solutions for tissue adhesives
human fibrinogen, human thrombin
1. What EVICEL is and what it is used for
EVICEL is a human fibrin glue, which is supplied in packs containing two separate bottles, each containing 1 ml, 2 ml, or 5 ml solution (human fibrinogen and human thrombin, respectively).
An applicator and suitable accessory tips are supplied separately.
Fibrinogen is a concentrate of coagulable protein and thrombin is an enzyme that causes the coagulable protein to coagulate. Therefore, when the two components are mixed, they coagulate instantly.
EVICEL is used in adults during surgery to reduce bleeding and leakage during and after surgery.
EVICEL can be used for vascular surgery and surgery on the posterior abdominal wall. EVICEL can also be used to support a watertight closure of the meninges (dura mater) in neurosurgery when other surgical techniques are insufficient.
It is dripped or sprayed on cut tissue, where it forms a thin layer that seals tissue and/or stops bleeding.
2. What you need to know before using 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, skin rash, chest tightness, wheezing, drop in blood pressure, and difficulty breathing. If these symptoms occur, the administration must be stopped immediately.
- EVICEL must not be applied intravascularly.
- EVICEL must not be used in endoscopic surgery. For laparoscopy, see the recommendations below.
- EVICEL must not be used to seal the suture line in the dura mater if the gaps after suturing are greater than 2 mm.
- EVICEL must not be used as an adhesive for fixing dural patches.
- EVICEL must not be used as tissue glue when it is not possible to suture the dura mater.
Warnings and cautions
- To avoid the risk of potentially life-threatening air or gas embolism, EVICEL should only be sprayed with pressurized CO 2 gas.
- Before applying EVICEL, the wound surface must be dried according to standard procedures (eg intermittent application with compresses, cotton swabs, use of suction devices).
- When EVICEL is applied during surgery, the surgeon must make sure that it is only applied to the tissue surface. EVICEL must not be injected into tissue or blood vessels, as this would cause clots that could be life-threatening.
- The use of EVICEL has not been studied in the following treatments and therefore there is no information to suggest that it would be effective in these treatments:
- gluing of tissue er
- operations on the brain or spinal cord except to support a watertight closure of the meninges (dura mater)
- to control gastrointestinal bleeding by applying the drug using an endoscope (tube)
- sealing of surgical repairs of intestines
- seal in transsphenoidal and otoneurosurgical operations
- It is not known whether radiation therapy can affect the effectiveness of fibrin glue when used as a seal of the suture line in neurosurgery
- The use of EVICEL in neurosurgery in patients treated concomitantly with implants or with dural patches has not been studied in clinical trials.
- The bleeding should be under control before EVICEL is applied to seal the dural suture line.
- EVICEL will be applied a thin layer. An excessive thickness of the clot layer can adversely affect the efficiency of the product and the wound healing process.
Life-threatening air or gas embolism has occurred when using spray devices that use a pressure regulator to apply EVICEL. The occurrence seems to be related to the fact that the spray device was used with a pressure above the recommended and/or very close to the tissue surface. Spray application of EVICEL should only be used if it is possible to make a correct assessment of the spray distance, especially during laparoscopy. Spray distance from tissue and pressure must be within the intervals recommended by the manufacturer (see the table in the section Instructions for use). When spraying EVICEL, monitor any changes in blood pressure, heart rate, oxygenation, and end-time CO 2as there is a risk that air or gas embolism may occur. Spray devices and accessory tips provide operating instructions with recommendations for pressure range and proximity to the tissue surface, which must be followed carefully.
- The surrounding areas must be protected so that EVICEL is only applied to the surface to be treated.
- As with all medicines that contain protein, you may experience hypersensitivity reactions of the allergic type. Signs of such reactions include hives, skin rash, chest tightness, wheezing, drop in blood pressure, and anaphylaxis (sudden hypersensitivity reaction ). If these symptoms occur, the administration should be discontinued immediately.
- When medicines are made from human blood or plasma, certain measures are taken to prevent the transmission of infection to your patients. These include accuracy in selecting blood and plasma donors to ensure that those who can carry the infection are excluded, as well as testing each donation and plasma pool for signs of viruses/infections. The manufacturers of these products also take steps in the preparation of blood and plasma, which inactivate or remove viruses. Despite these measures, the risk of transmission of infection can not be completely ruled out when administered medicinal products derived from human blood or plasma. This also applies to any unknown or new viruses and other types of infections.
The measures taken in the manufacture of fibrinogen and thrombin are considered to be effective for viruses with a lipid envelope, such as human immunodeficiency virus ( HIV ), hepatitis B virus and hepatitis C virus, and hepatitis A virus without an envelope. The measures taken may have limited value against parvovirus B19. Parvovirus B19 infection can be serious in pregnant women (fetal infection) and in people whose immune systems are impaired or who have certain types of anemia (eg sickle cell anemia or hemolytic anemia ).
Healthcare professionals will register the name of the medicine and the batch number to be able to trace a possible source of infection.
Children and young people
There are insufficient data to confirm the safety and efficacy of EVICEL in children and adolescents.
Other medicines and EVICEL
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription.
Pregnancy and breastfeeding
There is not enough information available to know if there are any specific risks associated with the use of EVICEL during pregnancy or breast-feeding. However, as EVICEL is used during a surgical procedure, you should discuss the general risks of the operation with your doctor if you are pregnant or breast-feeding.
3. How to use EVICEL
Your doctor will administer EVICEL while you are having surgery. During the operation, the doctor will drip or spray EVICEL on the operating tissue with the help of an applicator. The applicator makes it possible to administer an equal amount of EVICEL’s two components at the same time, and ensures that they are evenly mixed, which is important for the adhesive to have an optimal effect.
The amount of EVICEL that will be applied depends on the area of the tissue surface to be treated during the operation. It will be dropped on tissue one in very small amounts or sprayed in short bursts (0.1-0.2 ml) to give a thin, even layer. If the application of a single layer of EVICEL does not stop the bleeding completely, a second layer can be applied.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them. The following adverse reactions that occurred during clinical trials were considered to be related to the use of EVICEL:
The most serious adverse reaction was
- Aqueous fluid coming from your wound or nose (CSV leakage / cerebrospinal rhinorrhea )
- Headache, nausea, and vomiting (due to subdural hygroma, which is an accumulation of CSV in the subdural space)
- Fever or prolonged constipation, flatulence (due to abdominal abscess)The frequency of effects listed above was common ( may affect up to 1 in 10 people ).
- Numbness and pain in arms and legs, change in skin color (due to graft occlusion or thrombosis )The frequency of this effect was uncommon (may affect up to 1 in 100 people).
If you get any of the above symptoms or any other symptoms associated with your surgery, contact your doctor or surgeon immediately. If you do not feel well, tell your doctor immediately, even if the symptoms are different from those just described.
Other side effects are
Other side effects that have been reported are common in clinical trials with EVICEL, ie. may occur in up to 1 in 10 users) including meningitis, and accumulation of CSV fluid in the brain cavity ( hydrocephalus ). The frequency of all these effects was common.
Adverse reactions that were uncommon during clinical trials with EVICEL (ie may occur in up to 1 in 100 users) included infection, blood clotting (hematoma), swelling, decreased hemoglobin, and postoperative wound complications (including bleeding or infection ).
EVICEL is a fibrin glue. Fibrin glue in general can, in rare cases (up to 1 patient in 1,000 users) cause allergic reactions. If you suffer from an allergic reaction, you may have one or more of the following symptoms: skin rash, hives or hives, pressure over the chest, chills, redness, headache, low blood pressure, lethargy, nausea, restlessness, increased heart rate, tingling, vomiting or wheezing breath. No allergic reactions have been reported so far in patients treated with EVICEL.
There is also a theoretical possibility that you may develop antibodies to the proteins in EVICEL, which may interfere with blood coagulation. The frequency of this type of event is not known (cannot be determined with available data).
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 and carton after EXP.
The expiration date is the last day of the specified month.
The bottles must be stored upright.
Store in a freezer at -18 ° C or colder. Store the bottles in the outer carton. Sensitive to light. Do not freeze again.
After thawing, unopened bottles can be stored at 2 ° C ‑ 8 ° C and protected from light for up to 30 days, without being re-frozen during this time. The new expiration date at 2 ° C ‑ 8 ° C should be noted on the carton, but should not exceed the expiration date printed by the manufacturer on the carton and label. At the end of this period, the medicine must be used or discarded.
The fibrinogen and thrombin components are stable at room temperature for up to 24 hours. EVICEL must not be placed in the refrigerator after it has reached room temperature.
Once drawn up in the applicator, they must be used immediately. Discard unused product after 24 hours at room temperature.
6. Contents of the packaging and other information
Content declaration
The active substances are as follows:
Component 1: Human coagulable 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 the contents of the pack
Pack sizes
EVICEL is a human fibrin glue, which is delivered in a package containing two separate glass bottles, each containing 1 ml, 2 ml, or 5 ml of human fibrinogen and human thrombin, respectively.
EVICEL is available in the following pack sizes: 2 x 1 ml, 2 x 2 ml and 2 x 5 ml. Not all pack sizes may be marketed in all countries.
An applicator and suitable accessory tips are supplied separately.
Marketing Authorisation Holder
Omrix Biopharmaceuticals NV
Leonardo Da Vinci Avenue 15
B-1831 Diegem
Belgium
Tel: + 32 2 746 30 00
Fax: + 32 2 746 30 01
Manufacturer
Omrix Biopharmaceuticals Ltd
Plasma Fractionation Institute
Sheba Hospital, Tel Hashomer
Ramat Gan 5262000, Israel
Tel: + 972-3-5316512
Fax: + 972-3-5316590