What it is and what it is used for

for

What TISSEEL is The name of your medicine is TISSEEL Ready to use. Throughout this leaflet TISSEEL Ready to use will be called TISSEEL. TISSEEL is a two-component tissue sealant, and it contains two of the proteins that make blood clot. These proteins are called fibrinogen and thrombin. When these proteins mix during application, they form a clot where the surgeon applies them. TISSEEL is prepared as two solutions (Sealer Protein Solution and Thrombin Solution), which mix when applied. What TISSEEL is used for TISSEEL is a fibrin or tissue sealant. During surgery, tissues may bleed and it may not be possible for the surgeon to control this bleeding using stitches, or by applying pressure. TISSEEL is applied to the surface of tissues, either to control bleeding, or to stop (or prevent) leaks of other types of fluid, by creating a watertight seal. TISSEEL can be used even if your blood does not clot properly, e.g. when you are being treated with heparin against thrombosis. It is also used as a tissue glue to achieve adhesion/sealing or as suture support in surgery. In addition, TISSEEL is used to fix mesh during hernia repair surgery.

The clot produced by TISSEEL is very similar to a natural blood clot and this means that it will dissolve naturally and leave no residue. However, aprotinin is added to increase the longevity of the clot and to prevent its premature dissolution. 2.

What you need to know before you take it

e TISSEEL

Do not use TISSEEL in the following situations: • •

•

TISSEEL must not be used for massive or brisk bleeding. TISSEEL MUST NOT be injected into blood vessels (veins or arteries), or into tissues. As TISSEEL forms a clot where it is applied, injecting TISSEEL may cause serious reactions. TISSEEL should only be applied to the surface of tissues as a thin layer where it is needed. If you are going to have a coronary bypass surgery, special care needs to be taken to avoid injecting TISSEEL into blood vessels If you are allergic ( hypersensitive ) to any of the active substances or any of the other ingredients of this medicine. TISSEEL contains a synthetic protein, called aprotinin. Even when this protein is applied in small areas, there is a risk of a reaction known as anaphylaxis, or a severe allergic (hypersensitive) reaction.

Take special care with TISSEEL •

• • • •

•

Life-threatening/fatal air or gas embolism (air getting into the blood circulation which can be serious or life-threatening) has occurred very rarely with the use of spray devices employing pressure regulators to administer fibrin sealants. This 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 when sprayed in open wound surgery. Spray devices and the accessory tip provide instructions for use with recommendations for pressure ranges and to the spraying distance from the tissue surface. TISSEEL should be administered strictly according to the instructions and only with devices recommended for this product. When spraying TISSEEL, changes in blood pressure, pulse, oxygen saturation and end tidal CO2 should be monitored for possible occurrence of gas embolism. If you have ever received TISSEEL or aprotinin before, your body may have become sensitive to it. It is possible you may be allergic to this material, even if there was no reaction to the first application. If you think you have received either product in a previous operation, you have to inform your doctor about this. If the surgeon or operating team sees any sign of an allergic reaction during the application of TISSEEL, they will stop using TISSEEL immediately and will take the adequate measures.

Other medicines and TISSEEL There are no known interactions between TISSEEL and other medicinal products. Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Oxidised cellulose containing preparations may reduce the efficacy of TISSEEL and should not be used as carrier materials. TISSEEL with food and drink Please ask your doctor. Your doctor will decide if you are allowed to eat and drink before the application of TISSEEL. Pregnancy, breast-feeding and fertility If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your doctor will decide if you can use TISSEEL during pregnancy or breast-feeding. Driving and using machines TISSEEL will not affect your ability to drive or operate other types of machines. Important information about some of the ingredients of TISSEEL Polysorbate 80 may cause locally limited skin irritations such as contact dermatitis. Important information about the potential risk of infection from donor human plasma When medicines are made from human blood or plasma, certain steps are taken to prevent infections being passed on to patients. Blood and plasma donors are carefully selected to make sure that those at risk of carrying infections are excluded. In addition, each donation and plasma pool is tested for signs of viruses or infections. Manufacturers of these products also include steps in the processing of the blood or plasma that can inactivate or remove viruses. Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging viruses or other types of infections. 3.

How to take it

TISSEEL

•

TISSEEL is only applied during a surgical operation. The use of TISSEEL is restricted to experienced surgeons who have been trained in the use of TISSEEL. The amount of TISSEEL that will be used depends on a number of factors, including but not limited to the type of surgery, the surface area of tissue to be treated during your operation and the way TISSEEL is applied. The surgeon will decide how much is appropriate, and will apply just enough to form a thin, even layer over the tissue. If this does not seem to be enough, a second layer can be applied. However, avoid a reapplication of TISSEEL to a pre-existing polymerized TISSEEL layer as TISSEEL will not adhere to a polymerized layer. Separate, sequential application of the two components of TISSEEL must be avoided.

• •

During your operation, the surgeon will apply TISSEEL onto the relevant tissue surface, using the special application device provided. This device ensures that equal amounts of both components are applied at the same time – which is important for the optimal effect of TISSEEL. For hernia repair surgery the surgeon will apply Tisseel using spray or drops to fix the mesh in place.

• • •

Prior to applying TISSEEL the surface area of the wound needs to be dried by standard techniques (e.g. intermittent application of compresses, swabs, use of suction devices). Pressurised air or gas must not be used for drying the site. TISSEEL must be sprayed only onto application sites that are visible.

When applying TISSEEL using a spray device be sure to use a pressure and a distance from the tissue within the range recommended by the manufacturer as follows: Recommended pressure, distance and devices for spray application of TISSEEL Surgery

Open wound

Laparoscopic/ minimally invasive procedures

Spray set to be used Tisseel / Artiss Spray Set Tisseel / Artiss Spray Set 10 pack

n.a.

Applicator tips to be used

Pressure regulator to be used

n.a.

EasySpray

n.a.

EasySpray

Duplospray MIS Applicator 20 cm Duplospray MIS Applicator 30 cm Duplospray MIS Applicator 40 cm Spray Set 360 Endoscopic Applicator with Snaplock Spray Set 360 Endoscopic Applicator with Tether Replaceable tip

Duplospray MIS Regulator 1.5 bar

Recommended distance from target tissue

Recommended spray pressure

10-15cm

1.5-2.0 bar (21.8-29.0 psi).

2-5 cm

1.2-1.5 bar (18-22 psi)

When spraying TISSEEL, 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 section 2). If you take more TISSEEL than you should TISSEEL is only applied during a surgical operation. It is applied by the surgeon and the amount of TISSEEL is determined by the surgeon. If you have any further questions on the use of this product, ask your doctor or pharmacist. Use in children Safety and efficacy of the product in children have not been established. 4.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If any of the

Possible side effects

gets serious or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In patients who are treated with fibrin sealant, hypersensitivity reactions or allergic reactions may occur. These side effects may be severe. The first signs of an allergic reaction may include –

transient reddening of the skin ("flushing")

–

itching

–

hives

–

nausea, vomiting

–

headache

–

drowsiness

–

restlessness

–

burning and stinging at the application site

–

tingling

–

chills

–

tightness of the chest

–

swelling of lips, tongue, throat (which may result in difficulty to breathe and/or swallow)

–

breathing difficulties

–

low blood pressure

–

increase or drop in pulse rate

–

loss of consciousness due to a drop in blood pressure

In isolated cases, these reactions may progress to severe allergic reactions (anaphylaxis). Such reactions may be seen especially if the preparation is applied repeatedly or administered to patients who have previously shown hypersensitivity to aprotinin or any other component of the product. Even if repeated treatment with TISSEEL was well tolerated, a subsequent administration of TISSEEL or an infusion of aprotinin may result in severe allergic (anaphylactic) reactions. The attending surgical team is well aware of the risk of reactions of this type and will immediately interrupt the application of TISSEEL on the occurrence of the first signs of hypersensitivity. In the case of severe symptoms emergency measures may be required. The injection of TISSEEL into soft tissues may lead to local tissue damage. If TISSEEL is accidentally injected inside blood vessels (veins or arteries) may lead to the formation of blood clots (thromboses). As TISSEEL is derived from plasma from blood donations, the risk of an infection cannot be excluded completely. However, the manufacturers take numerous measures to reduce this risk (see section 2). Antibodies against components of the fibrin sealant may occur in rare cases. The following side effects have been observed in treatment with TISSEEL: Common (may affect up to 1 in 10 people) –

Postoperative wound infection

–

Sensory disturbance

–

Axillary venous thrombosis

–

Skin Rash

–

Pain in extremities

Uncommon (may affect up to 1 in 100 people) –

Increase of fibrin degradation products

–

Nausea

Rare (may affect up to 1 in 1,000 people) –

Drop in blood pressure

Not known (frequency cannot be estimated from the available data) –

Hypersensitivity reactions

–

Allergic (anaphylactic) reactions

–

Anaphylactic shock

–

Sensation of tingling, pricking or numbness of the skin

–

Tightness of the chest

–

Breathing difficulties

–

Itching

–

Reddening of the skin

–

Increase or drop in pulse rate

–

Bruising

–

Gas bubbles in the vascular system*

–

Blood clot in blood vessels

–

Blockage of an artery in the brain

–

Dyspnoea

–

Intestinal obstruction

–

Hives

–

Impaired healing

• the introduction of air or gas bubbles in the vascular system have occurred when fibrin sealants are applied with devices using pressurized air or gas; this is believed to be caused by inappropriate use of the spray device (e.g. at higher than recommended pressure and in close proximity to the tissue surface.) Reporting side effects If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcardor search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects you can help provide more information on the safety of this medicine.

How to store it

TISSEEL • • • • 6.

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the container after "EXP". Store at ≤ -20°C (in a freezer). The cold storage chain must not be interrupted until use. After thawing, the solution must not be refrozen or refrigerated.

Contents of the pack and other information

What TISSEEL contains TISSEEL consists of two components: Component 1 = Sealer protein solution The active substances in 1 ml sealer protein solution are: human fibrinogen, 91 mg/ml; aprotinin, 3000 KIU/ml. The other ingredients are: human albumin, L-histidine, niacinamide, polysorbate 80 (Tween 80), sodium citrate dihydrate, Water for Injections. Component 2 = Thrombin Solution: The active substances contained in 1 ml of the Thrombin Solution are: Human Thrombin, 500 IU/ml; Calcium Chloride Dihydrate, 40 μmol/ml. The excipients are Human Albumin, Sodium Chloride and Water for Injections. What TISSEEL looks like and the contents of the pack Solutions for sealant. TISSEEL is supplied in a pre-filled single-use double chamber syringe closed with a tip cap packed in two pouches (outer and inner pouch) and one device set with 2 joining pieces and 4 application cannulas. Both components are colourless or pale yellow. TISSEEL is available in the following pack sizes of 1 syringe: 2 ml (1 ml of human fibrinogen and 1 ml of human thrombin) 4 ml (2 ml of human fibrinogen and 2 ml of human thrombin) 10 ml (5 ml of human fibrinogen and 5 ml of human thrombin) Not all pack sizes may be marketed. Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder: Baxter Healthcare Caxton Way, Thetford, Norfolk, IP24 3SE, UK Manufacturer Takeda Manufacturing Austria AG Industriestraße 67 A-1221 Vienna Austria This leaflet was last revised in 01/2026 __________________________________________________________________________________

The following information is intended for medical or healthcare professionals only: General

• The inner pouch and its contents are sterile unless the integrity of the outer pouch is compromised. •

The sealer protein and the thrombin solutions should be clear or slightly opalescent.

•

Do not use solutions that are cloudy, discolored, have deposits or other changes in their appearance, including the consistency of a solidified gel after thawing.

•

Before the application of TISSEEL, ensure that all parts of the body outside the desired application area are sufficiently covered, to prevent tissue adhesion at undesired sites.

•

Some solutions that contain alcohol, iodine or certain types of metals (these are normally found in disinfectants or antiseptics) may reduce the ability of TISSEEL to work normally. These substances should be removed, as far as possible, before TISSEEL is applied.

Thawing of the frozen presentation •

Do not use TISSEEL unless it is completely thawed and warmed (liquid to slightly viscous consistency).

• •

TISSEEL must not be exposed to temperatures above 37°C and must not be microwaved. The protective syringe cap should not be removed until thawing and warming is complete and application tip is ready to be attached. 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.

•

Thaw and warm the pre-filled syringes using one of the following options: Option 1: Quick thawing/warming methods (preparation in a single step) a. Sterile Water Bath b. Non-Sterile Water Bath c. Incubator Option 2: Thawing at Room Temperature (not above +25°C) followed by warming in Incubator (possibility of interim storage for up to 72 hours at temperatures not exceeding +25°C) 1) Quick thawing/warming methods An overview of the quick thawing/warming methods is provided in Table 1. Table 1: Quick Thawing /Warming Methods at 33°C – 37°C Minimum Thawing/Warming Times Pack Size

Sterile Water Bath (Pouches Removed)

Non-Sterile Water Bath (In Pouches)

Incubator (In Pouches)

2 ml

5 min

15 min

40 min

4 ml

5 min

20 min

50 min

10 ml

10 min

35 min

90 min

Note: If a water bath is used it must not exceed the temperature of +37°C.

a) Sterile Water Bath (Recommended Method) •

Remove the outer pouch and transfer the pre-filled syringe packed in the inner pouch, into the sterile area.

•

Remove the pre-filled syringe from the inner pouch and place the syringe directly into the sterile water heated to 33°C – 37°C ensuring the syringe is completely immersed in the water (See Table 1 for minimum thawing/warming times).

• To monitor the specified temperature range, control the water temperature using a thermometer and change the water as necessary.

b) Non-Sterile Water Bath •

Place the pre-filled syringe packed in both pouches, in a water bath heated to 33°C – 37°C outside the sterile area, ensuring the pouches remain immersed in the water (See Table 1 for minimum thawing/warming times).

•

Remove the pouches from the water bath after thawing and warming. Dry and remove the outer pouch and transfer the pre-filled syringe in the inner pouch, onto the sterile area.

c) Incubator • Place the pre-filled syringe, packed in both pouches, in an incubator outside the sterile area (See Table 1 for minimum thawing/warming times). •

After thawing/warming in the incubator, remove the outer pouch and transfer the pre-filled syringe, inside the inner pouch, into the sterile area.

2) Thawing at room temperature (not above 25°C) followed by warming in incubator •

Thaw the pre-filled syringe, packed in both pouches, at room temperature outside the sterile area (See Table 2 for minimum thawing times).

•

Warm the pre-filled syringe, packed in both pouches, in an incubator at 33°C – 37°C outside the sterile area (See Table 2 for minimum warming times).

•

After thawing/warming in the incubator, remove the outer pouch and transfer the pre-filled syringe, inside the inner pouch, into the sterile area. Table 2: Thawing at Room Temperature and Warming in Incubator Pack Size

Minimum Thawing /Warming Times Warming in Incubator Thawing at room temperature (33-37°C) (Not above 25°C)

2 ml

80 minutes

11 minutes

4 ml

90 minutes

13 minutes

10 ml

160 minutes

25 minutes

Stability after thawing After thawing and warming at temperatures between 33°C – 37°C, (Options 1 and 2), the product must be used within 12 hours.

After thawing at room temperature (Option 2), the product can be stored for up to 72 hours at temperatures not exceeding 25°C, provided it remains sealed in the original package (both pouches). Do not re-freeze or refrigerate once thawing has been initiated. Handling after thawing / before application The product must be warmed to 33°C – 37°C before use. 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 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 on any account. Non-Spray Administration For application, connect the double-chamber 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 syringe ensures that the 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

Double Plunger Tether Strap

Double Chamber Syringe Joining piece Application Cannula • • •

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 double-chamber syringe nozzles to the joining piece ensuring that they are firmly attached. o

Secure the joining piece by fastening the tether strap to the double-chamber syringe.

o

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.

o

Do NOT expel the air remaining inside the joining piece.

o

If the tether strap tears, use the spare joining piece provided in the kit.

• Attach an application cannula on to the joining piece. o Do NOT expel the air remaining inside the joining piece and inside the application cannula until you start the actual application because this may clog the application cannula.

Administration Prior to applying TISSEEL 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 Fibrin Sealer Protein – Thrombin Solution onto the recipient surface or surfaces of the parts to be sealed.
• 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.
• When Tisseel is used for mesh fixation it may be applied as drops and/or by a spray technique depending on the preference of the surgeon. Usually drops of Tisseel are applied where surgeons routinely position staples and the layer of fibrin sealant achieved with spraying allows the entire mesh to be fixed in place without shrinking and folding. Note: If application of the fibrin sealant components is interrupted, clogging occurs immediately in the needle. Only replace the application needle with a new one only immediately before application is resumed. If the apertures of the joining piece are clogged, use the spare joining piece provided in the package. After mixing of the sealant components, the fibrin sealant starts to set within seconds, because of the high Thrombin concentration (500 IU/ml). The fibrin sealant can also be applied with other accessories supplied by BAXTER that are particularly suited for, e.g., endoscopic use, minimally invasive surgery, application to large or difficult-to-access areas. When using these application devices, strictly follow the Instructions for Use of the devices. After the two components have been applied, position the wound areas. Fix or hold the glued parts with continuous gentle pressure in the desired position for about 3-5 minutes to ensure that the setting fibrin sealant adheres firmly to the surrounding tissue. In certain applications biocompatible material, such as collagen fleece, is used as a carrier substance or for reinforcement. Application with Spray Device When applying TISSEEL using a spray device be sure to use a pressure and a distance from the tissue within the range recommended by the manufacturer as follows:

Table 3: Recommended pressure, distance and devices for spray application of TISSEEL Surgery

Open wound

Laparoscopic/ minimally invasive procedures

Spray set to be used Tisseel / Artiss Spray Set Tisseel / Artiss Spray Set 10 pack

n.a.

Applicator tips to be used

Pressure regulator to be used

n.a.

EasySpray

n.a. Duplospray MIS Applicator 20 cm Duplospray MIS Applicator 30 cm Duplospray MIS Applicator 40 cm Spray Set 360 Endoscopic Applicator with Snaplock Spray Set 360 Endoscopic Applicator with Tether

EasySpray

Duplospray MIS Regulator 1.5 bar

Recommended distance from target tissue

Recommended spray pressure

10-15cm

1.5-2.0 bar (21.8-29.0 psi).

2-5 cm

1.2-1.5 bar (18-22 psi)

Replaceable tip

Equivalent spray devices, intended for specific use with TISSEEL, may also be used. When using other spray devices, follow the instructions for use that are provided with the device. Disposal Any unused medicinal product or waste material should be disposed of in accordance with local requirements.