Tisseel Paper Insert

Fibrin Sealant VH S/D 500 IU Frozen AT /H/0317/001/IA/058/G
Package Leaflet: Information for the user
TISSEEL - Solutions for sealant
Human fibrinogen, human thrombin, synthetic aprotinin, calcium chloride dihydrate
Read all of this leaflet carefully before you start using this medicine 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 or pharmacist.
– If you get any side effects, talk to your doctor, pharmacist or nurse. This includes
any possible side effects not listed in this leaflet. See section 4.
What is in this leaflet
1. What TISSEEL is and what it is used for

2. What you need to know before you use TISSEEL
3. How to use TISSEEL
4. Possible side effects
5. How to store TISSEEL
6. Contents of the pack and other information
1. What TISSEEL is and what it is used for
What TISSEEL is
TISSEEL is a two-component tissue sealant, consisting of two solutions, the

sealer protein solution and the thrombin solution. Tisseel contains fibrinogen and
thrombin. These are two blood proteins which are important for blood
coagulation. When these proteins are mixed during application, they form a clot
at the application site.
The clot formed by TISSEEL is very similar to the clot formed in normal blood
coagulation. It is degraded in the same way as an endogenous (body’s own) clot
and does not leave any residue. A synthetic protein (synthetic aprotinin) is added,
to extend the life of the clot and to prevent premature degradation.
What TISSEEL is used for
TISSEEL is used as a supportive treatment when conventional surgical methods appear

to be insufficient:
- to improve hemostasis
- as tissue glue, to improve wound healing or to seal sutures in vascular surgery and
in the gastrointestinal tract.
- for tissue gluing, e.g. for attaching skin grafts.
TISSEEL is also effective in patients who are treated with the coagulation-inhibiting
preparation heparin.
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2. What you need to know before you use TISSEEL
Do not use TISSEEL:
- if you are allergic ( hypersensitive ) to any of the active substances or any of the
other ingredients of this medicine.
- for heavy arterial or venous bleeding. The administration of TISSEEL alone is not
indicated in this situation.
- TISSEEL must not be injected into blood vessels (veins or arteries). As TISSEEL
forms a clot at the administration site, injection into a blood vessel may result in
the formation of blood clots there. If these clots are washed into the bloodstream
they may cause life-threatening complications.
- TISSEEL is not indicated to replace skin sutures intended to close surgical
wound.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before using TISSEEL.
Take special care with TISSEEL because allergic hypersensitivity reactions may occur.
The first signs of an allergic reaction may include
- transient reddening of the skin

- itching
- hives
- nausea, vomiting
- general indisposition
- chills
- tightness of the chest
- swelling of lips and tongue
- breathing difficulties / dyspnoea
- drop in blood pressure
- increase or drop in pulse rate
When any of these symptoms occur, the application is to be discontinued without

delay. Severe symptoms require immediate emergency treatment
- because TISSEEL contains a synthetic protein known as aprotinin. Even if this

protein is applied only in small amounts and only to the wound surface, there is a
risk of severe allergic reaction. The risk appears to increase in patients who have
formerly received TISSEEL or aprotinin, even if it was well tolerated during the
previous application. Therefore any use of aprotinin or products containing
aprotinin should be recorded in your medical history. As synthetic aprotinin is
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structurally identical to bovine aprotinin the use of TISSEEL in patients with

allergies to bovine proteins should be carefully evaluated.
- because life-threatening complications through blood clots washed into the
bloodstream may result from inadvertent injection into a blood vessel.
- Intravascular application might increase the likelihood and severity of acute
hypersensitivity reactions in susceptible patients. During coronary surgery in
particular, the doctor must take special care not to inject TISSEEL into a blood
vessel. It is equally imperative that injection into the nasal mucosa is avoided,
since it may result in blood clots in the area of the ophthalmic artery.
- because there is a risk of local tissue damage in the case of injection into tissue.
- to avoid tissue sealing on undesired sites. Therefore, before administration, care
must be taken to cover all parts of the body outside the area to be treated.
- because excessive fibrin clot thickness may impact negatively on the product’s
efficacy and on wound healing. Therefore TISSEEL should only be applied as a
thin layer.
Caution must be used when applying fibrin sealant using pressurized gas.
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 CO 2 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 CO 2 should be monitored for possible occurrence of gas embolism.
When medicinal products are made from human blood or plasma, certain measures are
put in place to prevent infections from being passed on to patients. These include:
 careful selection of blood and plasma donors to make sure that those at risk of
carrying infections are excluded
 the testing of each individual donation and pools of plasma for signs of virus/
infections
 the inclusion of 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.
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The measures taken are considered effective for enveloped viruses such as human
immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, and for the non-
enveloped hepatitis A virus. 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 whose immune system is depressed
or who have some types of anemia (e.g. sickle-cell disease or hemolytic anemia).
Your doctor may recommend that you consider vaccination against hepatitis A and B if
you regularly/repeatedly receive human plasma-derived fibrin sealant.
It is strongly recommended that every time TISSEEL is administered, the name and
batch number of the medicine are documented with the enclosed self-adhesive label in
your medical history.
Other medicines and TISSEEL
Tell your doctor or pharmacist if you are taking or have recently taken any other
medicines, including medicines obtained without a prescription.
There are no known interactions with other medicinal products.
As with comparable products or thrombin solutions, the product may be destroyed by

contact with solutions containing alcohol, iodine or heavy metals (e.g. antiseptic
solutions). Care should be taken to remove such substances as much as possible before
applying the product.
See Instructions for handling and preparation for information on Oxidized cellulose-
containing preparations.
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 TISSEEL may be used during pregnancy or breast-feeding.
Driving and using machines
TISSEEL does not affect the ability to drive or operate machines.
TISSEEL contains Polysorbate 80
Polysorbate 80 may cause locally limited skin irritations such as contact dermatitis.
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3. How to use TISSEEL
The use of TISSEEL is restricted to experienced surgeons who have been trained in the
use of TISSEEL.
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).
Pressurized 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

Recommend
Spray set to be Applicator tips to be Pressure regulator ed distance Recommended
Surgery
used used to be used from target spray pressure
tissue
Tisseel / Artiss
n.a. EasySpray
Spray Set
1.5-2.0 bar
Open wound Tisseel / Artiss 10-15cm
(21.5-28.5 psi).
Spray Set 10 n.a. EasySpray
pack
Duplospray MIS
Applicator 20cm
Duplospray MIS
Applicator 30cm
Duplospray MIS
Applicator 40cm
Spray Set 360
Laparoscopic/ Endoscopic Duplospray MIS
minimally Applicator with 1.2-1.5 bar
n.a. Regulator 1.5 bar 2-5 cm
invasive Snaplock (18-22 psi)
procedures Spray Set 360
Endoscopic
Applicator with
Tether
Replaceable tip

and end tidal CO 2 should be monitored because of the possibility of occurrence of
air or gas embolism (see section 2).
The dose to be administered is always governed by your individual requirements.
The dose depends on a number of factors including the type of surgical intervention, the
size of the affected area, the mode of intended application, and the number of
applications. Your doctor will decide how much will be required and will administer
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enough to form a thin layer over the lesion. If the amount does not seem to be sufficient,
the application may be repeated.
When applying TISSEEL, clotting occurs quickly. It must be avoided to apply a new layer
to a pre-existing layer of TISSEEL, as this new layer will not adhere to an existing one.
Separate application of the Sealer Protein Component and Thrombin Component must
be avoided.
In clinical trials, individual doses of 4 to 20 ml were administered. For some procedures
(e.g. liver injuries, or the sealing of large burned surfaces), larger volumes may be
required.
As a guideline for the sealing of surfaces, 1 pack of TISSEEL 2 ml (i.e. 1 ml Tisseel

solution plus 1 ml thrombin solution) will be sufficient for an area of at least 10 cm 2.
When TISSEEL is sprayed on, the same quantity will be sufficient to coat considerably
larger areas.
It is recommended that, to avoid the formation of excess granulation tissue and to

ensure gradual degradation of the fibrin sealant, as thin a layer as possible of TISSEEL
should be applied.
To ensure adequate mixing of the sealer protein component and the thrombin
component, the first few drops of the product from the application canula should be
expelled and discarded immediately before use.
If you use more TISSEEL than you should
TISSEEL is applied only during surgical interventions. The doctor determines the
amount which will be needed. There are no known cases of overdosage.
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 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. Although they are rare, they may be severe.
The first signs of an allergic reaction may include

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- 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.
The injection of TISSEEL into blood vessels (veins or arteries) may lead to the formation
of 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:
Side effects have been evaluated on the basis of 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
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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.
General areas Side Effect Frequency

Infections and Postoperative wound infection Common
parasitic diseases
Blood and Increase of fibrin degradation products Uncommon

lymphatic system
disorders
Immune system Hypersensitivity reactions Uncommon
disorders Allergic (anaphylactic) reactions Uncommon
Anaphylactic shock Uncommon
Sensation of tingling, pricking or numbness of the skin Uncommon
Tightness of the chest Uncommon
Breathing difficulties Uncommon
Itching Uncommon
Reddening of the skin Uncommon
Nervous system Sensory disturbance Common
disorders
Cardiac disorders Increase or drop in pulse rate Uncommon
Vascular disorders Axillary venous thrombosis Common

Drop in blood pressure Rare
Bruising Uncommon
Gas bubbles in the vascular system* Not known
Blood clot in blood vessels Uncommon
Blockage of an artery in the brain Uncommon
Respiratory, and Dyspnoea Uncommon
thoracic disorders
Gastrointestinal Nausea Uncommon

disorders Intestinal obstruction Uncommon
Skin and Skin Rash Common
subcutaneous Hives Uncommon
tissue disorders Impaired healing Uncommon
Musculoskeletal Pain in extremities Common
and connective
tissue disorders
General disorders Pain Common
and administration
site conditions Increased body temperature Common
Reddening of the skin Uncommon
Swelling through the accumulation of fluid in the body Uncommon
tissue (oedema)
Pain caused by the procedure Uncommon
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Injury, poisoning Accumulation of lymph or other clear bodily fluids near Very common
and procedural the operation site (seroma)
complications
Rapid swelling of dermis, subcutaneous tissue, mucosa Uncommon
and submucosa (angioedema)
* 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 of 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 national
reporting system listed in Appendix V*>. By reporting side effects you can help provide
more information on the safety of this medicine.
5. How to store TISSEEL
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 and transport frozen (≤ -20°C) without interruption until application.
Keep the syringe in the outer carton in order to protect from light.
Storage after thawing:
The unopened product, thawed at room temperature, may be stored up to 72 hours at

controlled room temperature (not above 25°C).
After thawing, the solution must not be re-frozen or refrigerated!
Do not throw away any medicines via wastewater or household waste. Ask your
pharmacist how to throw away medicines you no longer use. These measures will help
protect the environment.
6. 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;
synthetic aprotinin, 3000 KIU/ml.
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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 in 1 ml thrombin solution are: human thrombin, 500 IU/ml; calcium
chloride dihydrate, 40 μmol/ml.
The other ingredients are: human albumin, sodium chloride, Water for Injections.
After mixing 1 ml 2 ml 4 ml 10 ml
Component 1: Sealer
protein solution
Human fibrinogen (as 45.5 mg 91mg 182 mg 455 mg

clottable protein)
Synthetic aprotinin 1500 KIU 3000 KIU 6000 KIU 15000 KIU
Component 2: Thrombin
solution
Human thrombin 250 IU 500 IU 1000 IU 2500 IU

Calcium chloride 20 μmol 40 μmol 80 μmol 200 μmol
dihydrate
TISSEEL contains 0.6 – 5 IU/ml human factor XIII which is isolated from the plasma
together with human fibrinogen.
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What TISSEEL looks like and contents of the pack
Solutions for sealant.

The sealer protein solution and the thrombin solution are supplied in a plastic syringe for
single use.
The frozen solutions are colorless to pale yellow, opalescent;
After thawing, they are colorless to pale yellow.
TISSEEL is provided in the following final container:
<Content of package with PRIMA Syringe:

1 ml, 2 ml or 5 ml sealer protein solution and 1 ml, 2 ml or 5 ml thrombin solution in a
pre-filled double chamber syringe (polypropylene) closed with a tip cap packed in two
bags and with a device with 2 joining pieces and 4 applications cannulas.>
<Content of package with AST Syringe:

1 ml, 2 ml or 5 ml sealer protein solution and 1 ml, 2 ml or 5 ml thrombin solution in a
pre-filled double chamber syringe (polypropylene) closed with a tip cap packed in two a
bags and with a device with 2 joining pieces, 4 applications cannulas and one double
piston plunger.>
Pack sizes:
TISSEEL 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).
The solutions are frozen.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder: [To be completed nationally]
<Manufacturer: Baxter AG, Industriestrasse 67, A-1221 Vienna, Austria>
<Manufacturer: Takeda Manufacturing Austria AG, Industriestrasse 67, 1221 Vienna,

Austria>
This medicinal product is authorised in the Member States of the EEA under the
following names:
Austria: TISSEEL - Lösungen für einen Gewebekleber

Bulgaria: TИСИЛ - разтвори за тъканно лепило
Czech Republic: TISSEEL - roztoky pro lepidlo
France: TISSEEL - solutions pour colle
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Germany: TISSEEL 2 ml
TISSEEL 4 ml
TISSEEL 10 ml
Greece: TISSEEL - Διαλύματα για στεγανοποιητικό
Malta: TISSEEL - Solutions for sealant
Norway: TISSEEL
Poland: TISSEEL - klej tkankowy
Slovak Republic: TISSEEL - fibrínové lepidlo
Spain: TISSEEL - soluciones para adhesivo tisular
This leaflet was last revised in {MM/YYYY}.
< The following information is intended for medical or healthcare professionals only (final
container: PRIMA Syringe):
General
 Before the administration of TISSEEL, cover all parts of the body outside the
area to be treated in order to prevent tissue adhesion at undesired sites.
 To prevent TISSEEL from adhering to surgical gloves and instruments, wet these
with sodium chloride solution before contact.
 The guideline for sealing surfaces is: One package of Tisseel 2 ml (i.e. 1 ml
sealer protein solution plus 1 ml thrombin solution) is sufficient for a surface of at
least 10 cm 2.
 The dose required depends on the size of the surface to be sealed.
 Do NOT apply the two components of TISSEEL separately. Both components

must be applied together.
 Do NOT expose TISSEEL to temperatures above 37°C. Do NOT microwave.

 Do NOT thaw the product by holding it in your hands.
 Do NOT use TISSEEL 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. 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

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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.
Table 1 – PRIMA Syringe: Minimum thawing and warming times using a sterile
water bath
Minimum Thawing/Warming Times

Pack Size 33°C to 37°C, Sterile Water Bath
Product without bags
2 ml 5 minutes
4 ml 5 minutes
10 ml 10 minutes
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 2). 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 and the plunger into the sterile area.
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Table 2 – PRIMA Syringe: Minimum thawing and warming times using a non-sterile
water bath

33°C to 37°C, Non-sterile Water
Pack Size
Bath
Product in bags
2 ml 15 minutes
4 ml 20 minutes
10 ml 35 minutes
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 3). 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.
Table 3 – PRIMA Syringe: Minimum thawing and warming times in an incubator
Minimum Thawing /Warming Times

Pack Size 33°C to 37°C, Incubator
Product in bags
2 ml 40 minutes
4 ml 50 minutes
10 ml 90 minutes
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 4). Once
thawed, in order to warm the product for use, warm it in the outer bag in an
incubator.
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Table 4 – PRIMA Syringe: Minimum thawing times at room temperature outside of

the sterile field and additional warming times in an incubator to 33°C to 37°C
Warming times prior to use

Minimum thawing times of
to 33°C to a maximum of
product at room temperature
Pack Size 37°C in the incubator after
(not above 25°C)
thawing at RT
product in bags
product in bags
2 ml 80 minutes + 11 minutes
After thawing at room temperature, the product 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 on any account.
 Remove the syringe from the bags shortly before use.

 Use TISSEEL only when it is thawed and warmed completely (liquid
consistency).
 Remove the protective cap from the syringe immediately before application.
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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
Tether Strap
Double Plunger
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 nozzles of the dual chamber ready-to-use syringe to the joining piece
ensuring that they are firmly attached.
o Secure the joining piece by fastening the tether strap to the double
chamber ready-to-use syringe.
o If the tether strap tears, use the spare joining piece provided in the kit.
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.
 Attach an application cannula on to the joining piece.
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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
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 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, only 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.
Oxidized cellulose-containing preparations should not be used with TISSEEL
because the low pH interferes with the activity of the thrombin
In certain applications, biocompatible material, such as collagen fleece, is used

as a carrier substance or for reinforcement.
Spray Application
When applying TISSEEL using a spray device be sure to use a pressure and a distance
from tissue within the ranges recommended by the manufacturer as follows:

Recommend
Surgery
tissue
Tisseel / Artiss 1.5-2.0 bar
Open wound n.a. EasySpray 10-15cm
Spray Set (21.5-28.5 psi).
Oct 2018
17/26
Tisseel / Artiss
pack
Duplospray MIS
Applicator 20cm
Duplospray MIS
Applicator 30cm
Duplospray MIS
Applicator 40cm
Laparoscopic/
Spray Set 360 Duplospray MIS
minimally 1.2-1.5 bar
n.a. Endoscopic Regulator 1.5 bar 2-5 cm
invasive (18-22 psi)
Applicator with
procedures
Snaplock
Spray Set 360
Endoscopic
Applicator with
Tether
Replaceable tip

For the application of TISSEEL 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.>
Oct 2018
18/26
< The following information is intended for medical or healthcare professionals only (final
container: AST Syringe):
General
 Before the administration of TISSEEL, cover all parts of the body outside the
area to be treated in order to prevent tissue adhesion at undesired sites.
 To prevent TISSEEL from adhering to surgical gloves and instruments, wet these
with sodium chloride solution before contact.
 The guideline for sealing surfaces is: One package of Tisseel 2 ml (i.e. 1 ml
sealer protein solution plus 1 ml thrombin solution) is sufficient for a surface of at
least 10 cm 2.
 The dose required depends on the size of the surface to be sealed.
 Do NOT apply the two components of TISSEEL separately. Both components

must be applied together.
 Do NOT expose TISSEEL to temperatures above 37°C. Do NOT microwave.

 Do NOT thaw the product by holding it in your hands.
 Do NOT use TISSEEL 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.
 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
Oct 2018
19/26
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.
Table 1 – AST Syringe: Minimum thawing and warming times using a sterile water
bath

Pack Size 33°C to 37°C, Sterile Water Bath
Product without bags
2 ml 5 minutes
4 ml 5 minutes
10 ml 12 minutes
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 2). 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 and the plunger into the sterile area.
Table 2 – AST Syringe: Minimum thawing and warming times using a non-sterile
water bath

33°C to 37°C, Non-sterile Water
Pack Size
Bath
Product in bags
2 ml 30 minutes
4 ml 40 minutes
10 ml 80 minutes
Oct 2018
20/26
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 3). 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.
Table 3 – AST Syringe: Minimum thawing and warming times in an incubator
Minimum Thawing /Warming

Times
Pack Size
33°C to 37°C, Incubator
Product in bags
2 ml 40 minutes
4 ml 85 minutes
10 ml 105 minutes
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 4). Once
thawed, in order to warm the product for use, warm it in the outer bag in an
incubator.
Table 4 – AST Syringe: Minimum thawing times at room temperature outside of the
sterile field and additional warming times in an incubator to 33°C to 37°C
Minimum thawing times of Warming times prior to use

product at room to 33°C to a maximum of
Pack Size temperature (not above 37°C in the incubator after
25°C) thawing at RT
product in bags product in bags
After thawing at room temperature, the product 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.
Oct 2018
21/26
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 on any account.
 Remove the syringe from the bags shortly before use.

 Use TISSEEL only when it is thawed and warmed completely (liquid
consistency).
 Remove the protective cap from the syringe immediately before application.
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.
Oct 2018
22/26
Operating instructions for AST Syringe
Tether Strap Double Plunger
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 nozzles of the dual chamber ready-to-use syringe to the joining piece
ensuring that they are firmly attached.
o Secure the joining piece by fastening the tether strap to the double
chamber ready-to-use syringe.
o If the tether strap tears, use the spare joining piece provided in the kit.
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.
 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
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.
Oct 2018
23/26
 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 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, only 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.
Oxidized cellulose-containing preparations should not be used with TISSEEL

because the low pH interferes with the activity of the thrombin.
In certain applications, biocompatible material, such as collagen fleece, is used

as a carrier substance or for reinforcement.
Oct 2018
24/26
Spray Application
When applying TISSEEL using a spray device be sure to use a pressure and a distance
from tissue within the ranges recommended by the manufacturer as follows:

Recommend
Surgery
tissue
Tisseel / Artiss
n.a. EasySpray
Spray Set
1.5-2.0 bar
Open wound Tisseel / Artiss 10-15cm
(21.5-28.5 psi).
pack
Duplospray MIS
Applicator 20cm
Duplospray MIS
Applicator 30cm
Duplospray MIS
Applicator 40cm
Laparoscopic/
Spray Set 360 Duplospray MIS
minimally 1.2-1.5 bar
n.a. Endoscopic Regulator 1.5 bar 2-5 cm
invasive (18-22 psi)
Applicator with
procedures
Snaplock
Spray Set 360
Endoscopic
Applicator with
Tether
Replaceable tip

For the application of TISSEEL 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.>
Oct 2018
25/26
Oct 2018
26/26

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Fibrin Sealant VH S/D 500 IU Frozen AT /H/0317/001/IA/058/G

Package Leaflet: Information for the user

TISSEEL - Solutions for sealant

Human fibrinogen, human thrombin, synthetic aprotinin, calcium chloride dihydrate

What is in this leaflet

1. What TISSEEL is and what it is used for

1. What TISSEEL is and what it is used for

TISSEEL is a two-component tissue sealant, consisting of two solutions, the

What TISSEEL is used for

TISSEEL is used as a supportive treatment when conventional surgical methods appear

2. What you need to know before you use TISSEEL

Do not use TISSEEL:

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using TISSEEL.

The first signs of an allergic reaction may include

- transient reddening of the skin

When any of these symptoms occur, the application is to be discontinued without

- because TISSEEL contains a synthetic protein known as aprotinin. Even if this

structurally identical to bovine aprotinin the use of TISSEEL in patients with

TISSEEL should be administered strictly according to the instructions and only

When spraying TISSEEL, changes in blood pressure, pulse, oxygen saturation

Other medicines and TISSEEL

There are no known interactions with other medicinal products.

As with comparable products or thrombin solutions, the product may be destroyed by

TISSEEL with food and drink

Pregnancy, breast-feeding and fertility

Driving and using machines

TISSEEL does not affect the ability to drive or operate machines.

TISSEEL contains Polysorbate 80

3. How to use TISSEEL

Recommended pressure, distance and devices for spray application of TISSEEL

When spraying TISSEEL, changes in blood pressure, pulse, oxygen saturation

The dose to be administered is always governed by your individual requirements.

As a guideline for the sealing of surfaces, 1 pack of TISSEEL 2 ml (i.e. 1 ml Tisseel

It is recommended that, to avoid the formation of excess granulation tissue and to

If you use more TISSEEL than you should

4. Possible side effects

The first signs of an allergic reaction may include

- transient reddening of the skin (“flushing”)

In isolated cases, these reactions may progress to severe allergic reactions

Even if repeated treatment with TISSEEL was well tolerated, a subsequent

Very common: may affect more than 1 in 10 people

Rare: may affect up to 1 in 1,000 people

General areas Side Effect Frequency

Blood and Increase of fibrin degradation products Uncommon

Vascular disorders Axillary venous thrombosis Common

Gastrointestinal Nausea Uncommon

Reporting of side effects

5. How to store TISSEEL

Keep this medicine out of the sight and reach of children.

Store and transport frozen (≤ -20°C) without interruption until application.

Storage after thawing:

The unopened product, thawed at room temperature, may be stored up to 72 hours at

After thawing, the solution must not be re-frozen or refrigerated!

6. Contents of the pack and other information

What TISSEEL contains

TISSEEL consists of two components:

Component 1: Sealer protein solution

The other ingredients are: human albumin, L-histidine, niacinamide, polysorbate 80