Evicel - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package Leaflet: Information for the patient

EVICEL solutions for sealant

human fibrinogen

human thrombin

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.

• – 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 EVICEL is and what it is used for

• 2. What you need to know before you use EVICEL

• 3. How to use EVICEL

• 4. Possible side effects

• 5 How to store EVICEL

• 6. Contents of the pack and other information

1. What EVICEL is and what it is used for

EVICEL is a Human Fibrin Sealant which is supplied as a package containing two separate vials, each containing 1 ml, 2 ml or 5 ml of solution (Human Fibrinogen and Human Thrombin respectively).

An application device and appropriate accessory tips are supplied separately.

Fibrinogen is a concentrate of clottable protein and thrombin is an enzyme that causes clottable protein to coalesce. Thus, when the two components are mixed together they clot instantly.

EVICEL is applied in adults during surgical operations to reduce bleeding and oozing during and after the operation.

EVICEL can be used in blood vessel surgery and in surgery taking place on the posterior abdominal wall. EVICEL can also be used to support the watertight closure of the cerebral envelopes (dura mater) during neurosurgery when other surgical techniques are insufficient.

It is dripped or sprayed onto cut tissue where it forms a thin layer that seals the tissue and/or stops bleeding.

2. What you need to know before you use EVICEL

Do not use EVICEL

• If you are hypersensitive (allergic) to products made from human blood or to any of the other ingredients of EVICEL (listed in section 6). Signs of allergic reactions include hives, rash, tightness of the chest, wheezing, drop in blood pressure, and breathing difficulties. If these symptoms occur, the administration has to be discontinued immediately.
• EVICEL must not be applied intravascularly.
• EVICEL should not be used in endoscopic surgery. For laparoscopy, see recommendation­s below.
• EVICEL must not be used for sealing the suture line in dura mater if there are gaps of greater than 2 mm after suturing.
• EVICEL must not be used as a glue for the fixation of dural patches.
• EVICEL must not be used as a sealant when the dura mater cannot be sutured.

Warnings and precautions

• To avoid the risk of potentially fatal air or gas embolism EVICEL should be sprayed using pressurised CO2 gas only.
• Prior to applying EVICEL, the surface area of the wound needs to be dried by standard techniques (e.g. intermittent application of compresses, swabs, use of suction devices).
• When EVICEL is applied during surgery, the surgeon must ensure that it is only applied onto the surface of tissue. EVICEL must not be injected into tissue or blood vessels because it would cause clots which could be fatal.
• The use of EVICEL has not been studied in the following procedures, and there is therefore no information to show that it would be effective in these procedures:
• gluing tissues together
• surgery to the brain or spinal cord except for support of watertight closure of cerebral envelopes (dura mater)
• controlling bleeding in the stomach or intestines by applying the product through an endoscope (tube)
• sealing surgical repairs to the intestines
• sealing in transphenoidal and otoneurosurgical procedures
• It is not known whether radiation therapy could affect the effectiveness of fibrin sealant when used for suture line sealing during neurosurgery.
• Use of EVICEL during neurosurgery in patients who are also being treated with implants or with dural patches has not been evaluated in clinical studies.
• The bleeding should be controlled before EVICEL is used to seal the dural suture line.
• EVICEL will be applied as a thin layer. Excessive clot thickness may negatively interfere with the product’s efficacy and the wound healing process.

Life-threatening air or gas embolism has occurred with the use of spray devices employing a pressure regulator to administer EVICEL. This event 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. EVICEL spray application should only be used if it is possible to accurately judge the spray distance, especially during laparoscopy. Spray distance from tissue and pressure should be within the ranges recommended by the manufacturer (see table in section Instructions for Use). When spraying EVICEL, changes in blood pressure, pulse, oxygen saturation, and end tidal CO2 should be monitored because of the possibility of occurrence of air or gas embolism. Spray devices and accessory tips provide instructions for use with recommendations for pressure ranges and proximity to tissue surface, which should be carefully followed.

• Nearby areas should be protected to make sure that EVICEL is only applied onto the surface which is to be treated.
• As with any product containing proteins, allergic-type hypersensitivity reactions are possible. Signs of such reactions include hives, rash, tightness of the chest, wheezing, drop in blood pressure and anaphylaxis. If these symptoms occur, the administration has to be discontinued immediately.
• 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, and the testing of each donation and pools of plasma for signs of viruses/infections. Manufacturers of these products also include 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 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.

The measures taken in the manufacture of fibrinogen and thrombin are considered effective for lipid coated viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and the non-enveloped virus, hepatitis A. The measures taken may be of limited value against 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).

The healthcare professionals will record the name and batch number of the medicinal product in order to trace any possible infection source.

Children and adolescents

Limited paediatric data are available to support efficacy and safety of EVICEL in this population.

Other medicines and EVICEL

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, even those not prescribed.

Pregnancy and breast-feeding

There is not enough information available to know whether any particular risks are associated with the use of EVICEL during pregnancy or whilst breast-feeding. However, since EVICEL is used during a surgical operation, if you are pregnant or breast-feeding, you should discuss the overall risks of the operation with your doctor.

3. How to use EVICEL

The doctor treating you will administer EVICEL during surgery. During your operation, your doctor will drip or spray EVICEL onto raw tissue, using an application device. This device allows equal amounts of the two components of EVICEL to be administered at the same time, and ensures that they mix evenly, which is important for the sealant to have its optimal effect.

The amount of EVICEL that will be applied depends on the surface area of tissue to be treated during the operation. It will be dripped onto the tissue in very small amounts or sprayed in short bursts (0.1–0.2 ml), to produce a thin, even layer. If application of a single layer of EVICEL does not completely stop the bleeding, a second layer may be applied.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects which occurred during clinical studies were considered to be related to the use of EVICEL:

Most serious side effects

• – Watery fluid coming out of your wound or nose (CSF leakage/CSF rhinorrhea)

• – Headache, nausea, and vomiting (due to Subdural Hygroma, which is accumulation of CSF in the subdural space)

• – Fever, or prolonged constipation, flatulence (due to abdominal abscess)

The frequency of the effects listed above was common (may affect up to 1 in 10 people).

• – Numbness or pain in your extremities, change in skin colour (due to Graft Occlusion or Thrombosis) The frequency of this effect was uncommon (may affect up to 1 in 100 people).

5. How to store EVICEL

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 label as well as on the carton after EXP. The expiry date refers to the last day of that month.

The vials must be stored in an upright position.

Store in a freezer at –18°C or colder. Keep the vials in the outer carton in order to protect from light. Do not refreeze.

After thawing, unopened vials can be stored at 2°C-8°C and protected from light, for up to 30 days, without being frozen again during this period. The new expiry date at 2°C-8°C should be noted on the carton but should not exceed the expiry date printed by the manufacturer on the carton and label. At the end of this period the product has to be used or discarded.

The fibrinogen and thrombin components are stable at room temperature for up to 24 hours. Do not refrigerate EVICEL once it has reached room temperature.

Once drawn up into the application device, they must be used immediately. Discard unused product after 24 hours at room temperature.

6. Contents of the pack and other information

What EVICEL contains

The active ingredients are as follows:

Component 1: Human clottable protein containing mainly fibrinogen and fibronectin (50 – 90 mg/ml)

Component 2: Human thrombin (800 – 1,200 IU/ml)

Other ingredients are:

Component 1: arginine hydrochloride, glycine, sodium chloride, sodium citrate, calcium chloride, and water for injections.

Component 2: calcium chloride, human albumin, mannitol, sodium acetate, and water for injections.

What EVICEL looks like and contents of the pack

Pack sizes

EVICEL is a human fibrin sealant which is supplied as a package containing two separate glass vials. Each contains 1 ml, 2 ml or 5 ml solution of human fibrinogen and human thrombin, respectively.

EVICEL is available in the following pack sizes: 2 × 1 ml, 2 × 2 ml, and 2 × 5 ml. All pack sizes may not be marketed in all countries

An application device and appropriate accessory tips are supplied separately.

Marketing Authorisation Holder and Manufacturer

Omrix Biopharmaceuticals N.V.

Leonardo Da Vinci Laan 15

B-1831 Diegem

Belgium

Tel: + 32 2 746 30 00

Fax: + 32 2 746 30 01

This leaflet was last revised in

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

EVICEL comes in sterile packages and therefore it is important to use only undamaged packages which have not been opened (post-sterilisation is not possible).

Storage

The approved shelf life of EVICEL is 2 years storage at < –18oC. Do not use after the expiry date stated on the carton.

Within the 2 years shelf life, after thawing, unopened vials can be stored at 2oC – 8°C (in a refrigerator) and protected from light, for up to 30 days. The date on which refrigerator storage was started should be marked on the carton in the space provided. Do not re-freeze. The fibrinogen and thrombin components are stable at room temperature for up to 24 hours but when they have been drawn up into the administration device, they must be used immediately.

The vials must be stored in an upright position.

Do not use after the expiry date stated on the carton and label.

Keep out of sight and reach of children.

The application device should be stored at room temperature, separately from the fibrinogen and thrombin.

Thawing

The vials should be thawed in one of the following ways:

2°C-8°C (refrigerator): vials thaw within 1 day,

20°C-25°C (room temperature): vials thaw within 1 hour,

37°C (e.g., water bath, using aseptic technique, or by warming vials in the hand): vials should be thawed within 10 minutes and must not be left at this temperature for longer than 10 minutes or until fully thawed. The temperature must not exceed 37° C.

Before use, the product must reach 20°C-30°C.

Preparation

EVICEL should only be applied using the CE-marked EVICEL application device and optional use of a tip accessory to the device. Leaflets giving detailed instructions for use of EVICEL in conjunction with the application device and optional accessory tips are provided with the package of the application device and of the accessory tips. The accessory tips should only be used by persons adequately trained in laparoscopic, laparoscopic-assisted, or open surgical procedures. The product should only be reconstituted and administered according to the instructions and with the devices recommended for this product.

To avoid the risk of potentially life-threatening air or gas embolism EVICEL should be sprayed using pressurised CO2 only.

The solutions should be clear or slightly opalescent. Do not use solutions that are cloudy or have deposits. Draw the contents of the two vials into the application device, following the instructions for use in the device package. Both syringes should be filled with equal volumes, and should not contain air bubbles. No needles are involved in the preparation of EVICEL for administration.

Prior to applying EVICEL the surface area of the wound needs to be dried by standard techniques (e.g., intermittent application of compresses, swabs, use of suction devices).

Application by dripping

Keeping the tip of the applicator as close to the tissue surface as possible, but without touching the tissue during application, apply individual drops to the area to be treated. If the applicator tip becomes blocked, the catheter tip can be cut back in 0.5 cm increments.

Spray application

EVICEL must be sprayed using pressurised CO2 only.

Connect the short tube on the application device to the male luer-lock end of the long gas tube. Connect the female luer-lock of the gas tube (with the 0.2 gm bacteriostatic filter) to a pressure regulator. The pressure regulator should be used in accordance with the manufacturer’s in­structions.

When applying EVICEL using a spray device, be sure to use a pressure and a distance from tissue within the ranges recommended by the manufacturer:

The product should then be sprayed onto the surface of the tissue in short bursts (0.1–0.2 ml) to form a thin, even layer. EVICEL forms a clear film over the area of application.

When spraying EVICEL, changes in blood pressure, pulse, oxygen saturation, and end tidal CO2 should be monitored because of the possibility of occurrence of gas embolism.

Disposal

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

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