Ridelat-S solution 10mg/ml 5ml ampoules, 10pcs

Composition

1 ampoule (5 ml) contains: Active ingredient: atracurium bezylate 50 mg; excipients: benzenesulfonic acid-up to pH 3.0-3.8, water for injection-up to 5 ml

Pharmacological action

Pharmacotherapeutic group: non-depolarizing muscle relaxant of peripheral action

ATX code: M 03 AC 04

Pharmacological properties

Mechanism of action

Atracurium bezylate is a highly selective non-depolarizing muscle relaxant of a competitive type of action. Atracurium bezylate reduces the sensitivity of N-cholinergic receptors in the synaptic region to acetylcholine, which makes it impossible to excite the muscle fiber and its contraction. Promotes the release of histamine.

Pharmacodynamic effects

Atracurium bezylate has no direct effect on intraocular pressure. Thus, atracurium bezilate is applicable in ophthalmic surgical practice.

Pharmacokinetics

Metabolism

Atracurium bezylate is inactivated by Hofmann elimination (a process that occurs at physiological pH and temperature values without the involvement of enzymes) and by ether hydrolysis with the participation of non-specific esterases. Plasma studies in patients with low pseudocholinesterase levels have shown that the metabolic products of atracurium bezylate do not change. Changes in blood pH and body temperature within physiological limits do not significantly affect the duration of action of atracurium bezilate.

Deduction

The duration of neuromuscular blockage caused by use of atracurium bezylate does not depend on its metabolism in the liver or kidneys or excretion. Therefore, it is unlikely that the duration of action of the drug changes with impaired kidney, liver or circulatory disorders.

Special patient groups

Hemofiltration and hemodiafiltration have minimal effect on the plasma concentrations of atracurium bezilate and its metabolites (including laudanosine). The effect of hemodialysis and hemoperfusion on the plasma concentrations of atracurium bezylate and its metabolites is unknown. Higher concentrations of atracurium bezilate metabolites were observed in intensive care unit patients with impaired renal and/or hepatic function. The metabolites do not affect neuromuscular conduction.

Indications

As a component of general anesthesia to provide tracheal intubation and relaxation of skeletal muscles during surgical procedures, or controlled ventilation, and to facilitate artificial ventilation (IVL) in patients in intensive care units (ICU).

Use during pregnancy and lactation

FertilityThe effect on fertility has not been studied.

PregnancyAnimal studies have shown that the use of atracurium bezylate does not significantly affect fetal development. Like other muscle relaxants, Ridelat® – C should be used during pregnancy only when the potential benefit to the mother outweighs any possible risk to the fetus. Ridelat® – C can be used with the muscle relaxation chain during cesarean section, since atracurium bezilate does not cross the placental barrier in clinically significant amounts when prescribed at the recommended doses.

Breast-feeding periodThere are no data on the penetration of atracurium bezylate into breast milk.

Contraindications

• hypersensitivity to atracurium, cisatracurium or benzenesulfonic acid, any other components of the drug;
• known hypersensitivity to histamine.

Side effects

The adverse reactions listed below are listed according to the incidence of organ damage and organ systems. The frequency of occurrence is determined as follows:  very common (≥1/10), common (≥1/100 and <1/10), infrequent (≥1/1000 and <1/100), rare (≥1/10000 and <1/1000), very rare ( Frequency categories:  very often, often and infrequently were formed on the basis of clinical studies of atracurium bezilate. The frequency categories rarely and very rarely were formed based on spontaneous messages.

Data from clinical trials

Vascular disorders:  often-a decrease in blood pressure (mild, transient), hyperemia of the skin.

Respiratory, thoracic and mediastinal disorders:  infrequently-bronchospasm. Post-marketing surveillance data

Immune system disorders:  very rarely – anaphylactic and anaphylactoid reactions, including shock, circulatory failure and cardiac arrest. Very rarely, severe anaphylactic or anaphylactoid reactions have been reported in patients taking atracurium bezilate in combination with one or more anesthetics.

Nervous system disorders:  unknown – convulsions. Seizures have been reported in ICU patients treated with atracurium bezilate in combination with certain other medications. Usually, these patients experienced one or more conditions predisposing to seizures, such as head trauma, cerebral edema, viral encephalitis, hypoxic encephalopathy, and uremia. A causal relationship between seizures and laudanosine has not been established. As a result of clinical studies, there is no correlation between plasma concentrations of laudanosine and the occurrence of seizures.

Skin and subcutaneous tissue disorders:  rarely – urticaria.

Musculoskeletal and connective tissue disorders:  unknown – myopathy, muscle weakness. Several cases of muscle weakness and/or myopathy have been reported with prolonged use of muscle relaxants in critically ill ICU patients. Most of them received concomitant glucocorticosteroids. These adverse reactions were rare, and a causal relationship with the use of atracurium bezilate has not been established

Interaction

Neuromuscular blockage induced by atracurium bezilate may increase with the use of inhaled anesthesia.

As with other non-depolarizing muscle relaxants, it is possible to increase the intensity and / or duration of neuromuscular blockade as a result of interaction with the following drugs: – antibiotics, including aminoglycosides, polymyxins, spectinomycin, tetracyclines, lincomycin and clindamycin; – antiarrhythmics: propranolol, calcium channel blockers, lidocaine, procainamide and quinidine; – diuretics: furosemide and possibly mannitol, thiazide diuretics and acetazolamide;- magnesium sulfate;- ketamine; – lithium salts; – ganglioblockers: trimetaphane, hexamethonium.

In rare cases, certain drugs cause an exacerbation of myasthenia gravis, contribute to the development of latent myasthenia gravis, as well as myasthenic syndrome, in which it is possible to increase sensitivity to atracurium bezilate. These drugs include various antibiotics, beta-blockers (propranolol, oxprenolol), antiarrhythmic (procainamide, quinidine) and antirheumatic drugs (chloroquine, D-penicillamine), trimetafan, chlorpromazine, steroids, phenytoin and lithium salts.

The development of neuromuscular blockade caused by non-depolarizing muscle relaxants is likely to slow down, and its duration decreases in patients receiving anticonvulsant therapy for a long time. The combined use of non-depolarizing neuromuscular conduction blockers and atracurium bezilate may cause excessive blockade compared to the expected use of one atracurium bezilate in an equipotential total dose. Any synergistic effect may vary with different drug combinations. The depolarizing muscle relaxant suxamethonium chloride should not be used to prolong neuromuscular blockade caused by non-depolarizing muscle relaxants such as atracurium bezilate, as this can cause prolonged and complex blockade that is difficult to stop with anticholinesterase agents.

Therapy with anticholinesterase drugs often used to treat Alzheimer’s disease, such as donepezil, may shorten the duration of neuromuscular blockage and weaken the blocking effect of atracurium bezilate.

Pharmaceutical compatibilityDrug Radelat®is compatible with the following solutions for infusion (at a concentration of 0.5-0.9 mg/ml in daylight and temperatures up to +30 °C) solution of sodium chloride 0.9% for the on/in the introduction – for at least 24 h,5% dextrose solution for the on/in the introduction – 8 h, ringer solution for injection,8 h, a solution of sodium chloride 0.18% and dextrose 4% for/in the introduction – 8 hours Hartman’s solution for the on/in the introduction – 4 hours

How to take it, course of use and dosage

The table of pharmaceutical compatibility of the drug Ridelat® – C with certain infusion solutions is given in the section Interaction with other medicinal products.

Adults

Injectable use in adults

Ridelat® – C is administered intravenously as an injection. For adults, the dose range of Ridelat® – C is 0.3-0.6 mg / kg (depending on the required duration of complete blockade), which provides adequate myoplegia for 15-35 minutes.

After intravenous use at doses of 0.5-0.6 mg/kg, endotracheal intubation can usually be performed after 90 seconds.

If it is necessary to prolong the complete neuromuscular blockade, Ridelat®-C is additionally administered at a dose of 0.1-0.2 mg/kg.

Proper use of additional doses of the drug does not lead to accumulation of the muscle relaxant effect.

Spontaneous recovery of conduction after complete neuromuscular blockade occurs in approximately 35 minutes, which is determined by the restoration of tetanic contraction to 95% of normal neuromuscular function.

Neuromuscular blockage caused by atracurium can be quickly eliminated by the use of anticholinesterase agents in standard doses, such as neostigmine and edrophonium. in combination with simultaneous or preliminary use of atropine (without signs of recurarization).

Infusion use in adults

After an initial bolus dose of 0.3-0.6 mg/kg, Ridelate® – C can be used to maintain neuromuscular blockade during prolonged surgical intervention by continuous infusion at a rate of 0.3-0.6 mg / kg / h.

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

Children

Children aged 2 years and older Ridelat® – C is prescribed in the same doses as adults, in terms of body weight.

The initial dose of Ridelat® – C, used in children aged 1 month to 2 years with halothane anesthesia, is 0.3-0.4 mg/kg. Children may need more frequent maintenance doses than adults.

Elderly patients

Ridelat® – C can be used in standard doses in elderly patients. However, it is recommended to use an initial dose that is less than the lower value of the dose range, and to administer the drug slowly.

Use in patients with impaired renal and/or hepatic function

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

Use in patients with cardiovascular diseases

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

Use in ICU patients

After use, if necessary, of Ridelat®-C in an initial bolus dose of 0.3-0.6 mg/kg, the drug can be used to maintain neuromuscular blockade by prolonged infusion at a rate of 11-13 mcg / kg / min (0.65-0.78 mg / kg / h). However, there are wide inter-individual differences in the dosage regimen. The dosage regimen may vary over time. Some patients may require either a low infusion rate of 4.5 mcg/kg/min (0.27 mg/kg/h) or a high infusion rate of 29.5 mcg/kg/min (1.77 mg/kg/h).

The rate of spontaneous recovery from neuromuscular blockage at the end of Ridelat®-C infusion in ICU patients does not depend on the duration of use. Spontaneous recovery of neuromuscular conduction (the ratio of quarter height to first twitch in the train-of-four test T4/T1 >0.75) usually occurs after approximately 60 minutes. In clinical studies, this period ranged from 32 to 108 minutes after atracurium bezilate infusion, and its rate does not depend on the duration of drug use.

Breeding instructions

Ridelat® – C is compatible with the following infusion solutions:

Ridelat®-C solution, when diluted with compatible infusion solutions to obtain a concentration of atracurium bezylate of at least 0.5 mg / ml, remains stable for a specified period of time under normal lighting at temperatures up to 30 °C.

Overdose

Symptoms: prolonged muscle paralysis and its consequences.

Treatment: Ventilator under positive pressure until spontaneous respiration is restored. It is necessary to use sedatives, since the consciousness of patients is not disturbed.

As soon as there are signs of spontaneous recovery, it can be accelerated with anticholinesterase drugs in combination with atropine or glycopyrrolate.

Description

clear or almost transparent solution from colorless to light yellow.

Special instructions

Like other muscle relaxants, atracurium bezilate causes paralysis of the respiratory muscles, as well as skeletal muscles, but does not affect consciousness. Ridelat® – C should only be administered under general anesthesia under the close supervision of a qualified anesthesiologist, with equipment for tracheal intubation and mechanical ventilation.

In predisposed patients, atracurium bezilate may cause histamine release reactions. Caution should be exercised when administering Ridelat®-C to patients with a history of hypersensitivity to the effects of histamine. In particular, bronchospasm may occur in patients with a history of allergies or bronchial asthma. Caution is also required when administering Ridelat® – C to patients who have experienced hypersensitivity reactions to other muscle relaxants, as there is a high frequency of cross-sensitivity between muscle relaxants (more than 50%) (see fig. Contraindications).

For patients with asthma who are receiving high-dose corticosteroids and muscle relaxants in the intensive care unit, repeated monitoring of creatine phosphate kinase (CPK) levels should be considered. When used in the recommended dose range, atracurium bezilate does not cause significant blockage of the vagus nerve and nerve ganglia. Therefore, atracurium bezilate in the recommended dose range does not have a clinically significant effect on heart rate and does not prevent bradycardia caused by many anesthetics or vagus nerve stimulation during surgery.

As with other non-depolarizing muscle relaxants, hypophosphatemia may slow recovery. Recovery can be accelerated by correcting this condition.

As with other muscle relaxants, severe disturbances in the acid-base balance and / or disturbances in the balance of serum electrolytes may increase or decrease the sensitivity of patients to Ridelat-C.

As with other non-depolarizing muscle relaxants, hypersensitivity to atracurium bezilate may occur in patients with severe myasthenia gravis, other neuromuscular diseases, and severe electrolyte disturbances.

Patients with a tendency to a sharp decrease in blood pressure, for example, with hypovolemia, Ridelat® – C is recommended to be administered for more than 60 seconds.

Atracurium bezylate is inactivated in an alkaline environment, and therefore Ridelate® – C should not be mixed in the same syringe with thiopental or any alkaline solutions.

If the drug Ridelat® – C is administered into a small-caliber vein, then after the injection it should be washed with saline solution. When other anesthetics are administered through the same injection needle or cannula, it is important that each drug is washed off with the appropriate amount of saline solution.

The solution of the drug Ridelat® – C is hypotonic, and it cannot be administered simultaneously through the same system with blood transfusion. Studies of malignant hyperthermia in predisposed animals (pigs) and clinical studies in patients sensitive to malignant hyperthermia show that atracurium bezilate does not cause this syndrome.

As with other non-depolarizing muscle relaxants, patients with burns may develop resistance when prescribed Ridelat® – C. In such cases, it may be necessary to increase the doses, the amount of which depends on the time elapsed after the burn, and on the surface area of the burn.

ICU patients: High-dose use of laudanosine, a metabolite of atracurium bezilate, to laboratory animals has been associated with a transient reduction in blood pressure, and in some animal species with cerebral excitatory effects.

Convulsions have been reported in patients in the intensive care unit treated with atracurium bezilate, but a causal relationship with laudanosine (a metabolite of atracurium bezilate) has not been established (see Side effect).

Form of production

Solution for intravenous use of 10 mg / ml. 5 ml in ampoules of colorless neutral glass with a colored break ring or with a colored dot and notch. The ampoules are additionally marked with one, two or three colored rings and/or a two-dimensional barcode, and/or alphanumeric encoding, or without additional colored rings, a two-dimensional barcode, or alphanumeric encoding. 5 ampoules each in a contour cell package made of polyvinyl chloride film and aluminum foil, or transparent polymer film, or without aluminum foil and polymer film.1 or 2 contour cell packages together with instructions for use in a cardboard pack. In the case of drug production at OOO “DEKO COMPANY”.5 ml in ampoules of colorless neutral glass with a colored break ring or with a colored dot and notch. The ampoules are additionally marked with one, two or three colored rings and/or a two-dimensional barcode, and/or alphanumeric encoding, or without additional colored rings, a two-dimensional barcode, or alphanumeric encoding. 5 or 10 ampoules in a contour cell package made of polyvinyl chloride film and aluminum foil, or transparent polymer film, or without aluminum foil and polymer film. 1 contour cell pack together with instructions for use in a cardboard pack.

Storage conditions

In a dark place at a temperature of 2 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

Atrakuriya bezilat

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection