Tisseel lyo

Package leaflet: Information for the user

TISSEEL Lyo – powders and solvents for preparing a tissue adhesive
Human fibrinogen, human thrombin, synthetic aprotinin, calcium chloride dihydrate
Please read all of this leaflet carefully before this medicine is administered because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you get any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

1. What TISSEEL Lyo is and what it is used for
2. Important information before use of TISSEEL Lyo
3. How to use TISSEEL Lyo
4. Possible side effects
5. How to store TISSEEL Lyo
6. Contents of the pack and other information

1. What TISSEEL Lyo is and what it is used for

What TISSEEL Lyo is
TISSEEL Lyo is a two-component tissue adhesive composed of two solutions: a solution of adhesive proteins and a thrombin solution. TISSEEL Lyo contains fibrinogen and thrombin. These are two blood proteins essential for blood coagulation. When these proteins mix during application, they form a clot at the site where the surgeon applies them.
The clot formed by TISSEEL Lyo is very similar to a natural blood clot. It dissolves in the same way as an endogenous (naturally occurring) clot and leaves no residue. The addition of a synthetic protein (synthetic aprotinin) aims to increase the durability of the clot and prevent its premature dissolution.

For what TISSEEL Lyo is used
TISSEEL Lyo is used as an adjunctive treatment when standard surgical techniques are not sufficiently effective:

• to improve haemostasis;
• as a tissue adhesive to facilitate wound healing or as a suture sealant in vascular and gastrointestinal surgery;
• for bonding tissues, e.g. securing skin grafts.
  TISSEEL Lyo is also effective in patients receiving heparin-containing medications that inhibit blood coagulation.

2. Important information before using TISSEEL Lyo

When not to use TISSEEL Lyo:

• in case of allergy (hypersensitivity) to any of the active substances or to any of the other components of this medicine.
• for the treatment of massive arterial or venous bleeding. The use of TISSEEL Lyo alone is not indicated in such situations.
• TISSEEL Lyo must not be injected into blood vessels (veins or arteries). Since TISSEEL Lyo forms clots at the site where it is applied, injecting TISSEEL Lyo may cause clot formation within a blood vessel. If such a clot travels through the bloodstream, it may lead to life-threatening complications.
• TISSEEL Lyo is not indicated as a substitute for skin sutures used to close a surgical wound.

Warnings and precautions
Before starting treatment with TISSEEL Lyo, discuss it with your doctor, pharmacist, or nurse.
Extreme caution should be exercised when using TISSEEL Lyo due to the possibility of allergic hypersensitivity reactions.
Early signs of an allergic reaction may include:

• transient skin redness
• itching
• rash
• nausea, vomiting
• general malaise
• chills
• chest tightness
• swelling of lips and tongue
• difficulty breathing / apnea
• drop in blood pressure
• increased or decreased heart rate

If any of these symptoms occur, application must be stopped immediately. In case of severe symptoms, emergency treatment must be initiated immediately.

• because TISSEEL Lyo contains a synthetic protein called aprotinin. Even though this protein is administered only in small amounts and only onto the wound surface, there is a risk of severe anaphylactic reaction. This risk appears to be higher in patients previously treated with TISSEEL Lyo or aprotinin, even if it was previously well tolerated. Therefore, information regarding prior use of aprotinin or products containing aprotinin should be documented in the patient's medical history. Since synthetic aprotinin is structurally identical to bovine aprotinin, the use of TISSEEL Lyo in patients with allergy to bovine proteins should be carefully considered.
• because inadvertent administration into a blood vessel may lead to life-threatening complications due to embolization of the formed clot into the bloodstream.
• intravascular administration, particularly in sensitive patients, may increase the likelihood and severity of acute hypersensitivity reactions. Especially during cardiothoracic procedures, the physician must exercise particular caution to avoid injecting TISSEEL Lyo into a blood vessel. It is equally important to avoid injection into the nasal mucosa due to the risk of clot formation in the arteries around the eyes.
• because there is a risk of local tissue damage if TISSEEL Lyo is injected into tissue.
• to prevent unwanted adhesion of tissues. Therefore, before application, ensure that surrounding areas outside the intended site of application are adequately protected.
• because excessive thickness of the formed clot may adversely affect the product's efficacy and wound healing process. Therefore, TISSEEL Lyo should be applied only in a thin layer.

Caution should be exercised when applying fibrin glue using compressed gas.
Very rare cases of life-threatening or fatal air and gas embolism (air entering the bloodstream, which may lead to serious health risks or death) have been reported during the use of spray devices equipped with pressure regulators for applying fibrin tissue adhesives to tissues. This appears to be associated with using the spray device at pressures higher than recommended and/or held very close to the tissue surface. The risk appears to be greater when tissue fibrin adhesives are sprayed with air compared to spraying with CO₂. Therefore, such an event cannot be excluded when spraying TISSEEL Lyo onto surgically treated open wounds.
Instructions for use, including the manufacturer's recommendations regarding pressure ranges and distance from the tissue surface during spraying, are provided with the spray device and its additional nozzle.
TISSEEL Lyo must be administered strictly according to instructions and only with devices recommended for use with this product.
During spraying of TISSEEL Lyo, blood pressure, pulse, arterial oxygen saturation, and end-tidal CO₂ concentration should be monitored due to the risk of gas embolism.

For medicines manufactured from human blood or plasma, specific measures are taken to prevent transmission of infections to patients. These include:

• careful selection of blood and plasma donors to ensure exclusion of high-risk groups for infection carriers
• testing of individual blood donations and pooled plasma for viruses or infections
• inclusion of processing steps in the manufacturing process of blood or plasma that can inactivate or remove viruses.

Despite these measures, when administering medicines derived from human blood or plasma, the possibility of transmitting infection cannot be completely excluded. This also applies to unknown and newly discovered viruses as well as other pathogens.
These measures are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and non-enveloped hepatitis A virus. These measures may have limited effectiveness against certain non-enveloped viruses, such as parvovirus B19.
Parvovirus B19 infection may be dangerous for pregnant women (fetal infection) and for individuals with weakened immune systems or certain types of anemia (e.g., congenital spherocytosis or hemolytic anemia).
The treating physician may recommend that the patient consider vaccination against hepatitis A and B viruses if the patient is receiving fibrin glue repeatedly.
It is strongly recommended that the name and batch number of TISSEEL Lyo be documented each time it is administered, using the self-adhesive label provided, which should be affixed to the patient's medical record.

TISSEEL Lyo and other medicines
Inform your doctor or pharmacist about all medicines currently taken or recently taken, including those available without a prescription.
No interactions with other medicinal products are known.
Like other similar preparations or thrombin solutions, this product may be denatured by solutions containing alcohol, iodine, or heavy metals (e.g., antiseptic solutions).
Before application, the surface should be thoroughly cleaned of such substances.
Information regarding preparations containing oxidized cellulose is provided in the section Preparation for use.

TISSEEL Lyo with food and drink
Ask your doctor. The doctor will decide whether the patient may eat or drink before administration of TISSEEL Lyo.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine. The doctor will decide whether TISSEEL Lyo can be used during pregnancy or breastfeeding.

Driving and operating machinery
TISSEEL Lyo has no effect on the ability to drive motor vehicles or operate machinery.

TISSEEL Lyo contains Polysorbate 80
Polysorbate 80 may cause local skin reactions such as contact dermatitis.

3. How to use TISSEEL Lyo

TISSEEL Lyo must be used only by experienced surgeons who have received appropriate training.
Before applying TISSEEL Lyo, the wound surface should be dried using standard techniques (e.g. gauze pads, swabs, suction devices).
Compressed air or gas must not be used to dry the surface.
TISSEEL Lyo may only be sprayed onto visible surfaces.
When applying TISSEEL Lyo using a spray device,
the manufacturer's recommendations regarding pressure and distance from the tissue must be followed,
within the ranges specified below:

During spraying of the TISSEEL Lyo product, arterial blood pressure, heart rate, arterial oxygen saturation, and end-tidal CO₂ concentration should be monitored due to the risk of air or gas embolism (see section 2).
The amount of glue applied is always determined based on individual needs.
The dose depends on several factors, including the type of surgical procedure, the size of the area to be glued, the chosen method of glue application, and the number of applications. The physician will decide how much is needed and will apply an appropriately thin, even layer onto the target surface. If the amount applied does not appear sufficient, application of the glue may be repeated.
When applying TISSEEL Lyo, clot formation occurs rapidly. Applying a new layer onto an already existing layer of TISSEEL Lyo should be avoided, as the new layer will not adhere properly to the existing one.
It is absolutely essential to avoid separately applying the fibrinogen-containing component and the thrombin-containing component. In clinical studies, individually adjusted doses ranged from 4 to 20 ml. In certain procedures (e.g., traumatic liver injury or management of extensive burn wounds), larger volumes may be required.
As a general guideline for surface gluing, one 2 ml TISSEEL Lyo kit (i.e., 1 ml Tisseel solution plus 1 ml thrombin solution) is sufficient to cover an area of at least 10 cm².
When TISSEEL Lyo is applied by spraying, the same volume will be sufficient to cover proportionally larger surface areas.
To avoid excessive granulation and to ensure gradual absorption of the formed clot into tissues, TISSEEL Lyo should be applied in as thin layers as possible (see section 2).
To ensure proper mixing of the fibrinogen solution and thrombin solution, the first few drops of the product should be expelled from the application needle directly before use and discarded immediately prior to applying the preparation.
Use of higher than recommended doses of TISSEEL Lyo
TISSEEL Lyo is used exclusively during surgical procedures. The physician determines the amount required for application. No cases of overdose have been reported.
If there are any questions regarding the use of the medicinal product, please consult a physician or pharmacist.
Use in children
The safety and efficacy of TISSEEL Lyo in children have not been established.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the adverse reactions worsen or if any adverse reactions not listed in this leaflet occur,
a doctor or pharmacist should be informed immediately.
In patients treated with tissue glue, hypersensitivity reactions or allergic reactions may occur.
Although these are very rare, they may be serious.
Early signs of an allergic reaction may include:

• transient skin redness
• itching
• rash
• nausea, vomiting
• headache
• drowsiness
• restlessness
• burning and stinging at the site of administration
• tinnitus
• chills
• chest tightness
• swelling of lips, tongue, and throat (which may cause difficulty in breathing and/or swallowing)
• difficulty breathing
• low blood pressure
• increased or decreased heart rate
• loss of consciousness due to low blood pressure

In isolated cases, these reactions may progress to severe allergic reactions (anaphylaxis).
Such reactions may occur especially when the product is used repeatedly or administered to patients
who previously experienced hypersensitivity to aprotinin or to any other component of the product.
Even if previous multiple administrations of TISSEEL Lyo were well tolerated, subsequent administration
of TISSEEL Lyo or injection of aprotinin may lead to severe allergic (anaphylactic) reactions.
The surgical team performing the procedure is aware of the risk of such reactions and will immediately
discontinue administration of TISSEEL Lyo if early signs of hypersensitivity occur.
Severe symptoms may require emergency interventions.
Injection of TISSEEL Lyo into soft tissues may cause local tissue damage.
Injection of TISSEEL Lyo into blood vessels (veins or arteries) may lead to clot formation (thrombosis).
Since TISSEEL Lyo is manufactured from plasma derived from human donor blood, the risk of infection
cannot be completely excluded. Nevertheless, the manufacturer takes numerous measures to reduce this risk (see section 2).
In rare cases, antibodies against components of the tissue glue may develop.
The following adverse reactions have been observed during treatment with TISSEEL Lyo:
Adverse reactions were classified according to the following frequency categories:
Very common: may affect more than 1 in 10 people
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people
Rare: may affect up to 1 in 1,000 people
Very rare: may affect up to 1 in 10,000 people
Not known: frequency cannot be estimated from the available data

* The occurrence of air or gas bubbles in the vascular system has been reported when fibrin
glues are applied using devices with compressed air or gas; this appears to be associated with
improper use of the spray device (e.g. at higher than recommended pressure and/or at a closer
distance to the tissue surface than recommended).
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in the package leaflet,
inform your doctor or nurse.
Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug
Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: + 48 22 49 21 301
Fax: + 48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to enhance the safety information on the medicinal product.

5. How to store TISSEEL Lyo

Keep the medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label.
Store below 25°C. Do not freeze.
Keep the vials in the outer cardboard packaging to protect from light.
If the reconstituted solutions are not used immediately, they may be stored at 37°C
or at room temperature (not exceeding 25°C) without mixing for no longer than 4 hours.
TISSEEL Lyo product must not be exposed to temperatures above 37°C and must not be
subjected to microwave radiation. Reconstituted solutions must not be placed under refrigerated conditions or frozen.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What TISSEEL Lyo contains
TISSEEL Lyo consists of two components:
Component 1: Fibrin proteins solution
To obtain the fibrin proteins solution, the fibrin proteins concentrate (lyophilized) must be dissolved in the aprotinin solution.

1. The active substance in the fibrin proteins concentrate is: human fibrinogen, 91 mg/ml.
   Other components are: human albumin, L-histidine, nicotinamide, polysorbate 80 (Tween 80), sodium citrate dihydrate.
   1a) The active substance in the aprotinin solution (solvent for the fibrin proteins concentrate) is: synthetic aprotinin, 3000 KIU/ml.
   Other component: water for injections.
   Component 2: Thrombin solution
   To obtain the thrombin solution, thrombin (lyophilized) must be dissolved in calcium chloride solution.
2. The active substance in thrombin (lyophilized) is: human thrombin, 500 IU/ml.
   Other components are: human albumin and sodium chloride.
   2a) The active substance in the calcium chloride solution (solvent for thrombin powder) is: calcium chloride dihydrate, 40 μmol/ml.
   Other component: water for injections.

TISSEEL Lyo contains human Factor XIII, co-purified with human fibrinogen, in amounts of
0.6 – 5 IU/ml.
What TISSEEL Lyo looks like and contents of the pack
All components of TISSEEL Lyo are contained in glass vials. The vial containing Tisseel adhesive protein powder is equipped with a magnetic stirrer.
The lyophilized components are white or slightly yellowish and have the consistency of powder or granules; the liquid components are clear, colourless or slightly yellowish.
Contents of the pack:
1 vial containing Tisseel protein powder (adhesive proteins) (component 1, lyophilized, containing 91 mg/ml human fibrinogen)
1 vial containing thrombin powder (component 2, lyophilized, containing 500 IU/ml human thrombin)
1 vial containing synthetic aprotinin solution (solvent for component 1, containing 3000 KIU/ml aprotinin)
1 vial containing calcium chloride solution (solvent for component 2, containing 40 μmol/ml calcium chloride dihydrate)
1 Duploject set for reconstitution and application consisting of:
1 double syringe holder DUPLOJECT
2 connectors
2 single-use syringes with blue scale for Tisseel
2 single-use syringes with black scale for thrombin
4 single-use needles
4 application needles (with blunt end)
Pack size:
TISSEEL Lyo is available in the following pack sizes: 1 x 2 ml (1 ml + 1 ml), 1 x 4 ml (2 ml + 2 ml), and 1 x 10 ml (5 ml + 5 ml).
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Baxter Polska Sp. z o.o.
ul. Kruczkowskiego 8
00-380 Warsaw
Manufacturer:
Takeda Manufacturing Austria AG, Industriestrasse 67, 1221 Vienna, Austria
This medicinal product is authorised for marketing in the European Economic Area countries under the following names:
Austria: TISSEEL Lyo, Pulver und Lösungsmittel für einen Gewebekleber
Bulgaria: ТИСИЛ ЛИО, прахове и разтворители за тъканно лепило
Czech Republic: TISSEEL Lyo, Prášek pro přípravu tkáňového lepidla a rozpouštědlo
Hungary: TISSEEL Lyo, Por és oldószer szövetragasztóhoz
Norway: TISSEEL
Poland: TISSEEL Lyo

Information intended exclusively for medical professionals:

General Information
Before applying TISSEEL Lyo, protect areas of the body not intended for treatment to prevent unwanted adhesion of tissues.
To avoid TISSEEL Lyo adhering to gloves and instruments, moisten them with physiological saline solution prior to contact with the adhesive.
As a general guideline for surface bonding, one 2 ml TISSEEL Lyo kit (i.e., 1 ml fibrinogen protein solution plus 1 ml thrombin solution) is sufficient to cover an area of at least 10 cm².
The required dose depends on the size of the surface to be bonded.
DO NOT use the two components of TISSEEL Lyo separately. Both components must be used together.

Preparation and Reconstitution
Note: Additional information regarding preparation and application is provided in the DUPLOJECT system user manual.
The procedures described below serve as general guidance.
Do not expose to temperatures above 37°C.
Do not expose to microwave radiation.
After reconstitution, the product must be used within 4 hours. Do not store in a refrigerator or freeze.
Aseptic technique must be used during preparation and reconstitution of the fibrin adhesive components.
Before reconstituting the fibrin adhesive components, clean the rubber stoppers of all vials with an appropriate disinfectant, taking care to avoid direct contact with the product.

To obtain the fibrinogen protein solution, dissolve the fibrinogen concentrate in the aprotinin solution.
The thrombin powder is dissolved in calcium chloride solution to form the thrombin solution.
Always use separate syringes and needles for reconstituting the two solutions to prevent premature coagulation.
Both solutions should be clear or slightly opalescent. Visually inspect reconstituted solutions before administration. Do not use solutions that are cloudy, discolored, contain precipitates, or show other visible changes.
Air bubbles may cause the reconstituted fibrinogen protein solution to appear cloudy, but such cloudiness does not impair the efficacy or usability of the product.

I. Reconstitution using the FIBRINOTHERM device
The FIBRINOTHERM device maintains a constant temperature of 37°C and enables dissolution of the lyophilized fibrinogen concentrate through mixing.

Ia. Pre-heating TISSEEL Lyo
Place all four TISSEEL Lyo vials into the pre-heated openings of the FIBRINOTHERM device using appropriately sized adapter rings, and heat the vials for approximately 3 minutes.

Ib. Preparation of the fibrinogen protein solution (Component 1) (FIBRINOTHERM)

• Remove the stoppers from the vials containing the fibrinogen concentrate and the aprotinin solution. Both vials are marked with a blue color.
• Transfer the aprotinin solution into the vial containing the fibrinogen concentrate using one of the needles and a syringe with a blue scale provided in the sterile reconstitution kit (Package A).
• Gently swirl the vial to ensure the fibrinogen concentrate is completely wetted.
• Place the vial into the largest opening of the FIBRINOTHERM device (use adapter rings if necessary).
• Activate the magnetic stirrer and mix until the fibrinogen concentrate is completely dissolved.
• Reconstitution is complete when no undissolved particles are visible.
• If particles remain, facilitate dissolution by gently shaking the vial horizontally (avoid vertical shaking). After visual inspection and/or brief manual mixing, return the vial to the FIBRINOTHERM and continue mixing at 37°C until complete dissolution of the fibrinogen concentrate.
• After dissolution is complete, turn off the magnetic stirrer.

Note:

• If the fibrinogen concentrate does not dissolve completely within 20 minutes, discard the vial and prepare a new kit.
• If the fibrinogen protein solution is not used immediately, store it at 37°C or room temperature without stirring. To ensure homogeneity, gently mix the solution before drawing it up using one of the needles with a blue-scale syringe provided in the sterile application kit (Package B). For TISSEEL Lyo 10 ml, attach a larger needle to the blue-scale syringe.

Ic. Preparation of the thrombin solution (Component 2) (FIBRINOTHERM)

• Remove the stoppers from the vials containing thrombin powder and calcium chloride solution. Both vials are marked with a black color.
• Transfer the calcium chloride solution into the thrombin vial using the second needle and syringe with a black scale provided in the sterile reconstitution kit (Package A).
• Gently swirl to dissolve the lyophilized powder and place the vial into the appropriately sized opening of the FIBRINOTHERM device.
• Store the thrombin solution at 37°C or room temperature if not used immediately. To ensure homogeneity, gently mix the thrombin solution before drawing it up using the second needle with a black-scale syringe provided in the sterile application kit (Package B).

Additional instructions are provided in the FIBRINOTHERM device user manual.

II. Reconstitution using a water bath
Note: When using a water bath for reconstitution, take special precautions to avoid contamination by ensuring the vial, especially the neck, is not fully submerged.

IIa. Preparation of the fibrinogen protein solution (Component 1) (water bath)

• Pre-warm the blue-marked vials containing the lyophilized fibrinogen concentrate and the aprotinin solution for approximately 3 minutes in a water bath maintained at 33°C–37°C.
• Using one of the needles and a syringe with a blue scale from the sterile reconstitution kit (Package A), transfer the aprotinin solution into the vial containing the fibrinogen concentrate.
• Return the vial to the water bath at 33°C–37°C for one minute.
• Gently swirl, avoiding excessive foaming. Return the vial to the water bath and periodically check for complete dissolution.
• Reconstitution is complete when no undissolved particles are visible. If particles remain, continue heating at 33°C–37°C for several additional minutes with gentle shaking until complete dissolution.
• After complete dissolution, if the fibrinogen protein solution is not used immediately, store it at 33–37°C or room temperature. To ensure homogeneity, gently mix the solution before drawing it up using one of the needles with a blue-scale syringe from the sterile application kit (Package B). For TISSEEL Lyo 10 ml, attach a larger needle to the blue-scale syringe.

IIb. Preparation of the thrombin solution (Component 2) (water bath)

• Transfer the contents of the calcium chloride solution vial into the thrombin vial (both marked black) using the second needle and syringe with a black scale from the sterile reconstitution kit (Package A).
• Gently swirl to dissolve the lyophilized powder.
• Place the vial in a water bath maintained at 33°C–37°C.
• Reconstitution is complete when all thrombin powder is dissolved.
• Store the thrombin solution at 33°C–37°C or room temperature until use.
• Before use, draw up the thrombin solution from the vial using the second needle and syringe with a black scale from the sterile application kit (Package B).

III. Application of reconstituted tissue adhesive components
Before administration, warm TISSEEL Lyo to 33°C–37°C.

User Manual

• Both syringes should be filled with equal volumes.
• Remove all air from the syringe before attaching any application device.
• Place the two syringes—one containing the fibrinogen protein solution and the other the thrombin solution—into the dual-syringe holder DUPLOJECT.
• Attach the connector and secure it to the side of the syringe with the safety strap.
• Connect the outlets of both syringes to the connector, ensuring they are properly secured.
  • Secure the connector by fastening the safety strap to the dual-syringe holder DUPLOJECT.
  • If the safety strap breaks, use the spare connector provided in the kit.
  • If no spare connector is available, the kit may still be used, but ensure the connection is secure and leak-proof.
• Attach the application needle to the connector.
• DO NOT remove air remaining in the connector and application needle before starting the actual application, as this may cause clogging of the application needle.

The common plunger of the DUPLOJECT dual-syringe holder ensures simultaneous delivery of equal volumes of both adhesive components through the connector to the application needle, where they are mixed and then applied.

Administration
Before applying TISSEEL Lyo, dry the wound surface using standard techniques (e.g., gauze pads, suction devices).
Do not use compressed air or gas for drying the surface.

• Apply the mixed fibrinogen protein–thrombin solution to the target surface or surfaces to be bonded by slowly depressing the rear part of the common plunger.
• In surgical procedures requiring minimal volumes of fibrin adhesive, it is recommended to expel and discard the first few drops of product.
• After applying TISSEEL Lyo, wait at least 2 minutes to achieve sufficient polymerization.

Note: After mixing the fibrin adhesive components, coagulation occurs within seconds due to the high thrombin concentration (500 IU/mL). Therefore, if application of the fibrin adhesive components is interrupted, the needle may become immediately blocked. In such cases, replace the application needle with a new one immediately before resuming application. If the connector outlets are obstructed, use the spare connector provided in the package.

The fibrin adhesive may also be applied using other additional devices manufactured by BAXTER, specifically designed for use in endoscopy, minimally invasive surgical procedures, or for application on large or hard-to-reach surfaces. When using such devices, strictly follow the manufacturer's instructions for use.

For certain applications, biocompatible materials such as collagen sheets may be used as a carrier or for mechanical reinforcement of tissue apposition.

Application using a spray device
When applying TISSEEL Lyo with a spray device,
follow the manufacturer's recommendations regarding pressure and distance from tissue according to the ranges specified below:

During the spraying of the TISSEEL Lyo product, monitor arterial pressure, heart rate, arterial oxygen saturation, and end-tidal CO₂ concentration due to the risk of air or gas embolism (see section 2).
When administering TISSEEL Lyo into a closed space such as the thoracic or abdominal cavity, use of the DuploSpray MIS applicator and a pressure-regulating system is recommended. Further information is available in the DuploSpray MIS device user manual.
Disposal of residues
Any unused medicinal product or waste material must be disposed of in accordance with local regulations.