Tisseel

The frozen solutions are colorless to pale yellow, opalescent.
After thawing, they are colorless to pale yellow.
Component 1: Sealer protein solution: Human fibrinogen (as clottable protein) 91 mg¹/mL, Aprotinin (synthetic) 3000 KIU²/mL.
Excipient(s) with known effect: Polysorbate 80 0.6-1.9 mg/mL.
Component 2: Thrombin solution: Human thrombin 500 IU³/mL, Calcium chloride dihydrate 40 μmol/mL.
1, 2 or 5 mL sealer protein solution (with synthetic aprotinin) and 1, 2 or 5 mL thrombin solution (with calcium chloride dihydrate) combine to make 2, 4 or 10 mL ready-to-use fibrin sealant solution. (See Table 1.)

Click on icon to see table/diagram/image

TISSEEL Fibrin Sealant with Synthetic Aprotinin contains Human Factor XIII co-purified with Human Fibrinogen in a range of 0.6-5 IU/mL.
¹ Contained in a total protein concentration of 96-125 mg/mL.
² 1 EPU (European Pharmacopoeia Unit) corresponds to 1800 KIU (Kallidinogenase Inactivator Unit).
³ Thrombin activity was determined using the current WHO Standard for thrombin.
Excipients/Inactive Ingredients: Component 1: Sealer protein solution: Human albumin, L-histidine, Niacinamide, Sodium citrate dihydrate, Polysorbate 80 (Tween 80), Water for Injections.
Component 2: Thrombin solution: Human albumin, Sodium chloride, Water for Injections.

Pharmacotherapeutic group: Local hemostatics. ATC code: B02BC. Tissue adhesives. ATC code: V03AK.
Pharmacology: Pharmacodynamics: The fibrin adhesion system imitates the last phase of physiological blood coagulation.
Conversion of fibrinogen into fibrin occurs by the splitting of fibrinogen into fibrin monomers and fibrinopeptides. The fibrin monomers aggregate and form a fibrin clot. Factor XIIIa, which is generated from Factor XIII by the concerted action of thrombin and calcium ions, stabilizes the clot by the cross-linking of fibrin fibres.
As wound healing progresses, increased fibrinolytic activity is induced by plasmin, and decomposition of fibrin to fibrin degradation products is initiated. Proteolytic degradation of fibrin is inhibited by anti-fibrinolytics. Aprotinin is present in TISSEEL Fibrin Sealant with Synthetic Aprotinin as an antifibrinolytic to prevent premature degradation of the clot.
To prove the efficacy, in vivo studies with four animal models which imitated the patient situation as closely as possible, were carried out. TISSEEL Fibrin Sealant with Synthetic Aprotinin was effective with regard to primary and secondary hemostasis as well as wound healing.
Clinical studies demonstrating hemostasis and suture support were conducted in a total of 213 patients (120 with TISSEEL Fibrin Sealant with Synthetic Aprotinin, 93 with control) undergoing vascular surgery with ePTFE conduits, in a total of 70 patients (35 with TISSEEL Fibrin Sealant with Synthetic Aprotinin, 35 with control) undergoing partial hepatic resection and in a total of 317 patients (157 with TISSEEL Fibrin Sealant with Synthetic Aprotinin, 160 with a predecessor single virus inactivated form of the product as control) undergoing cardiac surgery with a cardiopulmonary bypass and median sternotomy.
Efficacy of TISSEEL Fibrin Sealant with Synthetic Aprotinin as an adjunct to conventional surgical methods in sealing colonic anastomoses in trauma patients undergoing closure of temporary colostomies has been demonstrated in a randomized, controlled, prospective, single-center study conducted in 1986 in a total of 120 patients (61 with TISSEEL Fibrin Sealant with Synthetic Aprotinin, 59 with control).
Pharmacokinetics: TISSEEL Fibrin Sealant with Synthetic Aprotinin is intended for epilesional use only. Intravascular administration is contraindicated. As a consequence, intravascular pharmacokinetic studies were not performed in man.
Pharmacokinetic studies in different species of laboratory animals were not conducted.
Fibrin sealants/hemostatics are metabolized in the same way as endogenous fibrin by fibrinolysis and phagocytosis.
Toxicology: Preclinical safety data: Due to its nature as well as its special method of application (usually single, only in exceptional cases repeated application of a few mL) and mechanism of action (local efficacy without systemic effect or distribution to other organs and tissues), no preclinical safety data are available for TISSEEL Fibrin Sealant with Synthetic Aprotinin on chronic toxicity, carcinogenicity, reproductive and developmental toxicity or immune stimulation.
Single-dose toxicity studies in rats and rabbits indicated no acute toxicity of TISSEEL Fibrin Sealant with Synthetic Aprotinin. Furthermore, no evidence for mutagenicity could be seen inappropriate in vitro tests. The sealer protein solution was also well tolerated in vitro, in human fibroblast cultures, demonstrating excellent cellular compatibility and non-cytotoxicity. Based on a detailed literature review, any negative influence or toxicity due to residual S/D reagents on TISSEEL Fibrin Sealant with Synthetic Aprotinin can be excluded.

Supportive treatment where standard surgical techniques appear insufficient (see Pharmacology: Pharmacodynamics under Actions): For improvement of hemostasis.
As a tissue glue to improve wound healing or to support sutures in vascular surgery and in gastrointestinal anastomoses.
For tissue sealing, to improve adhesion of the separated tissue (e.g. tissue flaps, grafts, split skin grafts [mesh grafts]).
The efficacy in fully heparinized patients has been proven.

The use of TISSEEL Fibrin Sealant with Synthetic Aprotinin is restricted to experienced surgeons who have been trained in the use of TISSEEL Fibrin Sealant with Synthetic Aprotinin.
Posology: The amount of TISSEEL Fibrin Sealant with Synthetic Aprotinin to be applied and the frequency of application should always be oriented towards the underlying clinical needs of the patient.
The dose to be applied is governed by variables including the type of surgical intervention, the size of the affected area, and the mode of intended application, and the number of applications.
Application of the product must be individualized by the treating physician. In clinical trials, the individual dosages have typically ranged from 4 to 20 mL. For some procedures (e.g. liver traumata, or the sealing of large burned surfaces), larger volumes may be required.
The initial amount of the product to be applied at a chosen anatomic site or target surface area should be sufficient to entirely cover the intended application area. The application can be repeated, if necessary. However, avoid reapplication of TISSEEL Fibrin Sealant with Synthetic Aprotinin to a pre-existing polymerized TISSEEL Fibrin Sealant with Synthetic Aprotinin layer as TISSEEL Fibrin Sealant with Synthetic Aprotinin will not adhere to a polymerized layer.
As a guideline for the gluing of surfaces, 1 pack of TISSEEL Fibrin Sealant with Synthetic Aprotinin 2 mL (i.e. 1 mL TISSEEL Fibrin Sealant with Synthetic Aprotinin solution plus 1 mL thrombin solution) will be sufficient for an area of at least 10 cm².
When TISSEEL Fibrin Sealant with Synthetic Aprotinin is applied by spray application the same quantity will be sufficient to coat considerably larger areas, depending on the specific indication and the individual case.
It is recommended that, to avoid the formation of excess granulation tissue and to ensure gradual absorption of the solidified fibrin sealant, as thin a layer as possible of TISSEEL Fibrin Sealant with Synthetic Aprotinin should be applied.
Paediatric population: The safety and efficacy of TISSEEL Fibrin Sealant with Synthetic Aprotinin in paediatric patients have not been established.
Method of administration: For epilesional use.
In order to ensure optimal safe use of TISSEEL Fibrin Sealant with Synthetic Aprotinin by spray application the following recommendations should be followed: In open wound surgery - a pressure regulator device that delivers a maximum pressure of no more than 2.0 bar (28.5 psi) should be used.
In minimally invasive/laparoscopic procedures - a pressure regulator device that delivers a maximum pressure of no more than 1.5 bar (22 psi) and uses carbon dioxide gas only should be used.
Prior to applying TISSEEL Fibrin Sealant with Synthetic Aprotinin the surface area of the wound needs to be dried by standard techniques (e.g. intermittent application of compresses, swabs, use of suction devices). Do not use pressurized air or gas for drying the site.
TISSEEL Fibrin Sealant with Synthetic Aprotinin must be sprayed only onto application sites that are visible.
TISSEEL Fibrin Sealant with Synthetic Aprotinin should only be reconstituted and administered according to the instructions and with the devices recommended for this product (see Special precautions for disposal and other handling under Cautions for Usage).
For spray application, see Precautions and Special precautions for disposal and other handling under Cautions for Usage for specific recommendations on the required pressure and distance from tissue per surgical procedure and length of applicator tips.
In surgical procedures that require the use of minimal volumes of fibrin sealant, it is recommended to expel and discard the first few drops of product.

No case of overdose has been reported.

TISSEEL Fibrin Sealant with Synthetic Aprotinin alone is not indicated for the treatment of massive and brisk arterial or venous bleeding.
TISSEEL Fibrin Sealant with Synthetic Aprotinin is not indicated to replace skin sutures intended to close surgical wound.
TISSEEL Fibrin Sealant with Synthetic Aprotinin must never be applied intravascularly. Intravascular application may result in life-threatening thromboembolic events.
TISSEEL Fibrin Sealant with Synthetic Aprotinin must not be applied in case of hypersensitivity to the active substances or to any of the excipients.

For epilesional use only. Do not apply intravascularly.
Life threatening thromboembolic complications may occur if the preparation is unintentionally applied intravascularly.
Caution must be used when applying fibrin sealant using pressurized gas.
Any application of pressurized gas is associated with a potential risk of air or gas embolism, tissue rupture, or gas entrapment with compression, which may be life-threatening.
Apply TISSEEL Fibrin Sealant with Synthetic Aprotinin as a thin layer. Excessive clot thickness may negatively interfere with the product's efficacy and the wound healing process.
Life-threatening/fatal air or gas embolism has occurred with the use of spray devices employing a pressure regulator to administer fibrin sealants. This event appears to be related to the use of the spray device at higher than recommended pressures and/or in close proximity to the tissue surface. The risk appears to be higher when fibrin sealants are sprayed with air, as compared to CO₂ and therefore cannot be excluded with TISSEEL Fibrin Sealant with Synthetic Aprotinin when sprayed in open wound surgery.
When applying TISSEEL Fibrin Sealant with Synthetic Aprotinin using a spray device, be sure to use a pressure within the pressure range recommended by the spray device manufacturer (see table in Special precautions for disposal and other handling under Cautions for Usage for pressures and distances).
TISSEEL Fibrin Sealant with Synthetic Aprotinin spray application should only be used if it is possible to accurately judge the spray distance as recommended by the manufacturer. Do not spray closer than the recommended distances.
When spraying TISSEEL Fibrin Sealant with Synthetic Aprotinin, changes in blood pressure, pulse, oxygen saturation and end tidal CO₂ should be monitored because of the possibility of occurrence of air or gas embolism (also see Dosage & Administration).
TISSEEL Fibrin Sealant with Synthetic Aprotinin must not be used with the Easy Spray/Spray Set system in enclosed body areas.
Before the administration of TISSEEL Fibrin Sealant with Synthetic Aprotinin, care is to be taken that parts of the body outside the designated application area are sufficiently protected/covered to prevent tissue adhesion at undesired sites.
If fibrin sealants are applied in confined spaces, e.g. the brain or the spinal cord, the risk of compressive complications should be taken into account.
To ensure adequate mixing of the sealer protein component and the thrombin component, the first few drops of the product from the application cannula should be expelled and discarded immediately before use.
As with any protein-containing product, allergic type hypersensitivity reactions are possible.
Intravascular application might increase the likelihood and severity of acute hypersensitivity reactions in susceptible patients.
Hypersensitivity and anaphylactic reactions (also fatal, including anaphylactic shock) have been reported with TISSEEL Fibrin Sealant with Synthetic Aprotinin. Signs of hypersensitivity reactions may include hives, generalized urticaria, tightness of the chest, wheezing, hypotension. If these symptoms occur, the administration must be discontinued immediately and the currently valid standard measures for the treatment of shock are to be taken.Remaining product must be removed from the site of application.
TISSEEL Fibrin Sealant with Synthetic Aprotinin contains a synthetic protein (aprotinin). Even in case of strict local application, there is a risk of anaphylactic reaction linked to the presence of aprotinin. The risk seems to be higher in cases where there was previous exposure, even if it was well tolerated. Therefore, any use of aprotinin or aprotinin containing products should be recorded in the patients' records.
As synthetic aprotinin is structurally identical to bovine aprotinin the use of TISSEEL Fibrin Sealant with Synthetic Aprotinin in patients with allergies to bovine proteins should be carefully evaluated.
In two retrospective, non-randomized studies in coronary bypass surgery, patients who received fibrin sealant showed a statistically significant increased risk of mortality. While these studies could not provide a causal relationship, the increased risk associated with the use of TISSEEL Fibrin Sealant with Synthetic Aprotinin in these patients cannot be excluded. Therefore, additional care should be taken to avoid inadvertent intravascular administration of this product.
Injection into the nasal mucosa must be avoided, as thromboembolic complications may occur in the area of the arteria ophthalmica.
Injecting TISSEEL Fibrin Sealant with Synthetic Aprotinin into tissue carries the risk of local tissue damage.
TISSEEL Fibrin Sealant with Synthetic Aprotinin should only be applied as a thin layer. Excessive clot thickness may negatively interfere with the product's efficacy and the wound healing process.
Polysorbate 80 may cause locally limited skin irritations such as contact dermatitis.
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
These measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), and for the non-enveloped hepatitis A virus (HAV).
The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection may be serious for pregnant women (fetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g., hemolytic anemia).
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated receipt of human plasma-derived fibrin sealant.
It is strongly recommended that every time that TISSEEL Fibrin Sealant with Synthetic Aprotinin is administered to the patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
Oxidized cellulose-containing preparations should not be used with TISSEEL Fibrin Sealant with Synthetic Aprotinin (see Incompatibilities under Cautions for Usage).
Effects on ability to drive and use machines: Not relevant.

The safety of fibrin sealants/hemostatics for use in human pregnancy or breastfeeding has not been established in controlled clinical trials. Experimental animal studies are insufficient to assess the safety with respect to reproduction, development of the embryo or fetus, the course of gestation and peri-and postnatal development.
Therefore, the product should be administered to pregnant and lactating women only if clearly needed.
See Precautions for information on Parvovirus B19 infection.

Hypersensitivity or allergic reactions (which may include but are not limited to angioedema, burning and stinging at the application site, bradycardia, bronchospasm, chills, breathing difficulties, transient erythema ("flushing"), generalized urticaria, headache, hives, hypotension, lethargy, nausea, pruritus, restlessness, paresthesia, tachycardia, tightness of the chest, tingling, vomiting, wheezing) may occur in rare cases in patients treated with fibrin sealants/hemostatics, anaphylactic reactions and anaphylactic shock have included fatal outcomes.
In isolated cases, these reactions have progressed to severe anaphylaxis. Such reactions may especially be seen if the preparation is applied repeatedly, or administered to patients known to be hypersensitive to aprotinin (see Precautions) or any other constituents of the product.
Even if repeated treatment with TISSEEL Fibrin Sealant with Synthetic Aprotinin was well tolerated, a subsequent administration of TISSEEL Fibrin Sealant with Synthetic Aprotinin or systemic administration of aprotinin may result in severe anaphylactic reactions.
Antibodies against components of the fibrin sealant/hemostatic may occur in rare cases.
Inadvertent intravascular injection may result in thromboembolic events and DIC.
Furthermore, there is the risk of an anaphylactic reaction (see Precautions).
For safety with respect to transmissible agents, see Precautions.
The adverse reactions presented in this monograph were reported from clinical trials investigating the safety and efficacy of TISSEEL Fibrin Sealant with Synthetic Aprotinin and from post-marketing experience (marked with a ^p in the adverse event table as follows) with Baxter Fibrin Sealants. In the clinical trials, TISSEEL Fibrin Sealant with Synthetic Aprotinin was administered for adjunct hemostasis in cardiac, vascular, and total hip replacement surgeries and in liver and spleen surgeries. Other clinical trials included the sealing of lymphatic vessels in patients undergoing axillary lymph node dissection, sealing of colonic anastomosis and in dural sealing in the posterior fossa. As the frequencies of adverse events observed in post-marketing experience cannot be calculated, whenever possible, the upper limit of the 95% confidence interval was calculated using the "rule of three" in the following manner: 3/1146=0.0026 or 0.26% which is "Uncommon" (where "1146" is the total number of subjects to have received TISSEEL Fibrin Sealant with Synthetic Aprotinin in the clinical trials from which data were included in the monograph).
Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data). (See Table 2.)

Click on icon to see table/diagram/image

Class Reactions: Other adverse reactions associated with the fibrin sealant/hemostatic class include: manifestations of hypersensitivity include application site irritation, chest discomfort, chills, headache, lethargy, restlessness, and vomiting.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

No interaction studies have been performed. Similar to comparable products or thrombin solutions, the product may be denatured after exposure to solutions containing alcohol, iodine or heavy metals (e.g. antiseptic solutions). Such substances should be removed to the greatest possible extent before applying the product.
See Incompatibilities under Cautions for Usage.

Incompatibilities: Oxidized cellulose-containing preparations should not be used with TISSEEL Fibrin Sealant with Synthetic Aprotinin because the low pH interferes with the activity of the thrombin.
This medicinal product must not be mixed with other medicinal products except those mentioned in Special precautions for disposal and other handling as follows.
Special precautions for disposal and other handling: General: Before the administration of TISSEEL Fibrin Sealant with Synthetic Aprotinin, cover all parts of the body outside the area to be treated in order to prevent tissue adhesion at undesired sites.
To prevent TISSEEL Fibrin Sealant with Synthetic Aprotinin from adhering to gloves and instruments, wet these with sodium chloride solution before contact.
The guideline for sealing surfaces is: One package of TISSEEL Fibrin Sealant with Synthetic Aprotinin 2 mL (i.e. 1 mL sealer protein solution plus 1 mL thrombin solution) is sufficient for a surface of at least 10 cm².
The dose required depends on the size of the surface to be sealed.
Do not apply the two components of TISSEEL Fibrin Sealant with Synthetic Aprotinin separately. Both components must be applied together.
Do not expose TISSEEL Fibrin Sealant with Synthetic Aprotinin to temperatures above 37°C. Do not microwave.
Do not thaw the product by holding it in the hands.
Do not use TISSEEL Fibrin Sealant with Synthetic Aprotinin until it is completely thawed and warmed to 33°C-37°C.
Remove the protective cap of the syringe only when thawing and warming is complete.
For PRIMA syringe: To facilitate removal of the tip cap from the syringe, rock the tip cap by moving it backward and forward, then pull the protective cap off the syringe.
Expel all air from the syringe then attach the joining piece and application cannula.
Instructions for handling and preparation: Both the sealer protein solution and the thrombin solution are contained in a ready-to-use syringe. The product is packed in two sterile bags under aseptic conditions. The inner bag and its contents are sterile as long as the outer bag remains intact. Using sterile technique, transfer the sterile inner pouch and contents onto the sterile field.
The ready-to-use syringe may be thawed and warmed using one of the following methods: 1. Rapid thawing/warming (sterile water bath) - Recommended method. 2. Thawing/warming in a non-sterile water bath; 3. Thawing/warming in an incubator. 4. The ready-to-use syringe may also be thawed and kept at room temperature (not above 25°C) for up to 72 hours. Warming is required prior to use.
1) Rapid thawing/warming (sterile water bath) - Recommended method: It is recommended to thaw and warm the two sealant components using a sterile water bath at a temperature of 33-37°C.
The water bath must not exceed a temperature of 37°C. In order to monitor the specified temperature range, control the water temperature using a thermometer and change the water as necessary.
When using a sterile water bath for thawing and warming, remove the pre-filled syringe from the bags before placing it in the sterile water bath.
Instructions: Bring the inner bag into the sterile area, remove the ready-to-use syringe from the inner bag and place it directly in the sterile water bath. Ensure that the content of the ready-to-use syringe is completely immersed in the water. (See Table 3.)

Click on icon to see table/diagram/image

2) Thawing/warming in a non-sterile water bath: Instructions: Leave the ready-to-use syringe inside both bags and place it in a water bath outside the sterile area for the appropriate length of time (see Table 4). Ensure that the bags remain immersed in the water during the entire thawing time. After thawing, remove the bags from the water bath, dry the outer bag and bring the inner bag with the ready-to-use syringe into the sterile area. (See Table 4.)

Click on icon to see table/diagram/image

3) Thawing/warming in an incubator: Instructions: Leave the ready-to-use syringe inside both bags and place it in an incubator outside the sterile area for the appropriate length of time (see Table 5). After thawing/warming, remove the bags from the incubator, remove the outer bag and bring the inner bag with the ready-to-use syringe into the sterile area. (See Table 5.)

Click on icon to see table/diagram/image

4) Thawing at room temperature (not above 25°C) before warming: Instructions: Leave the ready-to-use syringe inside both bags and thaw it at room temperature outside the sterile area for the appropriate length of time (see Table 6). Once thawed, in order to warm the product for use, warm it in the outer bag in an incubator. (See Table 6.)

Click on icon to see table/diagram/image

After thawing at room temperature, the product and must be used within 72 hours of removing from the freezer.
Stability after thawing: After thawing and warming (at temperatures between 33°C and 37°C, methods 1, 2 and 3), chemical and physical product stability has been demonstrated for 12 hours at 33°C to 37°C. For product thawed at room temperature in the unopened bag (method 4), chemical and physical product stability has been demonstrated for 72 hours at temperatures no more than 25°C. Warm to 33°C to 37°C immediately before use.
From a microbiological point of view, unless the method of opening/thawing precludes the risks of microbial contamination, the product should be used immediately after being warmed to 33°C to 37°C.
If not used immediately, in-use storage times and conditions are the responsibility of the user.
Do not re-freeze or refrigerate once thawing has been initiated.
Handling after thawing/before application: To achieve optimal blending of the two solutions and optimal solidification of the fibrin sealant, maintain the two sealant components at 33°C-37°C until application.
The sealer protein and the thrombin solutions should be clear or slightly opalescent. Do not use solutions that are cloudy or have deposits. Before use, check the thawed product visually for particles, discoloration or other changes in its appearance. If one of the above occurs, dispose of the solutions.
The thawed sealer protein solution should be liquid but slightly viscous. If the solution has the consistency of a solidified gel, it must be assumed to have become denatured (possibly due to an interruption of the cold storage chain or by overheating during warming). In this case, do not use TISSEEL Fibrin Sealant with Synthetic Aprotinin on any account: Remove the syringe from the bags shortly before use.
Use TISSEEL Fibrin Sealant with Synthetic Aprotinin only when it is thawed and warmed completely (liquid consistency).
Remove the protective cap from the syringe immediately before application.
For PRIMA syringe: To facilitate removal of the tip cap from the syringe, rock the tip cap by moving it backward and forward, then pull the protective cap off the syringe.
Administration with PRIMA Syringe: For application, connect the double chamber ready-to-use syringe with the sealer protein solution and the thrombin solution to a joining piece and an application cannula - both are provided in the set with the application devices. The common plunger of the double chamber ready-to-use syringe ensures that equal volumes of the two sealant components are fed through the joining piece into the application cannula where they are blended and then applied.
Operating instructions for PRIMA Syringe: Expel all air from the syringe prior to attaching any application device.
Align the joining piece and tether to the side of the syringe with the tether strap hole.
Connect the nozzles of the double chamber ready-to-use syringe to the joining piece, ensuring that they are firmly attached.
Secure the joining piece by fastening the tether strap to the double chamber ready-to-use syringe.
If the tether strap tears, use the spare joining piece provided in the kit.
If a spare joining piece is not available, the system can still be used if care is taken to ensure that the connection is secure and leak-proof.
Do not expel the air remaining inside the joining piece.
Attach an application cannula on to the joining piece.
Do not expel the air remaining inside the joining piece and inside the application cannula until the patient starts the actual application because this may clog the application cannula.
Administration: Prior to applying TISSEEL Fibrin Sealant with Synthetic Aprotinin the surface of the wound needs to be dried by standard techniques (e.g. intermittent application of compresses, swabs, use of suction devices). Do not use pressurized air or gas for drying the site.
Apply the mixed sealer protein-thrombin solution on to the recipient surface or on to the surfaces of the parts to be glued by slowly pressing on the back of the common plunger.
In surgical procedures that require the use of minimal volumes of fibrin sealant, it is recommended to expel and discard the first few drops of product.
After TISSEEL Fibrin Sealant with Synthetic Aprotinin has been applied, allow at least 2 minutes to achieve sufficient polymerization.
Or
Administration with AST Syringe: For application, connect the double chamber ready-to-use syringe with the sealer protein solution and the thrombin solution to a joining piece and an application cannula - both are provided in the set with the application devices. The common plunger of the double chamber ready-to-use syringe, likewise provided in the set with the application devices, ensures that equal volumes of the two sealant components are fed through the joining piece into the application cannula where they are blended and then applied.
Operating instructions for AST Syringe: Expel all air from the syringe prior to attaching any application device.
Align the joining piece and tether to the side of the syringe with the tether strap hole.
Connect the nozzles of the double chamber ready-to-use syringe to the joining piece ensuring that they are firmly attached.
Secure the joining piece by fastening the tether strap to the double chamber ready-to-use syringe.
If the tether strap tears, use the spare joining piece provided in the kit.
If a spare joining piece is not available, the system can still be used if care is taken to ensure that the connection is secure and leak-proof.
Do not expel the air remaining inside the joining piece.
Attach an application cannula on to the joining piece.
Do not expel the air remaining inside the joining piece and inside the application cannula until the patient starts the actual application because this may clog the application cannula.
Administration: Prior to applying TISSEEL Fibrin Sealant with Synthetic Aprotinin the surface of the wound needs to be dried by standard techniques (e.g. intermittent application of compresses, swabs, use of suction devices). Do not use pressurized air or gas for drying the site.
Apply the mixed sealer protein-thrombin solution on to the recipient surface or on to the surfaces of the parts to be glued by slowly pressing on the back of the common plunger; In surgical procedures that require the use of minimal volumes of fibrin sealant, it is recommended to expel and discard the first few drops of product; After TISSEEL Fibrin Sealant with Synthetic Aprotinin has been applied, allow at least 2 minutes to achieve sufficient polymerization.
Or
Administration with Duo Syringe System: For application, connect the two single use syringes with the sealer protein solution and with the thrombin solution to a joining piece and an application cannula as provided in the accompanying Set of Devices (DUPLOJECT COMBI). The common plunger of the DUPLOJECT Two-Syringe Clip ensures that equal volumes are fed through the joining piece into the application cannula where they are blended and then applied.
Operating instructions for Duo Syringe System: Expel all air from the syringe prior to attaching any application device.
Align the joining piece and tether to the side of the syringe with the tetherstrap attachment point.
Connect the nozzles of the Duo Syringe System to the joining piece ensuring that theyare firmly attached.
Secure the joining piece by fastening the tether strap to the DUPLOJECT Two-Syringe Clip.
If the tether strap tears, use the spare joining piece provided in the kit.
If a separate joining piece is not available, the system can still be used if care is taken to ensure that the connection is secure and leak-proof.
Do not expel the air remaining inside the joining piece.
Attach an application cannula on to the joining piece.
Do not expel the air remaining inside the joining piece and inside the application cannula until the patient starts the actual application because this may clog the application cannula.
Administration: Prior to applying TISSEEL Fibrin Sealant with Synthetic Aprotinin the surface of the wound needs to be dried by standard techniques (e.g. intermittent application of compresses, swabs, use of suction devices). Do not use pressurized air or gas for drying the site.
Apply the mixed sealer protein - thrombin solution on to the recipient surface or on to the surfaces of the parts to be glued by slowly pressing on the back of the common plunger.
In surgical procedures that require the use of minimal volumes of fibrin sealant, it is recommended to expel and discard the first few drops of product.
After TISSEEL Fibrin Sealant with Synthetic Aprotinin has been applied, allow at least 2 minutes to achieve sufficient polymerization.
Note: If application of the fibrin sealant components is interrupted, clogging may occur in the cannula. In this case, replace the application cannula with a new one immediately before application is resumed. If the openings of the joining piece are clogged, use the spare joining piece provided in the package.
After blending of the sealant components, the fibrin sealant starts to set within seconds due to the high thrombin concentration (500 IU/mL).
The fibrin sealant can also be applied with other accessories supplied by BAXTER which are particularly suited, for example, for endoscopic use, minimally invasive surgery or application to large or difficult-to-access areas. When using these application devices, please follow their instructions for use carefully.
In certain applications, biocompatible material, such as collagen fleece, is used as a carrier substance or for reinforcement.
Spray application: When applying TISSEEL Fibrin Sealant with Synthetic Aprotinin using a spray device be sure to use a pressure and a distance from tissue within the ranges recommended by the manufacturer as follows: see Table 7.

Click on icon to see table/diagram/image

When spraying TISSEEL Fibrin Sealant with Synthetic Aprotinin, changes in blood pressure, pulse, oxygen saturation and end tidal CO₂ should be monitored because of the possibility of occurrence of air or gas embolism (see Dosage & Administration and Precautions).
For the application of TISSEEL Fibrin Sealant with Synthetic Aprotinin in enclosed thoracic and abdominal spaces the DuploSpray MIS applicator and regulator system is recommended. Please refer to the instruction manual of the DuploSpray MIS device.
Disposal: Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Store and transport frozen (at ≤-20°C) without interruption until application.
Store in the original package in order to protect from light.
The unopened product, thawed at up to 25°C, may be stored at not more than 25°C for up to 72 hours. If the solution is not used within 72 hours after thawing, dispose of TISSEEL Fibrin Sealant with Synthetic Aprotinin.
Do not re-freeze or refrigerate the thawed solution on any account.
Shelf life: 2 years.

Haemostatics

B02BC30 - combinations ; Belongs to the class of local hemostatics. Used in the treatment of hemorrhage.

D