Evarrest - patient leaflet, side effects, dosage

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCES AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) of the biological active substance(s)

Human Fibrinogen and Human Thrombin:

Omrix Biopharmaceuticals Ltd.

Plasma Fractionation Institute (Omrix-PFI), MDA Services Center

Sheba Medical Center

Ramat Gan 5262000

POB 888

Kiryat Ono 5510801

Israel

Human Fibrinogen:

Omrix Biopharmaceuticals Ltd.

Jerusalem Plant (Omrix-JP)

5 Kiryat Hamada St., Ramot Meir Building Har-Hotzvim P.O.B. 45075 Jerusalem 9777605

Israel

Name and address of the manufacturer(s) responsible for batch release Omrix Biopharmaceuticals N.V. rjK

Leonardo Da Vincilaan 15

1831 Diegem

Belgium

Medicinal products on “restricted” medical prescription, reserved for use in certain specialised areas (see Annex I: Summary of Product Characteristics, section 4.2).

• Official batch release

In accordance with Article 114 of Directive 2001/83/EC, the official batch release will be undertaken by a state laboratory or a laboratory designated for that purpose.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION

• Periodic safety update reports

The requirements for submission of periodic safety update reports for this medicinal product are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal.

• D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT

• Risk Management Plan (RMP)

The Marketing Authorization Holder (MAH) shall perform the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:

• At the request of the European Medicines Agency;
• Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE PACKAGING

Carton (10.2 cm x 10.2 cm, 5.1 cm x 10.2 cm) and Foil Sachet (10.2 cm x 10.2 cm)

• 1. NAME OF THE MEDICINAL PRODUCT

EVARREST Sealant Matrix

• 2. STATEMENT OF ACTIVE SUBSTANCE(S)

EVARREST contains per cm2

Human Fibrinogen

Human Thrombin

• 3. LIST OF EXCIPIENTS

Excipients:

Composite Matrix (Polyglactin 910 and oxidised regenerated cellulose)

Arginine hydrochloride

Glycine

Sodium chloride

Sodium citrate

Calcium chloride

Human albumin

Mannitol

Sodium acetate

• 5. METHOD AND ROUTE(S) OF ADMINISTRATION

For epilesional use.

Read the package leaflet before use.

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

• 7. OTHER SPECIAL WARNING(S), IF NECESSARY

• 8. EXPIRY DATE

EXP

• 9. SPECIAL STORAGE CONDITIONS

Do not store above 25°C. Do not freeze.

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

Any unused product or waste material should be disposed of in accordance with local requirements.

Justification for not including Braille accepted.

• 17. UNIQUE IDENTIFIER-2DBARCODE 2D barcode carrying the unique identifier included.

• 18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC: {number} SN: {number} NN: {number}

PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

Foil Sachet (5.1 cm x 10.2 cm)

• 1. NAME OF THE MEDICINAL PRODUCT

EVARREST Sealant Matrix

EVARREST contains per cm2

Human Fibrinogen 8.1 mg

Human Thrombin 40 IU

Contains one sealant matrix (5.1 cm x 10.2 cm)

EU/1/13/868/002

Package leaflet: Information for the patient

EVARREST Sealant Matrix

Human Fibrinogen / Human Thrombin

V This medicine is subject to additional monitoring. This will allow quick identification of new safetyinformation. You canhelp by reporting any side effects you may get. See the end of section 4 for how to report side effects.

Read all of this leaflet carefully before this medicine is used to treat you, 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.

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 is in this leaflet

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

What EVARREST is and what it is used for

EVARREST is a combination product mad 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.

2. What you need to know before you are treated with EVARREST:

Your surgeon must not treat you with EVARREST in the following circumstances:

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.

Warnings and precautions

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

Allergic-type hypersensitivity reactions are possible. Signs of such reactions include hives, rash, tightness of the chest, wheezing, drop in blood pre rapid onset). If these symptoms occur during surg 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.

Children and adolescents

EVARREST is not recommended for use in children and adolescents under 18 years of age.

Other medicines and EVARREST

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

Pregnancy, breast-feeding and fertility

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.

EVARREST contains sodium

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.

• 3. How EVARREST is used

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.

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.

4.

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.

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).

Reporting of side effects

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.

• 5. How EVARREST is stored

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.

6. Contents of the pack and other information

What EVARREST contains – 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

What EVARREST looks like and contents of the pack

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.

Marketing Authorisation Holder and Manufacturer

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 was last revised in MM/YYYY

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:

.

This leaflet is available in all EU/EEA languages on the European Medicines Agency website.

The following information is intended for healthcare professionals only:

Instructions for Use

Read this before you open the package

Handling of EVARREST

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.

Storage of EVARREST

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.

Application of EVARREST

For epilesional use only. EVARREST is to be applied with approximately 3 minutes of firm manual compression.

• 1. 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.

• 2. 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.

• 3. 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.

• 4. 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.

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.

• 6. 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.

  
  

• 7. The application site should be monitored intraoperatively to verify that haemostasis is maintained.

Re-Treatment

• 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.
• 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.