Thyssukol Kit - instructions for use, dose, side effects, contraindications

Similar drugsTo uncover

Dosage form: & nbsplyophilizate for the preparation of a solution for topical application [fibrin glue]

Composition:

Tissukol Kit contains two components of fibrin glue and a kit for its preparation and application.
Thibs: freeze-dried, fermented concentrate of binding protein¹.
1 ml of Tissukol solution contains:
-Coagulating proteins - 75-115 mg
-including: Fibrinogen - 70-110 mg
-Fibronectin plasma (CIG) - 2-9 mg
-Factor XIII - 10-50 units.²
- Plasminogen - 40-120 mcg

A solution of aprotinin (bovine) - 300 EEC³/ ml
Thrombin 4 (human), lyophilized with 1 ml of the prepared solution contains - 4 ME⁴
Thrombin 500 (human), lyophilized with 1 ml of the prepared solution contains - 500 IU
Calcium chloride solution 40 μmol CaCl₂/ ml
Kit for restoration of lyophilizates and application of two components of glue with application of the application system Duploject¹The vial contains a magnetic stirrer to facilitate the recovery process in the Fibrinotherm unit

²One unit (unit) corresponds to the amount of factor XIII contained in 1 ml of fresh normal plasma
³3000 units of the activator of cadendnogenase (EIC) = 3.4 EFE (European Pharmacopoeial Units)
⁴One international unit (ME) of thrombin is defined as the activity corresponding to 0.0853 mg of the First International Standard of Human Thrombin

Description:Component 1
Thyssukol is a white lyophilizate with a stirring magnet Aprotinin - clear, colorless solution
Component 2
Human thrombin - white lyophilizate
Calcium chloride is a clear, colorless solution

Pharmacotherapeutic group:Hemostatic agent for topical application; adhesive for topical use.

ATX: & nbsp

Hemostatic preparations for topical application

Pharmacodynamics:During the preparation of the glue, 2 components are mixed using the Tissukol Kit.
To obtain the first component of the adhesive, the lyophilized Tissukol is dissolved in a solution of aprotinin. To obtain a second component of the adhesive, lyophilized thrombin dissolves in a solution of calcium chloride.
The two components are mixed immediately before application. This leads to a thickening of the Tissukol solution - thrombin, which quickly turns into a white, elastic mass, firmly adhering to the tissue.
This preparation process repeats the main stages of the physiological process of blood clotting: fibrinogen by thrombin, factor XIII and calcium ions is converted first into fibrin monomer and then into fibrin polymer.As a result, hemostasis is achieved, gluing and fixing of tissues, as well as acceleration of wound healing. During the healing of the wound, the clot of fibrin glue formed completely dissolves.
To prevent premature lysis, add aprotinin (3000 EIC / ml), a natural protease inhibitor. Dilution of the aprotinin solution leads to an acceleration of the effect of the adhesive and / or allows the fixation of tissues with a lower intrinsic fibrinolytic activity. This applies, for example, to cases where it is necessary to glue nerves for which the effective concentration of the aprotinin solution is only 100 IU / ml.
The rate of film formation depends on the concentration of the thrombin solution used. With a thrombin concentration of 4 IU / ml, this process takes 30-60 seconds, but the formation of the film can be completed in a few seconds with a higher thrombin concentration of 500 IU / ml.

Indications:Stop bleeding, fixation or gluing of tissues and acceleration of wound healing. In some cases, a biocompatible material such as collagen fibers is used as the carrier substance or to enhance the result. The main indications for use are:
Hemostasis
Stopping of diffuse bleeding after surgical operations on bones and joints, adenoidectomy and tonsillectomy, as well as after dental operations in patients with blood clotting disorder, plugging the prostate bed after prostatectomy.
Fixation of tissues
Creation of membranes and attachment of vascular prostheses, tympanoplasty, treatment of fistulas of fluid flow pathways and dural dermis damage, treatment of premature rupture of the fetal bladder during pregnancy by fixing the lower amniotic area, seam isolation on the lung parenchyma and pleura, seams on the trachea, bronchi and esophagus, effusion in malignant lesions, restoration of the lens capsule after traumas with perforation, sealing of joints in order to prevent their insolvency in intestinal a bothersome, additional strengthening of cross-linked microvascular anastomoses, etc.
Bonding fabrics
Bonding of the parenchyma in operations on the kidneys, liver, spleen and pancreas, transplantation of spongy tissue with filling of bone defects and cavities, pleurodesis with spontaneous pneumothorax, fixation of skin grafts and flaps,attachment of bone-cartilage fragments and implants, gluing of peripheral nerves, plastic surgery after opening of the maxillary (maxillary) sinus. Acceleration of wound healing
Skin transplantation on devascularized and infected recipient sites, treatment of skin necrosis and ulcers of the mucous membranes, implantation of homologous bone implants.

Contraindications:Established hypersensitivity to bovine proteins.
Tissukol Kit is not intended as the only means to stop severe arterial or venous bleeding.
As a rule, solutions of Thyssukol and thrombin should not be used as injections.
If, in well-founded cases, the decision of the treating physician prescribes the injection of Tissukol and thrombin solutions into the tissue or blood vessel, the risk of an anaphylactic reaction increases, and with intravascular injection an additional risk of thromboembolism.

Pregnancy and lactation:The safety of fibrin glue during pregnancy or breastfeeding has not been studied in controlled clinical trials. Experiments on animals do not allow us to judge the safety of the drug with respect to the effect onreproductive function, development of the embryo or fetus, the course of pregnancy and peri- and postnatal development.
Thus, the drug should be given to pregnant and lactating women only in case of obvious need.

Dosing and Administration:1. Dosage and drug concentrations
The applied dose of Tissukol solution depends on the size of the surface to be fixed or covered, on the size of the damage to be filled, and on the applied application method.
The amount of glue applied must be determined individually by the attending physician. Usually 2 - 5 ml of a solution of fibrin glue is sufficient. In some cases, for example, with a liver injury or treating large burns, more fibrin glue may be required.
The initial amount of adhesive used should be sufficient to completely cover the application area. If necessary, use the drug again. However, repeated application to the already polymerized area should be avoided, since adhesion will not occur. Usually one can be guided by the fact that one set of "Tissukol Kit" (i.e.1 ml of Tissukol solution plus 1 ml of thrombin solution) will be sufficient for sealing surfaces with an area of at least 10 square meters. cm.
When applying glue by spraying the same amount is enough to cover the surface area of 25 to 100 square meters. see, depending on the individual indications and the specifics of the case.
A high concentration of thrombin is required to stop bleeding, and a low concentration is used to glue the tissues, since the time necessary to fix the edges of the wound is prolonged.
Note. Dry the place intended for glue application, as far as possible.
2. Preparation of components.
Before dissolving the components of the adhesive, disinfect the rubber plugs of all the vials that will be used.
1) Preparation of a Thyssukol Solution (First Component)
A solution of aprotinin with a concentration of 3000 EEC / ml was added to the lyophilized Tissukol. To obtain lower concentrations, this solution is diluted with water for injection.
Note. To fix nerves is used aprotinin with a concentration of about 100 EEC / ml. To obtain this concentration, dilute 0.2 ml of a solution with 5 ml of water for injection.
In the case of filling bone defects with a mixture of fibrin glue and spongy tissue aprotinin usually not used. In this case, the lyophilized Tissukol is dissolved in the required amount of water for injection.
There are two ways of dissolving lyophilized Tissukol:
1. Using the Fibrinotherm.
2. In a water bath at a temperature of 37 ° C.
Preparation of a solution using a Fibrinotherm device The fibrinotherm maintains a constant temperature of 37 ° C. In addition, it reduces the dissolution time of the lyophilized Tissukol due to a magnetic stirrer located in each Tissukol bottle and rotated by a magnet built into the device.
1. Place vials containing lyophilized Thyssukol and aprotinin into the fits of the fibrinotherm that fit in the size and turn on the red switch. When the temperature reaches 37 ° C in Fibrinotherm, the red warning light will light up. Warm the vials for about 3 minutes.
2. Transfer the aprotinin solution to a vial of lyophilized Thyssukol using a blue syringe that is in the package (or a syringe that has already been used to dilute the aprotinin solution).
3.Place the Thyssukol vial in the largest Fibrinotherm socket (use adapters if necessary). Turn the agitator on using the green switch and mix the contents for 8-10 minutes. If insoluble particles are present in the solution, continue mixing until completely dissolved.
Leave the prepared solution in the device at a constant temperature of 37 ° C without mixing, unless you use it immediately.
Preparation of the solution in a water bath
1. Warm vials with lyophilized Thyssukol and aprotinin solution for about 3 minutes in a water bath at a temperature of 33-37 ° C. (Avoid overheating over 37 ° C).
2. Transfer the aprotinin solution to a vial of lyophilized Thyssukol using a blue syringe that is in the package (or a syringe that has already been used to dilute the aprotinin solution).
3. Put the Tissukol vial back into the water bath (37 ° C) for 1 min.
4. Rotate the bottle with your hands to stir the resulting solution, but do not allow excessive pricing. After that, place the vial on a water bath (37 ° C) for another 10 to 15 minutes or until Tissukol is completely dissolved.Leave the prepared solution in a water bath at a constant temperature of 37 ° C without stirring unless you use it immediately.
Note. To avoid contamination, use special precautions when using a water bath: do not immerse the caps of the vials in water.
2) Preparation of thrombin solution (second component)
Depending on the required concentration of thrombin, transfer the required amount of calcium chloride either to a vial of lyophilized thrombin 500 (for rapid clotting) or to a vial of thrombin 4 (for slow clotting). To prepare thrombin solution, use one of the sterile syringes with black markings included in the kit.
Rotate the vial until the lyophilizate is completely dissolved and hold it until use at a temperature of 33 - 37 ° C.
Before use, dial this solution into the second syringe with the black markings included in the kit.
Note. The syringes and needles that were used to dissolve one component should not be reused to dilute the other component, as this will result in the solidification of the corresponding component in the syringe orvial.
3. Methods of application.
Immediately before use, the solutions must be heated to a temperature of 33 - 37 ° C. Do not heat above 37 ° C. Do not use a microwave oven to warm up the components of the preparation.
The components of the adhesive are applied together:
- using the Duploject system and the application needle;
- using the Duploject system, the spray head and the spraying device;
- using the Duploject system and the application catheter.
The Duplojeckt system allows simultaneous application of equal amounts of two components and guarantees their quick and thorough mixing, which is necessary to achieve the optimum strength of the glue. You can use thrombin any concentration.
Co-deposition using the Duploject system and the application needle. The sterile system of the Duploject consists of a cassette for two identical disposable syringes and a common piston that allows the equal amount of two components to enter the application needle through the junction in which they are mixed.

Work instruction:
- place the syringes filled with solutions of Tissukol and thrombin in the cassette Duplozhekt.Both syringes should contain identical volumes of solutions without any air bubbles;
- Insert the spouts of both syringes into the connector and make sure that they are firmly seated. Fasten this assembly by fastening the strap to the cassette;
- Pull the applicator needle on the connector. Do not attempt to remove any remaining air in the connector or applicator needle, since the needle hole may be clogged before applying the glue;
- Apply glue to the surface of the wound or on the surface of the tissues that need to be bonded.
In cases where a small amount of glue (1-2 drops) is needed, squeeze and remove a few first drops of glue from the application needle just before use so that the two components are evenly mixed.
Note. To ensure the correct tight fit of the connector, use only the syringes that come with the Duplozhekt system.
If the process of applying two components using the Duploject system and the application needle is interrupted, replace the needle with a new one (3 spare needles included) before resuming the application.
Only replacing the application needle immediately before resuming the application process will help avoid the formation of a plug in the lumen of the connector assembly (in this case use the spare connector that is included). Co-deposition using the Duploject system, spray head and spraying device is used to treat wounds with a large surface, for example, in case of tissue transplantation (skin) or to stop diffuse bleeding. Two syringes containing solutions of Thyssukol and thrombin are placed in a double cassette of the Duploject system and connected to a spray head in which solutions are supplied to two separate outlets. From the third hole located above these two outlets, a jet of gas is ejected in such a way that the components of the glue are well mixed. The pressure and flow rate of the gas are monitored by means of a sprayer. A detailed description of the method is included in the instructions for the sprayer.
Application using the Duploject system and the application catheter is used in operating areas, access to which is difficult,and in minimally invasive surgery. A detailed description of this method is included in the instructions for the application catheter.
After applying the preparation, leave the surface for at least 2 minutes in order for the glue to polymerize.
Note. In operations requiring the filling of bone defects or the alignment of the wound area, the glue components can be pre-mixed with a spongy tissue or other material. In this case, a thrombin solution with a concentration of 4 IU / ml should be used.
To prevent adhesion of glue to gloves and tools, moisten them with saline (physiological) solution before contact with glue.

Side effects:In patients receiving fibrin glue / hemostatics, in rare cases, hypersensitivity reactions such as bradycardia, tachycardia, arterial hypotension, hot flashes, bronchospasm, wheezing, dyspnea, nausea, urticaria, angioedema, itching, erythema, paresthesia.
In some cases, these reactions can lead to severe anaphylactic shock, especially when the drug is applied repeatedly, or used by patients with hypersensitivity to aprotinin or any other components of the drug.
Even in the case where the second course of treatment with fibrin glue was well tolerated, subsequent application of fibrin glue or systemic application of aprotinin can cause severe anaphylactic reactions.
If hypersensitivity symptoms occur, the drug should be discontinued immediately and take the necessary measures to provide emergency care. Accidental administration of the drug in soft tissue can lead to anaphylactoid reaction and / or local tissue damage.
Antibodies to the components of fibrin glue occur rarely.
With intravascular injection, there is a risk of developing thromboembolism and an anaphylactic reaction.
For safety regarding infectious agents, see "Special instructions".
Undesirable reactions recorded during clinical trials are listed below. The frequency is estimated as follows: often (from ≥ 1/100 to <1/10); infrequently (from ≥ 1/1000 to <1/100); rarely (from ≥ 1/10000 to <1/1000).
From the cardiovascular system: rarely - hypotension.
From the gastrointestinal tract: infrequently - nausea
From the side of laboratory indicators: infrequently - increase in blood concentrations of fibrin degradation products
Other: infrequent - pain during the procedure.
Undesirable reactions recorded during post-marketing surveillance are given below, without indicating the frequency of occurrence.
On the part of the immune status of hypersensitivity reactions, including anaphylactic reactions, anaphylactic shock, as well as the following manifestations: angioedema, paresthesia, bradycardia, tachycardia, hot flashes, bronchospasm, dyspnea, wheezing, urticaria, pruritus, erythema. With anaphylactic shock, there were fatal outcomes.
From the side of the cardiovascular system: arterial embolism, including embolism of the vessels of the brain, brain infact. (The cerebral infarction was the result of intravascular injection in the region of the upper stony sine).
From the skin and subcutaneous tissue: slowing of wound healing.
Adverse events inherent in this pharmacological class of drugs: air or gas embolism as a consequence of the use of a spray device; hypersensitivity - irritation in the place of application, chest tightness, chills, headache, drowsiness, anxiety, vomiting.

Overdose:There are no reports of symptoms of an overdose of Tissukol Kit.

Interaction:Cases are unknown.
In comparison with other similar products or solutions of thrombin, the protein can be denatured by the action of solutions containing alcohol, iodine or heavy metals (for example, solutions of antiseptics). Such substances should be removed to achieve the best effect before using the drug.
Do not apply Tissukol Kit together with preparations containing oxidized cellulose, as this can lead to a decrease in Tissukol's effectiveness.

Special instructions:As a rule, solutions of Thyssukol and thrombin should not be used as injections. If, in well-founded cases, the injection of Tissucol and thrombin solutions into a tissue or blood vessel is prescribed by the doctor's decision, there is a risk of an anaphylactic reaction, and with intravascular injection, an additional risk of thromboemolism. Avoid injection of the drug in an area with a large number of blood vessels, for example, in the nasal cavity.
Since solutions of Thyssukol and thrombin can be denatured by contact with solutions containing alcohol, iodine or heavy metals (for example, antiseptic solutions), such substances should be removed before applying the adhesive.
When using Tissukol and thrombin solutions, if possible, cover areas adjacent to the bonding site.
It is necessary to avoid the sequential application of two components of fibrin glue. Tissukol Kit must be applied only in a thin layer. Applying a layer of greater thickness can reduce the effectiveness of the drug and hinder the process of wound healing.
When using the sprayer, the pressure range recommended by the manufacturer must be carefully monitored. In the absence of special recommendations, the pressure should not exceed 1.4 - 1.7 bar. Do not spray closer than at a distance recommended by the manufacturer. In the absence of special instructions do not spray closer than 10 -15 cm from the wound surface. Any use of compressed gas can be a potential risk that causes emphysema, tissue rupture, or gas embolism, which can be life threatening. It must be ensured that all the necessary precautions have been taken to eliminate this risk. When applying Tissukol by spraying it is necessary to control blood pressure, pulse, saturation with oxygen and carbon dioxide because of the possibility of air or gas embolism.
When spraying Thyssukol in a confined space, the risk of a compression complication should be taken into account.
As with any product containing protein, hypersensitivity reactions are possible. Symptoms of allergic reactions may include bradycardia, tachycardia, lowering blood pressure, hot flashes, bronchospasm, dyspnoea, nausea, generalized urticaria, rash, itching, dermatitis, paresthesia, anaphylactic shock. If these phenomena occur, the drug should be discontinued immediately.
Fibrin glue contains bovine protein (aprotinin), the use of which can cause anaphylactic reactions. Even in the case of strictly local application, there is a risk of developing anaphylactic reactions associated with the presence of aprotinin. The risk increases in cases of prior contact, even with good tolerability. Thus, any use of aprotinin or aprotic n-containing drugs should be noted in the patient's medical history. Standard measures to prevent infections resulting from the use of drugs derived from human blood or plasma include selection of donors,Screening of individual donor samples and blood plasma pools in order to identify specific markers of infection, as well as use in the production of effective inactivation / removal of viruses. Despite this, when using drugs derived from human blood and plasma, transmission of an infectious agent can not be completely ruled out. This also applies to unknown or new viruses and other pathogenic pathogens. The measures taken are considered effective against envelope viruses, such as HIV-1/2, HBV, HCV, and the non-enveloped HAV virus.
The technologies used for removal and inactivation may not be effective enough for some non-enveloped viruses, such as, for example, parvovirus B19. Infection with parvovirus B19 can be dangerous for pregnant women (infection of the fetus) and patients with immunodeficiency, for patients with increased erythrocyte decay (eg, hemolytic anemia).
Each time a Tissukol Kit is administered to a patient, it is necessary to record the name of the drug and the serial number in the patient's medical history.

Effect on the ability to drive transp. cf. and fur:Not noted.

Form release / dosage:Liofilizate for the preparation of a solution for topical application [fibrin glue]

Packaging:A set of transparent bottles with a filling of 0.5, or 1, or 2, or 5 ml of glass - type I Heb. F. (a bottle of Tissukol with a filling of 5 ml of glass - type P Hebrew F.), corked with rubber stoppers and aluminum caps under running in, covered with plastic caps like "Flip-off". The set consists of: 1 box - lyophilized powders: Tissukol (1 vial with magnetic stirrer), Thrombin (2 vials - 4 and 500 ME); solutions: Aprotinin (1 bottle), Calcium chloride (1 bottle); All components in a cardboard insert with vial cells are placed in a cardboard box.
2 carton: application set "Duplozhekt". A double cassette for syringes with a common piston, a connecting unit (2 pgs.), Disposable syringes (4 pcs.) And disposable needles (application needles 4 pcs, needles for the preparation of solutions 4 pcs.) Are placed in combined bags (paper / polyethylene) and in a cardboard box. Both boxes are placed in a common sleeve-type package. The kit includes the Instruction for use.

Storage conditions:Store in a dark place at a temperature of 2 ° to 8 ° C. Do not freeze.Keep out of the reach of children.

Shelf life:30 months.
The actual shelf-life of the drug may be less than 30 months, in which case it is determined by the shelf life of the component having the least remaining shelf life at the time the kit is formed.
Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N 014732/01

Date of registration:05.03.2009

Date of cancellation:2016-04-05

The owner of the registration certificate:Baxter AGBaxter AG Austria

Manufacturer: & nbsp

BAXTER, AG Austria

Information update date: & nbsp2016-02-20

Illustrated instructions

Instructions

Thysukol Kit (Tissucol Kit)