Bridan solution 100mg/ml 2ml vials, 10pcs

Composition

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1 ml of solution for intravenous use contains: Active ingredient:  

sugammadex 100 mg,

excipients:  

hydrochloric acid and / or sodium hydroxide,

water for injection

Pharmacological action

Braidan is a selective antidote for muscle relaxants. Sugammadex is a modified gamma-cyclodextrin, which is a drug that selectively binds muscle relaxants. It forms a complex with the muscle relaxants rocuronium bromide and vecuronium bromide in the blood plasma, as a result, the number of muscle relaxant molecules binding to n-holinoreceptors in the neuromuscular junction decreases. This leads to the elimination of neuromuscular blockade caused by rocuronium bromide and vecuronium bromide.

There was a clear dependence of the effect on the dose of sugammadex, which was administered at different time periods and at different depths of neuromuscular conduction blockade. Sugammadex was administered in doses from 0.5 to 16 mg / kg both after a single use of rocuronium bromide at doses of 0.6,0.9,1 and 1.2 mg/kg, or after the introduction of vecuronium bromide at a dose of 0.1 mg / kg, and after the introduction of maintenance doses of these muscle relaxants.

Sugammadex can be used at various times after the introduction of rocuronium bromide or vecuronium bromide.

Pharmacokinetics

The pharmacokinetic parameters of sugammadex were calculated based on the summation of the concentrations of free sugammadex and sugammadex in the sugammadex-muscle relaxant complex. Pharmacokinetic parameters, such as clearance and_{vd, are considered the}same for sugammadex, which is outside the complex, and sugammadex, which is part of the complex with a muscle relaxant.

With bolus use of sugammadex in doses from 1 to 16 mg/kg, its pharmacokinetics are linear.

Pharmacokinetic parameters of sugammadex after intravenous use in adult patients: fast phase of distribution with a half-life of 2.9 min; slow phase of distribution with a half-life of 27 min; V_ss – 11-14 l, clearance – 88 ml/min.

Distribution

After intravenous use of sugammadex to adult patients, the rapid phase of distribution with a half-life of 2.9 minutes; the slow phase of distribution with a half-life of 27 minutes; T_1/2 – 1.8 h, V_ss-11-14 l, clearance-88 ml/min. Neither sugammadex nor the sugammadex-rocuronium complex binds to plasma proteins or red blood cells.

Metabolism

To date, no metabolites of sugammadex have been detected.

Deduction

Sugammadex is excreted unchanged by the kidneys. T_1/2 of sugammadex is 1.8 h, and plasma clearance is 88 ml/min.

More than 90% of the dose is eliminated within 24 hours. 96% of the dose is excreted in the urine, of which 95% is unchanged sugammadex. Less than 0.02% of sugammadex is excreted in the faeces and exhaled air.

Pharmacokinetics in special clinical cases

Elderly patients with impaired renal function

Pharmacokinetic parameters in elderly patients (Table 1) with varying degrees of impaired renal function, which was measured by the value of creatinine clearance, were evaluated based on a population pharmacokinetic analysis.

Table 1. Pharmacokinetic parameters of sugammadex in elderly patients (body weight 75 kg) with impaired renal function.

In children and adolescents under 18 years of_{age, vss} and clearance increase with age. The variability of plasma concentrations of sugammadex in children is comparable to that in adults.

Table 2. Pharmacokinetic parameters in two typical paediatric patients.

There were no clinically significant differences in pharmacokinetic parameters depending on gender, race, and body weight.

Indications

• Elimination of neuromuscular blockade caused by rocuronium bromide or vecuronium bromide;
• elimination of neuromuscular blockade caused by rocuronium bromide in children from 2 years of age and adolescents in standard clinical situations.

Use during pregnancy and lactation

The use of the drug is contraindicated Braidan during pregnancy due to insufficient data.

It is not known whether sugammadex is excreted in human breast milk, but based on data from preclinical studies, the possibility of this is not excluded. The absorption of cyclodextrins by oral use is low and has no effect on the children after use of a bolus dose of sugammadex to a nursing mother. However, apply the drug Braidan in women during breastfeeding should not be used.

The use of the drug is contraindicated Braydan for children under 2 years old.

Contraindications

• severe renal insufficiency (creatinine clearance < 30 ml / min);
• severe hepatic insufficiency;
• hypersensitivity to the components of the drug.

Side effects

Allergic reactions:  rarely (≥1/1000 to Several people experienced allergic reactions after taking sugammadex. As a rule, these cases regressed independently, and additional therapy was not required.

Complications during anesthesia:  frequently (≥ 1/100) (association with sugammadex use was considered unlikely).2% (the frequency was estimated by monitoring neuromuscular conduction) – repeated development of blockade after the use of sugammadex at a suboptimal dose (less than 2 mg / kg).

From the digestive system:  very often (≥ 1/10 in volunteers) – dysgeusia (metallic or bitter taste) after the use of sugammadex at a dose of 32 mg / kg or higher.

Respiratory system disorders:  patients with a history of lung complications are at risk of developing bronchospasm.

Interaction

Interaction by binding type

With the introduction of sugammadex, the effectiveness of certain medications may decrease due to a decrease in their plasma (free) concentration. In such a situation, it is necessary to either re-administer the drug or prescribe a therapeutically equivalent drug (preferably of a different chemical class).

Interaction by displacement type

With the introduction of certain medications after the use of sugammadex, theoretically rocuronium and vecuronium can be displaced from the complex with sugammadex, as a result of which the neuromuscular blockade may resume. In such cases, it is necessary to start using the ventilator again.

Infusion of the drug that resulted in the displacement of rocuronium or vecuronium from the complex with sugammadex should be discontinued. If a displacement-type interaction is expected to develop after parenteral use of another drug (which was made within 6 hours after the use of sugammadex), then the level of neuromuscular conduction should be constantly monitored for signs of the development of repeated blockade.

Interaction by type of displacement is possible after the introduction of the following drugs: toremifene, flucloxacillin and fusidic acid.

Clinically significant pharmacodynamic interactions with other medicinal products can be expected:

– for toremifene, flucloxacillin and fusidic acid, the possibility of interaction by type of displacement is not excluded (clinically significant interaction by type of binding is not expected);

– for hormonal contraceptives, the possibility of interaction by type of binding is not excluded (clinically significant interaction by type of displacement is not expected).

Interactions that potentially affect the effectiveness of sugammadex

Toremifene, which has a relatively high binding constant and relatively high plasma concentrations, is able to displace vecuronium or rocuronium to some extent from the complex with sugammadex. Therefore, recovery of the T4/T1 ratio to 0.9 may be delayed in patients who received toremifen on the day of surgery.

Intravenous use of flucloxacillin at a high dose (infusion of more than 500 mg) may lead to some displacement of rocuronium or vecuronium from the complex with sugammadex.

The use of high-dose flucloxacillin in the preoperative period may lead to a slight delay in restoring the T%^%4/T%^%1 ratio to 0.9. High-dose flucloxacillin should be avoided in the postoperative period for 6 hours.If you need to administer flucloxacillin during this time period, you should carefully monitor the state of neuromuscular conduction and breathing, especially during the first 15 minutes after use of this drug.

Interactions that potentially affect the effectiveness of other drugs

The interaction between sugammadex at a dose of 4 mg / kg and progesterone can lead to a decrease in progestogen exposure (34% AUC), which is similar to the situation observed when skipping a daily dose of oral contraceptive. Therefore, the use of a bolus dose of sugammadex is considered equivalent to one missed daily dose of steroid oral contraceptives (combined or containing only progestogen).

If an oral contraceptive was taken on the day of taking sugammadex, you should refer to the section of the instructions for use of oral contraceptives that describes actions when skipping a dose.

In the case of using hormonal contraceptives that have a different method of use than oral, the patient should use an additional non-hormonal contraceptive method for the next 7 days and consult the instructions for use of this contraceptive for information.

Impact on laboratory parameters

In general, sugammadex does not affect laboratory tests, with the possible exception of the test for the quantitative determination of progesterone in blood serum.

Pharmaceutical incompatibilities

Braidan should not be mixed with other drugs and solutions, except for those intended for its dilution.

Sugammadex is physically incompatible with verapamil, ondansetron and ranitidine.

How to take, course of use and dosage

Braidan is only used by or under the supervision of an anesthesiologist. To monitor the degree of neuromuscular blockage and recovery of neuromuscular conduction, it is recommended to use an appropriate monitoring method.

It is generally recommended that neuromuscular conduction be monitored in the postoperative period to detect adverse events, including recurrent blockage. If drugs that may lead to displacement-type interactions with sugammadex are administered parenterally within 6 hours after sugammadex use, neuromuscular conduction should be monitored for signs of repeated blockage.

The recommended dose of sugammadex depends on the degree of neuromuscular blockage that needs to be eliminated.

The recommended dose does not depend on the type of anesthesia.

Adults

Braidan is used to eliminate the blockage of neuromuscular conduction of various depths caused by rocuronium bromide or vecuronium bromide.

Elimination of neuromuscular blockage in standard clinical situations (residual blockage of neuromuscular conduction)

Braidan at a dose of 4 mg / kg is recommended to be administered when the recovery of neuromuscular conduction has reached the level of 1-2 post-tetanic contractions (in the post-tetanic counting mode, PTS) after a blockade caused by rocuronium bromide or vecuronium bromide. The average time to complete recovery of neuromuscular conduction (T4/T1 ratio to 0.9) is approximately 3 minutes.

Braidan at a dose of 2 mg / kg is recommended to be administered when spontaneous recovery of neuromuscular conduction after blockade caused by rocuronium bromide or vecuronium bromide has reached at least 2 responses in the four-digit stimulation (TOF) mode. The average time to restore the T4/T1 ratio to 0.9 is about 2 minutes.

When using sugammadex at the recommended doses to restore neuromuscular conduction in standard clinical situations, a faster recovery of the T4/T1 ratio to 0.9 occurs when neuromuscular blockade is caused by rocuronium bromide, compared with vecuronium bromide.

Emergency elimination of neuromuscular blockade caused by rocuronium bromide

If there is a need for immediate restoration of neuromuscular conduction in a block caused by rocuronium bromide, the recommended dose of sugammadex is 16 mg/kg.

When sugammadex was administered at a dose of 16.0 mg / kg 3 minutes after the use of a bolus dose of 1.2 mg / kg of rocuronium bromide, the average time to restore the T4/T1 ratio to 0.9 is about 1.5 minutes.

Repeated use of sugammadex

In exceptional cases of postoperative recurarization, after use of sugammadex at a dose of 2 mg / kg or 4 mg / kg, the recommended repeated dose of sugammadex is 4 mg/kg. After repeated use of sugammadex, neuromuscular conduction should be monitored until neuromuscular function is fully restored.

Repeated use of rocuronium bromide or vecuronium bromide after use of sugammadex

after 24 hours.

Use of the drug in special groups of patients

In patients with mild to moderate renal impairment (creatinine clearance 30-80 ml / min), the drug should be used at the recommended doses for adult patients without renal pathology.

It is not recommended to use sugammadex in patients with severe renal impairment, including patients who are on program hemodialysis.

After the introduction of sugammadex in the presence of 2 responses in the mode of TOF stimulation against the background of blockade caused by rocuronium bromide, the total recovery time of neuromuscular conduction (T4/T1 ratio up to 0.9) in adult patients (18-64 years) is on average 2.2 minutes, in elderly patients (65-74 years) – 2.6 minutes, in senile patients (75 years and more) – 3.6 minutes. Despite the fact that the recovery time of neuromuscular conduction in elderly patients is somewhat longer, it is recommended to use sugammadex in doses intended for adult patients of the middle age group.

In obese patients, the dose of sugammadex should be calculated based on actual body weight. In this category of patients, the drug is recommended to be used in doses intended for adult patients.

In patients with impaired liver function, the recommended dosage remains the same as in adult patients, since sugammadex is mainly excreted by the kidneys. Due to insufficient data on the use of sugammadex in patients with severe hepatic impairment, Braidan should be used with extreme caution in these conditions.

Children

Data on the use of sugammadex in children are limited. It is possible to administer the drug to eliminate neuromuscular blockade caused by rocuronium bromide, if 2 responses appear in the TOF stimulation mode.

To eliminate neuromuscular blockade caused by rocuronium bromide, in daily practice in children and adolescents aged 2 to 17 years, it is recommended to administer sugammadex at a dose of 2 mg / kg (if there are 2 responses in the TOF stimulation mode).

Other situations of neuromuscular conduction restoration that occur in standard practice have not been studied, so it is not recommended to use sugammadex in these cases until further data are obtained.

Emergency restoration of neuromuscular conduction with the introduction of sugammadex in children from 2 years of age and adolescents has not been studied, and therefore in these situations, the use of the drug is not recommended until further data are obtained.

The drug can be diluted to improve the accuracy of dosing in children.

Rules for using the drug

Braidan is administered intravenously as a single bolus injection for 10 seconds directly into a vein or into the system for intravenous infusions.

When sugammadex is administered via a single infusion system with other medications, it is necessary to thoroughly flush the system (for example,0.9% sodium chloride solution) between the use of Braidan and drugs that are incompatible with it, as well as if compatibility is not established.

Sugammadex can be administered in one system for intravenous infusion along with the following infusion solutions: 0.9% (9 mg/ml) sodium chloride solution; 5% (50 mg/ml) glucose solution; 0.45% (4.5 mg/ml) sodium chloride solution with 2.5% (25 mg/ml) glucose; Ringer’s solution with lactic acid; Ringer’s solution; 5% (50 mg/ml) glucose solution in 0.9% (9 mg/ml) sodium chloride solution.

For use in children, Braidan can be diluted with 0.9% (9 mg/ml) sodium chloride solution to a concentration of 10 mg / ml.

Overdose

So far, one report has been received of an accidental overdose of the drug at a dose of 40 mg / kg. There were no significant side effects.

Sugammadex is well tolerated at doses up to 96 mg / kg, and there are no dose-related or non-dose-related side effects.

Data obtained in a limited number of patients with impaired renal function and undergoing programmed hemodialysis indicate an unstable decrease in the plasma level of sugammadex due to hemodialysis.

Special instructions

It is necessary to perform mechanical ventilation until adequate independent breathing is fully restored after the elimination of neuromuscular blockade. Even if neuromuscular conduction is fully restored, other medications that were used during the peri-and postoperative periods can inhibit respiratory function and therefore prolonged mechanical ventilation may be required.

If neuromuscular block develops again after extubation, adequate mechanical ventilation should be provided in time.

Repeated development of neuromuscular blockade was observed mainly in cases when the drug was administered in suboptimal (insufficient) doses. In order to prevent the recurrence of neuromuscular blockade, the drug should not be used in doses lower than recommended.

Repeated use of rocuronium bromide or vecuronium bromide after the use of sugammadex is possible after 24 hours.

If there is a need for neuromuscular blockade before the expiration of this time (24 hours), then nonsteroidal muscle relaxants should be used.

In patients with severe renal impairment (CC Data obtained in a limited number of patients with impaired renal function and undergoing programmed hemodialysis indicate an unstable decrease in the plasma level of sugammadex due to hemodialysis. The use of sugammadex in patients with severe renal impairment is not recommended.

When using rocuronium bromide or vecuronium bromide, you should take into account information from the instructions for medical use about drugs that potentiate neuromuscular blockade. If neuromuscular blockage is repeated, mechanical ventilation and repeated use of sugammadex may be required.

When neuromuscular conduction was restored intentionally during anesthesia, there were rare signs of surface anesthesia (movement, coughing, grimacing).

If neuromuscular blockage is removed during anesthesia, additional doses of anesthetics and/or opioid analgesics may be required.

Sugammadex is not metabolized in the liver, so studies in patients with impaired liver function have not been conducted. When using the drug in patients with severe hepatic impairment, special caution is required.

The use of sugammadex in patients treated with rocuronium bromide or vecuronium bromide in the ICU has not been studied.

Sugammadex is not used to eliminate the blockade of neuromuscular conduction caused by such muscle relaxants as suxamethonium or benzylisoquinoline compounds.

Sugammadex is not used to eliminate neuromuscular blockage caused by other steroid muscle relaxants, since there are no data on the effectiveness and safety of such use. There are only limited data on the elimination of neuromuscular conduction blockade caused by pancuronium, but their insufficient number does not allow us to recommend sugammadex for restoring neuromuscular conduction in the case of using this muscle relaxant.

In conditions associated with prolonged circulation time of the Active ingredient (cardiovascular diseases, elderly age, renal and hepatic insufficiency), the recovery time of neuromuscular conduction may increase.

When the drug is administered, there is a risk of developing allergic reactions, which may require emergency therapy.

When using the drug in patients on a diet with controlled sodium intake, it should be taken into account that 1 ml of the solution contains 9.7 mg of sodium. A sodium dose of 23 mg can be considered as sodium-free. If you need to enter more than 2.4 ml of the solution, then this should be considered in patients on a diet with limited sodium intake.

Studies have shown that sugammadex, either alone or in combination with rocuronium bromide or vecuronium bromide, does not cause prolongation of the QT interval.

During anesthesia, various combinations of medications are often administered that can prolong the QTc interval (for example, sevoflurane or propofol). In such cases, the usual precautions should be taken to prevent the development of arrhythmia.

In vitro experimental studies revealed a pharmacodynamic interaction (increased APTT and prothrombin time) of sugammadex with vitamin K antagonists, unfractionated heparin, low-molecular-weight heparins, rivaroxaban, and dabigatran. In studies on volunteers, the increase in these indicators was short-term (up to 30 minutes).

Currently, no clinically significant effect of sugammadex (in the form of ionotherapy or in combination with these anticoagulants) on the frequency of peri – or postoperative bleeding has been identified.

Taking into account the short-term nature of the increase in APTT and prothrombin time caused by sugammadex (as monotherapy or in combination with the above coagulants), it is unlikely that sugammadex increases the risk of bleeding.

Since there is currently no information on the use of sugammadex in patients with coagulopathies, in such cases it is necessary to carefully monitor the coagulation parameters in accordance with standard clinical practice.

After dilution of sugammadex with infusion solutions, the physical and chemical stability of the drug is maintained for 48 hours at a temperature of 2° to 25°C. When opening a bottle containing sugammadex, it is necessary to strictly observe the rules of asepsis. use of the drug should begin without delay. If sugammadex is used in a delayed manner, the doctor is responsible for observing the time and storage conditions prior to its use. If the dilution was performed under uncontrolled and invalid aseptic conditions, the storage time of the diluted solution should not exceed 24 hours at a temperature of 2° to 8°C. Any remaining contents of the infusion line vials after the use of sugammadex should be disposed of in accordance with the applicable regional requirements.

Influence on the ability to drive motor vehicles and manage mechanisms

After using the drug, you should avoid performing potentially dangerous activities that require a high rate of psychomotor reactions, such as driving a car or operating mechanisms.

Form of production

Solution for intravenous use

Storage conditions

In a dark place, at a temperature of 2-30 °C

Shelf life

3 years

Active ingredient

Sugammadex

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

Children by doctor’s prescription, Adults by doctor’s prescription