solutions for tissue
glue Human fibrinogen, human thrombin, human factor XIII, synthetic aprotinin, calcium chloride dihydrate
What Tisseel is and what it is used for
Tisseel is a tissue glue that contains fibrinogen and thrombin. Two blood proteins are important for the blood to coagulate (solidify).
Tisseel is used as a supportive treatment when the normal surgical technique is not enough:
- to help stop bleeding
- as a tissue adhesive to seal wounds or to seal surgical sutures in surgical procedures, including procedures in the blood vessels, gastrointestinal tract, nervous system, and procedures where contact with cerebrospinal fluid or hard brain membrane (dura mater) may occur (e.g. ear-nose- neck, eye, and spinal cord surgery)
- as a tissue adhesive, e.g. when adhering to skin graftsTisseel also affects patients treated with the drug heparin, which prevents coagulation.
What you need to know before using Tisseel
Do not use Tisseel
If you are allergic to any of the active substances or any other ingredient in this medicine (listed in section 6).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Tisseel:
- If you have previously been treated with Tisseel or aprotinin. Tisseel contains a synthetic protein, aprotinin. Even if this is only applied directly to the wound surface, there is a risk of severe allergic reactions. The risk appears to be increased in patients previously treated with Tisseel or aprotinin, even if it was well tolerated during the previous treatment session. Therefore, treatment with aprotinin or products containing aprotinin should be noted in your medical record.
Life-threatening/fatal air or gas embolism (air entering the bloodstream, which can be serious or life-threatening) has occurred very rarely when pressure regulator spray sets are used to administer fibrin tissue glue. This appears to be related to using the spray set at higher pressures than recommended and/or close to the tissue surface. The risk appears to be greater when fibrin tissue glue is sprayed with air compared to CO 2 and therefore cannot be excluded when Tisseel is sprayed in open surgery.
The spray set and associated tips have instructions for use with recommendations for pressure intervals and spraying distance from the tissue surface.
Tisseel should only be administered in strict accordance with the instructions and only in conjunction with the devices recommended for this product.
When Tisseel is sprayed on, changes in blood pressure, pulse, oxygen saturation and end-tidal CO 2 should be monitored for possible gas embolism.
Tisseel contains human fibrinogen, factor XIII, and thrombin, which are made from human plasma. When medicines are made from human plasma or blood, special measures are taken to prevent infection from being passed on to patients. This includes:
- careful selection of blood and plasma donors to ensure that people at risk of being carriers are excluded
- testing of individual donations and plasma pools for signs of virus/infection.
- The manufacturers of these products also include steps in the processing of blood and plasma that can inactivate and separate viruses.
Despite these measures, the risk of transmission of infection cannot be completely excluded when medicinal products made from human blood or plasma are given. This also applies to new, hitherto unknown viruses and other types of infection.
The measures taken are considered effective against enveloped viruses, such as human immunodeficiency virus ( HIV ), hepatitis B virus: and hepatitis C virus, and the non-enveloped hepatitis A virus et.
The measures may be of limited value against non-enveloped viruses such as parvovirus B19.
Parvovirus B19 infection can be severe for pregnant women ( infection of the fetus), individuals with weakened immune systems, or patients with certain types of anemia (eg, hemolytic anemia ).
When you are given Tisseel, it is strongly recommended that the product name and batch number be recorded to enable tracking of the product used.
Tisseel should not be given in a blood vessel or in tissue that contains many blood vessels, such as e.g. the nasal mucosa, due to the risk of blood clots and allergic reactions.
Children and young people
Safety and effectiveness for children have not been established.
Other medicines and Tisseel
Tell your doctor or pharmacist if you are using, have recently used, or might be using other medicines.
There are no known interactions with other drugs.
Pregnancy, breastfeeding, and fertility
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
The effects of Tisseel on fertility have not been established.
Driving ability and use of machinery
Information on whether Tisseel affects the ability to drive and use machines is not relevant, as Tisseel is only given in connection with hospital care.
Tisseel contains human albumin, L-histidine, niacinamide, polysorbate 80, sodium citrate dihydrate, sodium chloride, and water for injections
How to use Tisseel
The use of Tisseel is restricted to experienced surgeons who have received training in the use of Tisseel.
Before Tisseel is applied, the surface area of the wound must be dried using standard techniques (eg, repeated application of compresses or cotton swabs, or using suction devices). Do not use compressed air or compressed gas to dry the area.
When applying Tisseel using a spray set, be sure to use pressure and distance from tissue one that is within the range recommended by the manufacturer as follows:
| Recommended pressure, distance, and device for spraying Tisseel | |||||
| Type of intervention | Spray set to be used | Applicator tips to be used | Pressure regulator to be used | Recommended distance from target tissue one | Recommended spray pressure |
| Open procedures | Tisseel/Artiss spray set | not applicable | EasySpray | 10‑15 cm | 1.5‑2.0 bar (21.5‑28.5 psi). |
| Tisseel/Artiss spray set 10 pack | not applicable | EasySpray | |||
| Laparoscopic/minimally invasive procedures | not applicable | Duplo-spray MIS applicator20 cm | Duplospray MIS regulator | 2-5 cm | 1.2–1.5 bar (18–22 psi) |
| Duplospray MIS regulator NIST B11 | |||||
| Duplo-spray MIS applicator30 cm | Duplospray MIS regulator | ||||
| Duplospray MIS regulator NIST B11 | |||||
| Duplo-spray MIS applicator40 cm | Duplospray MIS regulator | ||||
| Duplospray MIS regulator NIST B11 | |||||
| Interchangeable tip | Duplospray MIS regulator | ||||
| Duplospray MIS regulator NIST B11 |
When Tisseel is sprayed on, changes in blood pressure, pulse, oxygen saturation and end-tidal CO 2 should be monitored for the risk of air or gas embolism (see section 2).
The dose of Tisseel used depends on several factors such as, example, the type of operation, the size of the area to be treated during the operation, the way Tisseel is applied, and the number of applications. Your doctor will decide how much is appropriate and will apply enough to form a thin layer over the wound. If the amount does not seem to be sufficient, the application may need to be repeated.
If you used too much Tisseel
Tisseel is only applied during a surgical procedure. The amount used is determined by the surgeon. There are no known cases of overdose.
If you have further questions about this medicine, contact your doctor or pharmacist.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
In patients treated with this type of medicine, hypersensitivity reactions or allergic reactions may occur. They are rare but can be serious.
Signs of an allergic reaction may include:
- Hot flashes
- Rashes, including hives
- Nausea, vomiting
- Headache
- Dormancy
- Restlessness
- Burning and stinging sensation at the application site
- Burning
- Overindulge
- Pressure over the chest
- Swelling of the lips, tongue, and throat (which may result in difficulty breathing and/or swallowing)
- Difficulty breathing
- Low blood pressure
- Increased pulse rate
- Unconsciousness due to a drop in blood pressure
In some cases, these reactions can develop into severe allergic reactions ( anaphylaxis ). This applies especially if the medicine is applied several times, or is used on patients who have previously shown hypersensitivity to aprotinin or other ingredients in Tisseel.
Although repeated treatment with Tisseel has been well tolerated, a further application of Tisseel or an infusion of aprotinin may result in severe allergic (anaphylactic) reactions.
The responsible surgical team is well aware of the risk of this type of reaction and will immediately discontinue the application of Tisseel at signs of hypersensitivity. Severe symptoms may require emergency care.
If Tisseel is applied to soft tissue, it may cause local tissue damage.
If Tisseel is applied to blood vessels, it can lead to blood clots forming ( thrombosis ) or an anaphylactic reaction occurring.
Antibodies against ingredients in Tisseel may occur in rare cases.
The following side effects have also been observed during treatment with Tisseel:
Uncommon (may affect more than 1 in 1,000 users)
- The increased amount of breakdown products from fibrin in the blood
- Nausea
- Pain in connection with the procedure
Rare (may affect more than 1 in 10,000 users ) - Low blood pressure
Has been reported (occurring in an unknown number of users)
- Allergic (anaphylactic/anaphylactoid) reactions, hypersensitivity reaction etc.
- Stinging sensation in the skin
- Increase or decrease in pulse rate
- Blood clot
- Air bubbles in the blood vessels (air embolism)
- Difficulty breathing, shortness of breath, spasm of the airways ( bronchospasm )
- Itching, hives, redness of the skin
- Heatwave
- Swelling of the skin
- Impaired healing
How to store Tisseel
Keep this medicine out of the sight and reach of children.
Use before the expiry date stated on the carton and label after Ex. dat. or EXP. The expiration date is the last day of the specified month.
Store in a deep-frozen state (-20°C or colder). The frying chain must not be broken before use.
Store the syringes in the outer carton. Light sensitive.
Storage after thawing:
The thawed solution can be used for up to 72 hours if stored in unopened, undamaged, sterile packaging at no more than 25°C.
The thawed and warmed solution can be used for up to 12 hours if stored in unopened, undamaged, sterile packaging at no more than 37°C.
If Tisseel is not used within the above time intervals after thawing, the solutions must be discarded.
Once Tisseel has been taken out of the freezer, it must not be re-frozen or stored cold!
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
Tisseel contains two components:
Component 1 (protein solution)
The active substances in 1 ml are:
Human fibrinogen (coagulable protein ) 91 mg, synthetic aprotinin 3000 KIE, human factor XIII0.6 – 10 IU.
Excipients are human albumin, L-histidine, niacinamide, polysorbate 80, sodium citrate dihydrate, and water for injections.
Component 2 (thrombin solution)
The active substances in 1 ml are:
Human thrombin 500 IU, calcium chloride dihydrate 40 µmol.
Excipients are human albumin, sodium chloride, and water for injections.
Appearance and package sizes of the medicine
The appearance of the drug:
Colorless to pale yellow and clear to slightly opaque solutions.
Package contents:
Component 1 and Component 2 are supplied in a ready-to-use pre-filled syringe (Prima syringe ) for single use.
Tisseel is supplied in the following packaging:
PRIMA syringe, a double-chamber polypropylene syringe closed with a protective cap on the mouth, for single use.
Contents of the package with PRIMA syringe:
- A pre-filled syringe with two containers (made of polypropylene) contains 1 ml, 2 ml, or 5 ml of component 1 and respectively 1 ml, 2 ml, or 5 ml of component 2. The syringe tip is fitted with a protective cap.
- The syringe is packed in two bags and comes with 2 main nozzles and 4 application needles as accessories.
Package sizes
Tisseel is supplied in the following pack sizes: 1 or 10 x 2 ml (1 ml + 1 ml), 1 or 10 x 4 ml (2 ml + 2 ml) and 1 or 10 x 10 ml (5 ml + 5 ml).
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Baxter Medical AB
Box 63
164 94 Coffin
Manufacturer
Baxter AG
Industriestraße 67
1220 Vienna
Austria