Evarrest
human fibrinogen, human thrombin
Human Fibrinogen / Human Thrombin
This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.
Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor.
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.
What EVARREST is and what it is used for
What you need to know before you are treated with EVARREST
How EVARREST is used
Possible side effects
How to store EVARREST
Contents of the pack and other information
Medicinal product no longer authorised
EVARREST is a combination product made from an absorbable material (Matrix) coated with human fibrinogen and human thrombin.
Fibrinogen is a protein extracted from the blood that forms a fibrin clot when acted upon by the enzyme thrombin. When the dry powder coating of EVARREST is wetted, the thrombin acts on the fibrinogen to rapidly form a clot. The fibrin clot becomes embedded in the Matrix which enables EVARREST to stick firmly to the surrounding tissue.
EVARREST is applied during surgical operations in adult subjects, to stop bleeding and oozing during the operation. It is applied directly onto tissue where it sticks firmly and stops bleeding. It is left in place after the operation and is absorbed by the body.
EVARREST must not be applied inside blood vessels.
You must not be treated with EVARREST if you are allergic to human fibrinogen or human thrombin or to any of the other ingredients of this medicine (listed in section 6).
EVARREST must not be used to repair injuries to the wall of large arteries or veins where the product is exposed to constant blood flow and pressure.
EVARREST must not be used in closed spaces (for example, in, around, or next to openings or passages in the bone or other restricted areas around bone) where it could swell and compress nerves or blood vessels.
EVARREST must not be used in the presence of active infection or in contaminated areas of the body because infection may occur.
Talk to your surgeon before you are treated with EVARREST.
Applications for which adequate data are not available
The use of EVARREST has not been studied in the following procedures, and there is therefore no information to show that it would be effective:
surgery to the brain or spinal cord
controlling bleeding in the stomach or intestines by applying the product through an endoscope (tube)
sealing surgical repairs to the intestines.
Foreign body reactions
As with any product which is implanted, the body may develop a reaction to the foreign material. This could result in problems with healing. EVARREST should only be used in a single layer with an
overlap of approximately 1 to 2 cm onto non-bleeding tissue to help it stick to the bleeding area. The
size of EVARREST should be limited to what is necessary to stop bleeding.
Hypersensitivity reactions
Medicinal product no longer authorised
Allergic-type hypersensitivity reactions are possible. Signs of such reactions include hives, rash, tightness of the chest, wheezing, drop in blood pressure, and anaphylaxis (a severe reaction with a
rapid onset). If these symptoms occur during surgery, the use of the product should be stopped
immediately.
Transmission of infectious agents
When medicines are made from human blood or plasma, certain measures are put into place to prevent infections being passed on to patients. These include:
careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded.
the testing of each donation and pools of plasma for signs of viruses/infections.
the inclusion of steps in the processing of the blood and plasma that can inactivate or remove viruses.
Despite these measures, when medicines prepared from human blood or plasma are given, the possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging viruses, or other types of infections.
The measures taken in the manufacture of fibrinogen and thrombin are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, and for the non-enveloped virus, hepatitis A. 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 (foetal infection) and for individuals whose immune system is depressed or who have some types of anaemia (e.g., sickle cell disease or haemolytic anaemia).
It is strongly recommended that every time you are treated with EVARREST, the name and batch number of the medicine are recorded in order to maintain a record of the batches used.
EVARREST is not recommended for use in children and adolescents under 18 years of age.
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
There is not enough information available to know whether any particular risks are associated with the use of EVARREST during pregnancy or whilst breast-feeding, or whether it could affect fertility. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.
This medicine contains up to 3.0 mmol (68.8 mg) sodium in each EVARREST sealant matrix. This should be taken into consideration by patients on a controlled sodium diet.
The surgeon will apply EVARREST during your operation. It is applied by pressing firmly onto bleeding tissue for approximately 3 minutes. EVARREST is activated upon contact with blood or other fluid and will stick firmly to the tissue. It is left in place and is absorbed by the body in approximately 8 weeks.
Medicinal product no longer authorised
EVARREST can be cut to the size and shape required to fit the size of the bleeding area. The amount of EVARREST that will be applied depends on the surface area and location of the bleeding site to be treated during the operation. EVARREST should only be used in a single layer. Up to the equivalent of two 10.2 cm x 10.2 cm units or four 5.1 cm x 10.2 cm units should be used if needed to cover the entire bleeding area, with an overlap of approximately 1 to 2 cm. If bleeding still occurs, the EVARREST sealant matrix can be removed, and a new one can be applied.
The total amount of EVARREST left in the body after the operation should not exceed the size of two
10.2 cm x 10.2 cm sealant matrices or four 5.1 cm x 10.2 cm sealant matrices.
Like all medicines, this medicine can cause side effects, although not everybody gets them. The following adverse events which occurred during clinical studies were considered to be related to the use of EVARREST:
Most Serious Side Effects
Bleeding (haemorrhage)
From the connection of two vessels (anastomotic haemorrhage); the frequency was uncommon (may affect up to 1 in 100 people).
From the stomach (intra-abdominal haemorrhage); the frequency was uncommon (may affect up to 1 in 100 people).
During surgery (operative haemorrhage); the frequency was uncommon (may affect up to 1 in 100 people).
After surgery (post-procedural haemorrhage); the frequency was uncommon (may affect up to 1 in 100 people).
Blood clot (thromboembolism)
In the veins, particularly of the legs (deep vein thrombosis)
In the arteries supplying the lungs (pulmonary embolism)
The frequency of both of these effects was uncommon (may affect up to 1 in 100 people).
Unintentional fluid intake into the airway (aspiration), build up of excess fluid in the cavity surrounding the lungs; the frequency was uncommon (may affect up to 1 in 100 people).
Accumulation of fluid in the stomach, swelling of the stomach; the frequency was uncommon (may affect up to 1 in 100 people).
Accumulation of fluid in the pancreas: the frequency was uncommon (may affect up to 1 in 100 people).
Increase in the levels of fibrinogen in the blood: the frequency was uncommon (may affect up to 1 in 100 people).
If you experience any symptoms such as vomiting with blood, blood in your stool, blood in your draining tube from your abdomen, swelling or skin discolouration in your extremities, chest pain and shortness of breath, and/or any other symptoms related to your surgery, please contact your doctor or surgeon immediately.
Medicinal product no longer authorised
EVARREST contains the components of fibrin sealant. Fibrin sealants may, in rare cases (up to 1 in 1,000 people), cause an allergic reaction. If you experience an allergic reaction you might have one or more of the following symptoms: swelling under the skin (angioedema), skin rash, hives or wheals (nettle-rash), tightness of the chest, chills, flushing, headache, low blood pressure, lethargy, nausea, restlessness, increased heart rate, tingling, vomiting, or wheezing. If you experience any of these symptoms after surgery you should consult your doctor or surgeon.
There is a also a theoretical possibility that you could develop antibodies to the proteins in EVARREST, which could potentially interfere with blood clotting. The frequency of this type of event is not known (cannot be estimated from available data).
If you get any side effects, talk to your doctor or surgeon. 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.
EVARREST must be kept out of the sight and reach of children.
EVARREST must not be used after the expiry date which is stated on the foil sachet as well as the carton after EXP. The expiry date refers to the last day of that month.
EVARREST must not be stored above 25°C and must not be frozen.
EVARREST must be kept dry at all times prior to application to avoid pre-activation.
The foil sachet protects EVARREST from moisture and from microbiological contamination.
The active substances are as follows:
Human fibrinogen (8.1 mg/cm2)
Human thrombin (40 IU/ cm2)
The other ingredients are:
Composite Matrix (Polyglactin 910 and oxidised regenerated cellulose)
Arginine hydrochloride
Glycine
Sodium chloride
Sodium citrate
Calcium chloride
Human albumin
Mannitol
Sodium acetate
EVARREST is presented as a sealant matrix which is 10.2 cm x 10.2 cm in size. Pack size of 1 and as sealant matrices which are 5.1 cm x 10.2 cm in size, Pack size of 2.
Medicinal product no longer authorised
Omrix Biopharmaceuticals N.V. Leonardo Da Vincilaan 15
1831 Diegem Belgium
Telephone: +32 2 746 30 00
Telefax: + 32 2 746 30 01
For any information about this medicine, please contact the Manufacturer: Pharmacovigilance Department
Omrix Biopharmaceuticals Ltd
Plasma Fractionation Institute (Omrix-PFI), MDA Services Center Sheba Medical Center
Ramat Gan 5262000
POB 888
Kiryat Ono 5510801 Israel
Telephone: +972-3-5316512
Telefax: +972-3-5316590
This leaflet is available in all EU/EEA languages on the European Medicines Agency website.
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The following information is intended for healthcare professionals only:
Read this before you open the package
EVARREST comes ready to use in sterile packages and must be handled using sterile technique in aseptic conditions. Discard damaged packages as re-sterilisation is not possible.
To open the product, remove the foil sachet from the carton, carefully peel open the foil sachet avoiding contact with the inside of the foil or the white sterile tray containing EVARREST.
Remove the white sterile tray from the pouch and place onto the sterile field.
Hold the tray securely in the palm of the hand, ensuring that the side with the holes is facing upwards, and use the tabs on the side of the tray to remove the top of the tray with the other hand.
The lower portion of the tray contains EVARREST with the active side facing downwards. The active side is powdery in appearance. The non-active side has an embossed wave pattern.
Keep EVARREST dry after opening. The EVARREST sealant matrix can remain in the sterile field to be available for use throughout the procedure. EVARREST does not stick to gloves, forceps, or surgical instruments.
Medicinal product no longer authorised
Do not use after the expiry date stated on the carton and label. Keep out of sight and reach of children.
Do not store above 25°C. Do not freeze.
For epilesional use only. EVARREST is to be applied with approximately 3 minutes of firm manual compression.
Using sterile scissors, carefully cut EVARREST to the size and shape as necessary to fit and maintain contact with the bleeding area with an overlap of approximately 1 to 2 cm. Keep the powdery white-to-yellow colour active side of EVARREST facing down while in the tray.
Remove excess blood or fluid from the site of application if required to improve visibility. The bleeding source should be clearly identified and it must be ensured that EVARREST is applied directly onto the bleeding source by covering it completely. EVARREST can be used in an actively bleeding field.
Apply the active side of EVARREST to the bleeding area, allowing full contact with the tissue.
The product is activated upon contact with fluid, and adheres and conforms to tissue.
Apply an appropriately sized piece of EVARREST to adequately cover the entire bleeding area, with an overlap of approximately 1 to 2 cm onto non-bleeding tissue, to assist with adherence to the wound site.
5a) Hold dry or moist surgical gauze or laparotomy pads over EVARREST to achieve full contact with the bleeding surface.
Medicinal product no longer authorised
5b) To ensure haemostasis, immediately apply manual compression over the entire surface of the EVARREST (including the area of overlap) sufficient to stem all bleeding. Maintain compression for approximately 3 minutes, to control the bleeding.
Gently remove surgical gauze or laparotomy pads from the application site, without disrupting or dislodging EVARREST or the clot. Inspect EVARREST to verify that haemostasis has been achieved and to ensure that there is no crimping over the bleeding area. If not satisfied with the placement, remove EVARREST and use a new EVARREST sealant matrix. EVARREST will remain in place and adhere to the tissue, and is absorbable.
The application site should be monitored intraoperatively to verify that haemostasis is maintained.
Re-treatment may be required if there are folds, creases, or crimps in the EVARREST sealant matrix. If not satisfied with the placement of EVARREST, remove the used EVARREST sealant matrix and repeat the application procedure above with a new EVARREST sealant matrix.
If bleeding is due to insufficient coverage of the bleeding area, additional EVARREST sealant matrices may be applied. Apply in a single layer; ensure that the edges overalap (by approximately 1 to 2 cm) with the existing EVARREST sealant matrix.
If bleeding is due to incomplete adherence to the tissue (where bleeding persists from under the dressing), remove EVARREST sealant matrix and use a new one.
Medicinal product no longer authorised
If bleeding still occurs during or after the specified duration of compression, remove the used EVARREST sealant matrix and inspect the bleeding site. If no other primary haemostatic measures (i.e., standard surgical techniques) appear to be required, repeat the application procedure above with a new EVARREST sealant matrix.
Any unused product or waste material should be disposed of in accordance with local requirements.