution, 5% dextrose solution in saline, sterile water for injection, Ringer's lactate and Hemacel. The introduction should begin immediately after mixing and complete within 24 hours. Unused solution is to be disposed of.

Since the drug does not contain a preservative, the solution should be used immediately after opening the vial.

After dilution with infusion liquids (see above), the drug remains chemically and physically stable for 72 hours at a temperature of 30 ° C.From a microbiological point of view, the diluted drug should be administered immediately. If the drug is not applied immediately, the patient / physician is responsible for the time and storage conditions prior to use, which usually should not exceed 24 hours at 2-8 ° C unless dilution is performed in controlled and validated aseptic conditions.

Side effects:

The most common adverse drug reactions are pain / reactions at the site of administration, changes in basic vital signs and an increase in the duration of the neuromuscular block. The most frequent serious undesirable drug reactions are anaphylactic and anaphylactoid reactions and associated symptoms. See also the table below.

System-Organ Class for MedDRA	Preferred term¹
System-Organ Class for MedDRA	Infrequently / rarely²(<1/100,> 1/10 LLC)	Very rarely (<1 / 10,000)
From the immune system		Hypersensitivity Anaphylactic reaction Anaphylactoid reaction Anaphylactic shock Anaphylactoid shock
From the nervous system		Flaccid paralysis
From the heart	Tachycardia
From the side of the vessels	Reduction of blood pressure	Collapse and shock "Tides" of blood
On the part of the respiratory, thoracic and mediastinal organs		Bronchospasm
From the skin and subcutaneous tissues		Angioedema Hives Rash Erythematous rash
System-Organ Class for MedDRA	Preferred term¹
System-Organ Class for MedDRA	Infrequently / rarely²(<1/100,> 1/10 LLC)	Very rarely (<1/10 LLC)
Musculoskeletal and connective tissue disorders		Muscle weakness³Steroid myopathy
General disorders and reactions at the site of administration	Ineffective drug Decreased drug effect / therapeutic response Increased drug effect / therapeutic response Pain at injection site Reaction at injection site	Edema of the face
Injuries, poisonings and procedural complications	Prolongation of neuromuscular blockade Deceleration of recovery from anesthesia	Respiratory complications after anesthesia

¹The frequency is based on post-registration observation and available literature data.

²Post-acquisition monitoring does not provide accurate estimates, therefore the frequency was divided into two, and not five, categories.

³After long-term use in the intensive care unit

Anaphylaxis

Very rarely, but reports of severe anaphylactic reactions in response to muscle relaxants, including rocuronium bromide. Anaphylactic / anaphylactoid reactions are manifested by bronchospasm, changes in the cardiovascular system (eg, lowering of arterial pressure, tachycardia, shock collapse) and changes in the skin (eg, angioedema, urticaria). In some cases, these reactions ended in a fatal outcome. Due to the potential severity of these reactions, it is always necessary to consider the possibility of their occurrence and to be ready.

Since it is known that muscle relaxants can cause local and systemic release of histamine, it is always necessary to take into account the possibility of itching and erythematous reactions at the site of administration and / or generalized histamine-like (anaphylactoid) reactions (see also the description above).

In clinical studies, after a rapid bolus injection of 0.3-0.9 mg / kg rocuronium bromide, only a slight increase in plasma histamine concentration was noted.

Prolongation of neuromuscular blockade

The most common undesirable reaction of muscle relaxants is an increase in the duration of their pharmacological action beyond the required period of time. The degree of this reaction can vary from the weakness of the skeletal muscles to the deep and prolonged paralysis of skeletal muscles, leading to respiratory failure or apnea.

Myopathy

After the application of various muscle relaxants in the intensive care unit in combination with glucocorticoids, myopathy was noted (see section "Special instructions").

Reactions at the site of administration

During rapid sequential induction of anesthesia, painful sensations were reported during injection, especially if the patient is still conscious, and especially when used as a means to induce anesthesia of propofol. In clinical trials, pain with injection was noted in 16% patients who underwent rapid sequential induction of anesthesia with propofol, and less than 0.5% of patients undergoing rapid sequential induction of anesthesia with fentanyl and thiopental sodium.

Children

Meta-analysis of 11 clinical trials in children (n = 704), in which rocuronium bromide (up to 1 mg / kg), showed that tachycardia occurred at a frequency of 1.4%.

Overdose:In case of an overdose, it is necessary to continue the artificial ventilation of the lungs and the administration of sedatives. There are two options for interrupting the neuromuscular blockade: (1) with reversible severe and deep blockade in adults, it is permissible to apply sugammadex. The dose of sugammadex depends on the degree of neuromuscular blockade. (2) With the onset of spontaneous respiration restoration, cholinesterase inhibitor (for example, neostigmine methyl sulfate, edrophonium chloride, pyridostigmine bromide) or sugammadex (at the required doses) may be administered. If the administration of the cholinesterase inhibitor does not remove the blocking effect of rocuronium bromide, ventilation is continued until self-respiration is restored. Multiple cholinesterase inhibitor administration can be dangerous.

In pre-clinical studies, severe cardiovascular depression did not occur until a total dose of 750xEDgo (135 mg / kg rocuronium bromide) was achieved.

Interaction:

It is shown that the following drugs affect the strength and (or) duration of action of nondepolarizing muscle relaxants.

The effect of other drugs on rocuronium bromide

Enhance the effect

- Inhaled anesthetics - halogenated hydrocarbons strengthen the neuromuscular block caused by the use of rocuronium bromide. This effect becomes noticeable with the administration of maintenance doses (see section "Method of administration and dose"). Restoration of neuromuscular conduction with cholinesterase inhibitors can be slowed down.

- Prior administration of suxamethonium (see section "Special instructions").

- - Prolonged concomitant administration of glucocorticosteroids and rocuronium bromide in

the intensive care unit may lead to an increase in the duration of neuromuscular blockade or to myopathy (see the sections "Side effects" and "Special instructions"). Other drugs:

- antibiotics: aminoglycosides, lincosamides and polypeptide antibiotics, acylaminopenicillin antibiotics;

- Diuretics, quinidine and its quinine isomer, magnesium salts, blockers of "slow" calcium channels, lithium salts, local anesthetics (lidocaine intravenously, bupivacaine epidural) and acute administration of phenytoin or (3-adrenoblockers.

Postoperative recovery was observed after the administration of aminoglycoside, lincosamide, polypeptide and acylaminopenicillin antibiotics, quinidine, quinine and magnesium salts.

Weakening the effect

- Previous long-term administration of phenytoin or carbamazepine.

- Calcium chloride, potassium chloride.

- Inhibitors of proteases (gabexate, vernastatin).

Different effect

- The introduction of other nondepolarizing muscle relaxants in combination with rocuronium bromide may cause a weakening or strengthening of the neuromuscular blockade, depending on the order of administration and the muscle relaxant used.

- When administered after rocuronium bromide, suxamethonium may lead to potentiation or weakening of the neuromuscular blockade caused by rocuronium bromide.

Effect of rocuronium bromide on other drugs

The combination of rocuronium bromide with lidocaine may lead to a faster onset

the latter.

Children

Formal studies of drug interactions were not conducted. When using rocuronium bromide in children, the above-mentioned interactions should be considered and appropriate precautions followed (see section "Special instructions"). Incompatibility

Determined that rocuronium bromide incompatible in one with a solution containing the following drugs: amphotericin B, amoxicillin, azathioprine, cefazolin, cloxacillin, dexamethasone, diazepam, enoximone, erythromycin, famotidine, furosemide, hydrocortisone sodium succinate, insulin, metohexital, methylprednisolone, prednisolone sodium succinate, sodium thiopental, trimethoprim and vancomycin.

Rokuronium bromide should not be mixed with other medicinal products, except those mentioned in the section "Method of administration and dose".

If rocuronium bromide it is proposed to introduce through the infusion system intended for administration of other drugs, it is necessary before and after the administration of rocuronium bromide to be properly rinsed (eg, 0.9% sodium chloride solution).

Special instructions:Because the rocuronium bromide causes paralysis of the respiratory muscles, patients receiving this drug are absolutely shown to have artificial ventilation of the lungs up to a satisfactory recovery of independent breathing. Like other muscle relaxants, it is necessary to foresee possible difficulties in intubation of the trachea, especially when the drug is used as part of a rapid sequential induction of anesthesia.

Like other muscle relaxants, after the application of rocuronium bromide, cases of development of the residual block were noted.To prevent complications resulting from the development of the residual block, it is recommended to extubate the trachea only after neuromuscular conduction has recovered sufficiently. Other factors that can cause the development of the residual block after extubation in the postoperative period (for example, drug interaction or the patient's condition) should also be considered. If this is not a standard practice, consideration should be given to the possibility of injecting drugs that repair neuromuscular conduction (sugammadex or cholinesterase inhibitors), especially in cases in which the occurrence of a residual block is most likely.

A high frequency of cross-sensitivity between muscle relaxants was reported. In this regard, if possible, before the introduction of rocuronium bromide, it is necessary to exclude hypersensitivity to other muscle relaxants. In sensitive patients rocuronium bromide should be used only on absolute indications. If the patient develops a hypersensitivity reaction during general anesthesia,in the subsequent they must be checked for hypersensitivity to other muscle relaxants.

Rokuronium bromide can increase the heart rate.

After prolonged use of muscle relaxants in intensive care units, continuous paralysis and / or weakness of skeletal muscles were noted. In order to prevent the possible prolongation of neuromuscular blockade and (or) overdose, it is necessary that during the entire period of the muscle relaxant application, the neuromuscular conduction is monitored, and that patients receive adequate anesthesia and sedatives. Furthermore, muscle relaxants should be administered in carefully selected doses in accordance with the patient's individual response, and the administration should be performed by an experienced physician familiar with or under the supervision of muscle relaxants, and using appropriate neuromuscular monitoring technology.

After prolonged administration of nondepolarizing muscle relaxants in combination with glucocorticosteroid therapy in the intensive care unit, the development of myopathy was regularly reported.In this regard, patients receiving both muscle relaxants and glucocorticosteroids, the period of administration of the muscle relaxant should be limited as much as possible.

If suksamethonium is used for intubation, the introduction of rocuronium bromide should be postponed until the clinical recovery of neuromuscular conduction, reduced due to administration of suxamethonium.

The following conditions may affect the pharmacokinetics and / or pharmacodynamics of rocuronium bromide

Diseases of the liver and (or) bile duct and (or) renal failure

Since rocuronium is excreted in the urine and bile, the drug should be used with caution in patients with clinically significant liver and (or) bile duct disease and / or renal insufficiency. In these groups of patients, prolongation of the effect with a dose of rocuronium bromide equal to 0.6 mg / kg of body weight was observed.

Increasing the circulation time

Factors that increase the circulation time of rocuronium bromide in the blood, such as cardiovascular diseases, elderly age and swelling, leading to an increase in the volume of distribution, may contribute to a later onset of action.Due to reduced clearance, the duration of action can also be reduced.

Neuromuscular diseases

Like other muscle relaxants, rocuronium bromide should be used with extreme caution in patients with neuromuscular diseases or having suffered poliomyelitis, since the reaction to muscle relaxants in these cases can be highly distorted. The magnitude and nature of these changes can be very different. In patients with severe myasthenia gravis or myasthenic syndrome (Eaton-Lambert syndrome), small doses of rocuronium bromide can cause severe neuromuscular blockade, so the selection of an effective dose should be based on the answer. Hypothermia

When conducting surgical interventions against hypothermia, the miorelaxing effect of rocuronium bromide is enhanced, and the duration of action is increased.

Obesity

Like other muscle relaxants, patients with obesity rocuronium bromide may have a longer effect, and spontaneous recovery of the normal state of neuromuscular conduction after its application may be longer.

Burns

In patients with burns, resistance to non-depolarizing muscle relaxants may develop.The selection of the effective dose should be based on the answer.

States that can enhance the effect of rocuronium bromide

Hypokalemia (eg, after severe vomiting, diarrhea or diuretic treatment), hypermagnesia, hypocalcemia (after massive blood transfusions), hypoproteinemia, dehydration, acidosis, hypercapnia, cachexia.

In this regard, severe electrolyte imbalance, changes in blood pH or dehydration should, if possible, be corrected.

Effect on the ability to drive transp. cf. and fur:Because the rocuronium bromide are used as an aid in general anesthesia, the usual precautionary measures recommended after general anesthesia for outpatients should be followed. It is not recommended to manage potentially dangerous mechanisms or drive a car within 24 hours after the complete recovery of neuromuscular conduction caused by rocuronium bromide.

Form release / dosage:

Solution for intravenous administration 10 mg / ml (50 mg / 5 ml, 100 mg / 10 ml).

Packaging:

5 ml or 10 ml in bottles of colorless, neutral glass, hermetically sealed with rubber stoppers, with aluminum or aluminum-plastic caps with control of the first opening.

For 1 or 5, or 10, or 12 bottles of 5 ml or 10 ml, together with the instructions for use are placed in a pack of cardboard with partitions or special cardboard nests (for hospitals). 20. 50 or 100 vials (5 ml or 10 ml each) with an equal number of instructions for use are placed in a cardboard box (for hospitals).

Storage conditions:At a temperature of no higher than 8 ° C in a dark place. Do not freeze. Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:For hospitals

Registration number:LP-002701

Date of registration:10.11.2014/22.06.2015

Date of cancellation:2019-11-10

The owner of the registration certificate:LENS-PHARM, LLC LENS-PHARM, LLC Russia

Manufacturer: & nbsp

LENS-PHARM, LLC Russia

Information update date: & nbsp12.06.2016

Illustrated instructions

Instructions

Croaron (Kruaron)