Veraseal

Package leaflet: Information for the user

VeraSeal fibrin sealant

human fibrinogen/human thrombin
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor. See section 4. Contents of this leaflet
  1. What VeraSeal is and what it is used for
  2. What you need to know before being treated with VeraSeal
  3. How VeraSeal is used
  4. Possible side effects
  5. How to store VeraSeal
  6. Contents of the pack and other information

1. What VeraSeal is and what it is used for

VeraSeal contains human fibrinogen and human thrombin, two proteins derived from blood, which form a clot when mixed.
VeraSeal is used as a tissue adhesive during surgical procedures in patients. It is applied to the surface of bleeding tissue to reduce bleeding during and after surgery when standard surgical techniques are not sufficient.
VeraSeal is indicated in all age groups.

2. What you need to know before being treated with VeraSeal

Your surgeon must not treat you with VeraSeal:

• if you are allergic to human fibrinogen or human thrombin or to any of the other components of this medicine (listed in section 6). VeraSeal must not be applied inside blood vessels. VeraSeal must not be used to treat severe or rapid bleeding from an artery.

Warnings and precautions

Allergic reactions may occur. Signs of such reactions include hives, rash, chest tightness, wheezing, low blood pressure (e.g. dizziness, fainting, blurred vision) and anaphylaxis (a serious, rapidly developing reaction). If these symptoms occur during surgery, use of the medicine must be stopped immediately.

The spray application of VeraSeal should only be performed if the spraying distance can be accurately assessed. The spray device must not be used at a distance closer than recommended.

Special safety warning

For medicines such as VeraSeal that are derived from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These include careful selection of blood and plasma donors to ensure exclusion of donors at risk of carrying infections, and testing of each donation and plasma pool to detect signs of viruses/infections. Manufacturers also employ processes during blood or plasma treatment that can inactivate or eliminate viruses. Despite these measures, when administering medicines prepared from human blood or plasma, the possibility of transmitting an infection cannot be completely ruled out. This also applies to any unknown or emerging viruses or other types of infections. The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and against the non-enveloped hepatitis A virus. However, these measures may have limited effectiveness against non-enveloped viruses such as parvovirus B19. Infection with parvovirus B19 may be serious in pregnant women (fetal infection) and in individuals with a weakened immune system or suffering from certain types of anaemia (e.g. sickle cell anaemia or haemolytic anaemia).

It is strongly recommended that each time you are treated with VeraSeal, a healthcare professional records the name and batch number of the medicine to maintain documentation of the batches used.

Children and adolescents

The use of VeraSeal is recommended in children and adolescents under 18 years of age.

Other medicines and VeraSeal

The product may be affected following contact with solutions containing alcohol, iodine, or heavy metals (such as antiseptic solutions).

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Pregnancy and breastfeeding

If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding, consult your doctor before being treated with this medicine. Your doctor will decide whether you should be treated with this medicine.

3. How VeraSeal is used

The use of VeraSeal is restricted to experienced surgeons who have been trained in the use of this
medicinal product.
The surgeon will apply VeraSeal to the surface of blood vessels or to the surface of internal organ tissues, using an application device during the surgical procedure. This device enables simultaneous administration of equal amounts of the two components of VeraSeal and ensures their uniform mixing, which is important for optimal tissue adhesive performance.
The amount of VeraSeal to be applied depends on several factors, including the type of surgical procedure, the size of the area to be treated during surgery, and the method of application. The surgeon will determine the appropriate dose and will apply a sufficient quantity to form a thin, uniform layer. If this appears insufficient, a second layer may be applied.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
VeraSeal contains the fibrin-based tissue adhesive component. Fibrin-based tissue adhesives may in rare cases (up to 1 in 1,000 people) cause an allergic reaction. If an allergic reaction occurs, one or more of the following symptoms may appear: swelling under the skin (angioedema), skin rash, hives or wheals (urticaria), chest tightness, chills, flushing, headache, low blood pressure, lethargy, nausea, restlessness, increased heart rate, tingling, vomiting or wheezing. In isolated cases, these reactions may progress to a severe allergic reaction. Allergic reactions may be particularly observed if the product is applied repeatedly or administered to patients with known hypersensitivity to the components of the product. If you experience any of these symptoms after surgery, consult your doctor or surgeon immediately.
There is also a theoretical possibility that the immune system may produce proteins that react against VeraSeal, and these may interfere with blood clotting. The frequency of such events is unknown.
If the product is accidentally introduced into a blood vessel, it may cause blood clots, including disseminated intravascular coagulation (in which blood clots form throughout the body's blood vessels). There is also a risk of a severe allergic reaction.

The side effects reported during clinical trials conducted with VeraSeal included:

More serious side effects
Uncommon (may affect up to 1 in 100 people):

• Abdominal abscess (in the abdomen) (swelling in an area of the abdomen caused by infection)
• Dehiscence of abdominal wound (in the abdomen) due to incomplete healing
• Bile leakage (a fluid produced by the liver) after surgery
• Cellulitis (skin infection)
• Deep vein thrombosis (blood clots in blood vessels)
• Hepatic abscess (swelling in an area of the liver caused by infection)
• Peritonitis (inflammation of the abdominal wall)
• Positive test for Parvovirus B19 (laboratory result indicating infection with this virus)
• Post-operative wound infection
• Pulmonary embolism (blood clot in the blood vessels of the lungs)
• Wound infection

Other side effects
Common (may affect up to 1 in 10 people):

• Nausea
• Pain caused by surgery
• Itching

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

• Anaemia (insufficient number of red blood cells)
• Anxiety
• Atrial fibrillation (irregular heartbeat)
• Back pain
• Bladder spasm
• Chills
• Conjunctival irritation (eye irritation)
• Constipation
• Contusion (bruising)
• Reduced urine output
• Difficulty breathing
• Pain or difficulty urinating
• Bruising
• Erythema (redness of the skin)
• Flatulence (intestinal gas)
• Headache
• Elevated body temperature
• Low or high blood pressure
• High or low levels of white blood cells in the blood
• High levels of potassium in the blood
• Ileus (intestinal obstruction)
• Altered blood coagulation
• Erythema at incision site (redness of the skin at the incision site)
• Infection at incision site
• Increased bilirubin levels in the blood
• Increased liver enzyme levels
• Increased or decreased glucose levels in the blood
• Insomnia
• Low blood pressure due to surgery
• Low calcium levels in the blood
• Low magnesium levels in the blood
• Low oxygen levels in the blood
• Low potassium levels in the blood
• Low protein levels in the blood
• Low red blood cell levels due to blood loss
• Low sodium levels in the blood
• Peripheral oedema (fluid accumulation)
• Pain, not specified
• Pain at incision site
• Limb pain
• Plasmacytoma (tumour of blood cells)
• Pleural effusion (abnormal amount of fluid around the lungs)
• Pleuritis (inflammation of the lung walls)
• Post-procedural haemorrhage (bleeding after procedure)
• Post-procedural infection (infection after procedure)
• Pulmonary oedema (excess watery fluid in the lungs)
• Retroperitoneal haematoma (collection of blood in the abdomen)
• Rales (rattling sounds in the lungs)
• Somnolence
• Urinary retention
• Vascular graft complication (complication of vascular bypass)
• Thrombosis of vascular graft (blood clots in the vascular bypass)
• Ventricular tachycardia (rapid heartbeats)
• Bruising at blood vessel puncture site
• Vomiting
• Wheezing
• Wound discharge

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or surgeon. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How VeraSeal is stored

VeraSeal must be kept out of the sight and reach of children.
This medicinal product must not be used after the expiry date stated on the
syringe label and on the blister label after “EXP” and on the carton after “Scad”.
It must be stored and transported frozen (-18 °C or lower). The cold chain
must not be broken until the time of use. Keep the sterilized blister in the
outer packaging to protect the medicinal product from light. Thaw completely before use.
Do not refreeze once thawed. After thawing, it can be stored for up to
7 days at a temperature between 2 °C and 8 °C or for 24 hours at a temperature not exceeding 25 °C prior to use.
Once the blister is opened, VeraSeal must be used immediately.
Do not use if the solutions appear cloudy or contain particulate matter.
Dispose of the product if the packaging is damaged.

6. Package contents and other information

What VeraSeal contains
The active substances are:

• Component 1: human fibrinogen
• Component 2: human thrombin

The other components are:

• Component 1: disodium citrate dihydrate, sodium chloride, arginine, isoleucine, monosodium glutamate, water for injections.
• Component 2: calcium chloride, human albumin, sodium chloride, glycine, water for injections.

Description of the appearance of VeraSeal and package contents
VeraSeal is presented as solutions for tissue adhesive. It is supplied as a single-use kit containing two pre-filled syringes assembled in a syringe holder. Frozen solutions. After thawing, the solutions are clear or slightly opalescent and colourless or pale yellow. The product is supplied with a double applicator and two additional airless spray tips, for spray or dropwise application. The airless spray tips are radiopaque. See the following figure.

VeraSeal is available in the following pack sizes:

• VeraSeal 2 mL (containing 1 mL of human fibrinogen and 1 mL of human thrombin)
• VeraSeal 4 mL (containing 2 mL of human fibrinogen and 2 mL of human thrombin)
• VeraSeal 6 mL (containing 3 mL of human fibrinogen and 3 mL of human thrombin)
• VeraSeal 10 mL (containing 5 mL of human fibrinogen and 5 mL of human thrombin)

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Instituto Grifols, S.A.
Can Guasc, 2 - Parets del Vallès
E - 08150 Barcelona - Spain

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

AT/BE/BG/CY/EE/EL/HR/HU/IE/LV/CZ/LT/LU/MT/NL/RO/SI/SK/UK(NI)
Grifols S.R.O.
Instituto Grifols, S.A.
Tel: +4202 2223 1415
Tel: +34 93 571 01 00

DE/DK/FI/IS/NO/SE
Grifols Deutschland GmbH
Grifols Nordic AB
Tel: +49 69 660 593 100
Tel: +46 8 441 89 50

ES/FR
Johnson & Johnson, S.A.
Johnson & Johnson Medical S.A.S.
Tel: +34 91 722 80 00
Tél: +33 (0)1 55 00 22 33

IT/PL
Grifols Italia S.p.A.
Grifols Polska Sp. z o.o.
Tel: +39 050 8755 113
Tel: +48 22 378 85 60

PT
Grifols Portugal, Lda.
Tel: +351 219 255 200

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

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The following information is intended exclusively for healthcare professionals:

Dosage and method of administration
The use of VeraSeal is restricted to experienced surgeons who have been trained in the use of this
medicinal product.
The amount of VeraSeal to be applied and the frequency of application must always be determined according to the patient's underlying clinical needs.
The dose to be applied depends on several variables, including the type of surgical procedure, the size of the area, the intended mode of application, and the number of applications.
Application of the product must be individualized by the physician. In clinical trials, individual doses generally ranged from 0.3 to 12 mL. Larger quantities may be required for other procedures.
The initial amount of product applied to the selected anatomical site or surface to be treated should be sufficient to completely cover the intended area of application. VeraSeal must be applied in a thin layer. Application may be repeated if necessary.

Incompatibilities
This medicinal product must not be mixed with other medicinal products.

Special precautions
For topical use only. Do not administer intravascularly.
If the product is accidentally administered intravascularly, potentially life-threatening thromboembolic complications may occur.
When using accessory tips, the corresponding instructions must be followed.
Prior to administration of VeraSeal, care must be taken to adequately protect (cover) body areas outside the intended application site to prevent tissue adhesion at unintended sites.
VeraSeal must be applied in a thin layer. Excessive clot thickness may negatively interfere with the effectiveness of the product and with the wound healing process.

Instructions for use
Read this leaflet before opening the package. See the pictograms at the end of this leaflet.

Handling of VeraSeal
VeraSeal is supplied ready for use in sterilized packaging and must be handled using sterile techniques under aseptic conditions. Discard damaged packages, as re-sterilization is not possible.
A summary of thawing methods and storage after thawing is provided in Table 1.

Table 1. Thawing and storage after thawing

• Preferred thawing methods Refrigerator thawing
  1. Remove the box from the freezer and place it in the refrigerator for thawing at a temperature between 2 °C and 8 °C for a minimum of 7 hours for 2 mL and 4 mL packs, and a minimum of 10 hours for 6 mL and 10 mL packs. After thawing, there is no need to warm the product before use. After thawing, solutions should appear clear to slightly opalescent and colourless to light yellow. Solutions that appear cloudy or contain particulate matter must not be used.

Thawing at a temperature between 20 °C and 25 °C
Remove the box from the freezer, open it and remove the two blisters. Leave the blister containing the double applicator at room temperature between 20 °C and 25 °C until the fibrin-based tissue adhesive is ready for use. Thaw the blister with pre-filled syringes of VeraSeal at a temperature between 20 °C and 25 °C by following the procedure below:

1. Place the blister containing the syringe holder with pre-filled syringes on a surface at a temperature between 20 °C and 25 °C for a minimum of 70 minutes for 2 mL and 4 mL packs, and a minimum of 90 minutes for 6 mL and 10 mL packs. After thawing, there is no need to warm the product before use.

After thawing, the solutions should appear clear to slightly opalescent and colourless to light yellow. Solutions that appear cloudy or contain particulate matter must not be used.

Storage after thawing
After thawing, the kit containing the syringe holder with pre-filled syringes and the double applicator of VeraSeal may be stored for up to 7 days in a refrigerator at 2 °C to 8 °C, or for 24 hours at a temperature not exceeding 25 °C prior to use, provided it remains sealed in the original packaging. Once the blisters are opened, use VeraSeal immediately and discard any unused contents.
Do not refreeze once thawed.

Instructions for transfer

1. After thawing, remove the blister from the surface at 20 °C to 25 °C, or from the refrigerator at 2 °C to 8 °C.
2. Open the blister and ensure that the pre-filled syringes of VeraSeal are completely thawed. Make the syringe holder with pre-filled syringes of VeraSeal available to a second person for transfer to the sterile field. The exterior of the blister must not come into contact with the sterile field. See Figure 1.

• Sterile water bath (rapid thawing) *

Remove the box from the freezer, open it and remove the two blisters.
Leave the blister containing the double applicator at room temperature between 20 °C and 25 °C until the fibrin-based tissue adhesive is ready for use.
Thaw the pre-filled syringes of VeraSeal within the sterile field using a thermostatically controlled sterile water bath at 37 ± 2 °C by following the procedure below:
NOTE: Once the VeraSeal blisters are opened, use the product immediately. Use aseptic technique to avoid potential contamination due to improper handling, and carefully follow the procedure described below. Do not remove the syringe Luer cap until thawing is complete and the double applicator is ready to be connected.

1. Open the blister and make the syringe holder with pre-filled syringes of VeraSeal available to a second person for transfer to the sterile field. The exterior of the blister must not come into contact with the sterile field. See Figure 1.
2. Place the syringe holder with pre-filled syringes directly into the sterile water bath, ensuring it is completely submerged. See Figure 2.
3. At 37 °C, the required time is approximately 5 minutes for 2 mL, 4 mL, 6 mL and 10 mL packs; do not leave the packs in the water bath for longer than 10 minutes. The water bath temperature must not exceed 39 °C.
4. After thawing, dry the syringe holder with pre-filled syringes using a sterile surgical gauze. Ensure that the pre-filled syringes of VeraSeal are completely thawed. After thawing, the solutions should appear clear to slightly opalescent and colourless to light yellow. Do not use solutions that appear cloudy or contain particulate matter. Use VeraSeal immediately and discard any unused contents.

• Instructions for connecting
  1. Open the blister and make the double applicator and the two additional airless spray tips of VeraSeal available to a second person for transfer to the sterile field. The exterior of the blister must not come into contact with the sterile field.
  2. Hold the VeraSeal syringe holder with the syringe Luer caps facing upwards. See Figure 3.
  3. Unscrew and discard the Luer caps from the fibrinogen and thrombin syringes. See Figure 3.
  4. Hold the syringe holder with the Luer caps facing upwards. To remove air bubbles from the syringes, gently tap the side of the syringe holder one or two times while holding it vertically, and gently press the plunger to expel air. See Figure 4.
  5. Connect the double applicator. See Figure 5. NOTE: Do not press the plunger during connection or before intended use, as the two biological components would be premixed in the airless spray tip, forming a fibrin clot that would prevent delivery. See Figure 6.
  6. Tighten the Luer locks and ensure the double applicator is securely attached. The device is now ready for use.

• Administration
  Apply VeraSeal using the provided syringe holder and plunger. Apply VeraSeal using the double applicator provided with the product. Other application tips bearing the CE mark (including devices for laparoscopic and open surgery) specifically intended for use with VeraSeal may also be used. When using the provided double applicator, follow the connection instructions described above. When using other application tips, follow the instructions provided for their use.

Airless spray application

1. Grasp the double applicator and bend it into the desired position. The tip will retain its shape.
2. Position the airless spray tip at least 2 cm away from the target tissue. Apply steady, even pressure on the plunger to deliver the fibrin-based tissue adhesive. Increase the distance as needed to achieve the desired coverage of the treatment area.
3. If delivery is interrupted for any reason, replace the airless spray tip before resuming application, as a fibrin clot may form inside the airless spray tip. To replace the airless spray tip, remove the device from the patient and unscrew the used tip. See Figure 7. Place the used airless spray tip away from spare tips. Clean the end of the applicator with a dry or moist sterile surgical gauze. Then attach a new airless spray tip provided in the package and ensure it is securely applied before use. NOTE: The red indicator will not be visible if the airless spray tip is correctly connected. See Figure 8. NOTE: Do not continue pushing the plunger in an attempt to clear a fibrin clot inside the airless spray tip, as this may render the applicator unusable. NOTE: Do not cut the double applicator to avoid exposing the internal wire.

Drip-by-drip application

1. Unscrew the airless spray tip from the spray and drip tip to remove it. See Figure 7.
2. Grasp the double applicator and bend it into the desired position. The tip will retain its shape.
3. During drip-by-drip application, hold the end of the drip tip as close as possible to the tissue surface without touching it.
4. Apply individual drops onto the surface to be treated. To prevent uncontrolled coagulation, allow the drops to separate from each other and from the end of the drip tip. NOTE: Do not reconnect a drip tip once it has been removed from the adapter; otherwise, a clot may form inside the tip, rendering the applicator unusable.

• Disposal
  Unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.

Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8