Raplixa
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 of the side effects talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.
What Raplixa is and what it is used for
What you need to know before you are treated with Raplixa
How to use Raplixa
Possible side effects
How to store Raplixa
Medicinal product no longer authorised
Contents of the pack and other information
The active ingredient fibrinogen is a concentrate of clottable protein; the other active ingredient thrombin is an enzyme that causes clottable protein to coalesce to form a plug.
Raplixa is applied during surgical operations, to reduce bleeding and oozing during and after the operation in adults. In combination with a gelatin sponge, Raplixa is applied or sprayed onto cut tissue where it forms a layer that helps to stop bleeding.
if you are allergic to human fibrinogen, human thrombin or any of the other ingredients of this medicine (listed in section 6)
directly inside a blood vessel
in endoscopic procedures (procedures that use an endoscope for viewing internal organs) or keyhole surgery
as a glue for the fixation of patches
as a glue for intestines (gastrointestinal anastomoses)
on severe arterial bleeds
When Raplixa is applied during surgery, the surgeon must ensure that it is only applied onto the surface of tissue. Raplixa must not be injected into blood vessels because it would cause clots which could be fatal.
Use of Raplixa has only been shown to arrest bleeding in surgery visualized through the incision (open surgery).
Raplixa 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 events have occurred with the use of other spray devices employing a pressure regulator to administer other fibrin sealants. This event occurs when an air or gas bubble or bubbles enter a vein or artery and block it. It is called an air or gas embolism. 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. The risk appears to be higher when fibrin sealants are sprayed with air as compared to CO2 and therefore cannot be excluded with Raplixa. The Raplixa spray device (RaplixaSpray) should only be used if it is possible to accurately judge the spray distance.
When applying Raplixa using a spray device, a defined pressure within the range recommended by the spray device manufacturer is to be used. In addition, the spray device should not be used closer than the recommended distances. When spraying Raplixa, safety will be monitored because of the possibility of occurrence of air or gas embolism. The spray device and the accessory nozzle are provided with instructions for use, which should be carefully followed.
Nearby areas should be protected to make sure that Raplixa is only applied onto the surface which is to be treated.
Medicinal product no longer authorised
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 HIV (human immunodeficiency virus), hepatitis B virus and hepatitis C virus. The measures taken may be of limited value against non-enveloped viruses as hepatitis A virus and parvovirus B19 (causing fifth disease). 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 (for example sickle cell disease or haemolytic anaemia).
It is strongly recommended that every time you receive a dose of Raplixa the name and batch number of the medicine are recorded in order to maintain a record of the batches used.
Raplixa has not been evaluated for safety and effectiveness in children.
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Raplixa should not be administered during pregnancy and breast-feeding. There is not enough information
available to know whether any particular risks are associated with the use of Raplixa during pregnancy or whilst breast-feeding.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your
doctor or pharmacist for advice before taking this medicine.
The use of Raplixa is restricted to experienced surgeons who have been trained in the use of Raplixa. The surgeon treating you will administer Raplixa during surgery.
Prior to applying Raplixa the surface area of the wound needs to be dried by standard techniques (e.g.
intermittent application of compresses, swabs, use of suction devices).
There are three methods of administration of Raplixa:
Application of Raplixa straight from the vial to the bleeding site followed by the application of the gelatin sponge.
Application from the vial onto a wetted gelatin sponge and then applied to the bleeding site.
The third method is application of Raplixa onto the bleeding site using the recommended spray device followed by the application of the gelatin sponge.
Medicinal product no longer authorised
The amount of Raplixa that will be applied depends on the surface area to be treated during the operation and the severity of the blood loss. When Raplixa is applied directly to the surgical bleeding site, a thin layer should be used to cover the bleeding/oozing area completely. If application of a single layer of Raplixa does not completely stop the bleeding, more may be applied.
When applying Raplixa using the recommended spray device, your surgeon must be sure to use a pressure and a distance from tissue within the range recommended by the manufacturer as follows:
Surgery | Spray set to be used | Applicator tips to be used | Pressure regulator to be used | Recommended distance from target tissue | Recommended spray pressure |
Open surgery | 1 | 1 or 2 | RaplixaReg | 5 cm | 1.5 Bar (22 psi) |
When spraying Raplixa, 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.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
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: 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 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.
There is also a possibility that you could develop antibodies to the proteins in Raplixa, which could potentially interfere with blood clotting. The frequency of the type of event is not known (cannot be estimated from available data).
The following side effects have also been reported: Common side effects (may affect up to 1 in 10 people):
Itch
Difficulty sleeping
If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side
effects not listed in this leaflet. You can also report side effects directly via the national reporting system. By reporting side effects you can help provide more information on the safety of this medicine.
HPRA Pharmacovigilance Earlsfort Terrace
IRL - Dublin 2
Tel: +353 1 6764971
Fax: +353 1 6762517
Medicinal product no longer authorised
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
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. Raplixa must be used within 2 hours of opening the vial.
Store Raplixa powder vials at 2 °C to 25 °C.
Do not use Raplixa if the seal on the vial has been tampered with.
The active substances in Raplixa are human plasma derived fibrinogen and human thrombin.
The composition of Raplixa per gram powder is provided in Table 1.
Component | Target amount Quantity | Source | Function |
Human Fibrinogen | 79 mg/g | Human plasma | Active |
Human Thrombin | 726 IU/g | Human plasma | Active |
The other ingredients are trehalose, calcium chloride, albumin, sodium chloride, sodium citrate, L-arginine hydrochloride.
Raplixa is a ready to use, pre-mixed, sterile, white dry powder supplied in a vial containing either 0.5 g,
1 g or 2 g.
Marketing Authorisation Holder Mallinckrodt Pharmaceuticals Ireland Ltd
College Business & Technology Park, Cruiserath, Blanchardstown, Dublin 15, Ireland
Manufacturer
Nova Laboratories Limited
Martin House, Gloucester Crescent, Wigston, Leicester, Leicestershire, LE18 4YL, United Kingdom
Medicinal product no longer authorised
The following is intended for healthcare professionals only:
Raplixa is a pre-mixed, blend of thrombin and fibrinogen supplied as a ready to use dry-powder fibrin sealant in a glass vial containing 0.5 g, 1 g or 2 g of Raplixa. Raplixa is applied onto the surgical bleeding site directly from the vial or using the Raplixa spray delivery device, or onto a moistened gelatin sponge that is then applied to the surgical bleeding site. Raplixa and the device should be stored at controlled, ambient room temperature.
Prior to applying Raplixa the surface area of the wound needs to be dried by standard techniques (e.g. intermittent application of compresses, swabs, use of suction devices).
The gelatin sponges should be handled and used according to the manufacturer’s instructions in the package insert that accompanies the gelatin sponge.
The required dose of Raplixa based on the size of the bleeding surface area to be treated is shown in the table below:
Maximum Surface Area Direct Application from Vial | Maximum Surface Area Application Using RaplixaSpray | Raplixa Package Size |
25 cm² | 50 cm² | 0.5 g |
50 cm² | 100 cm² | 1.0 g |
Higher dosages up to 4g (including re-application and treatment of more than a single bleeding site) may be needed.
One of the following methods of application of Raplixa may be used based on the type of surgery, location and size and severity of the bleeding:
Direct application followed by gelatin sponge
Powder is applied directly from the vial onto the bleeding surface and then applied to a CE marked gelatin sponge cut to the appropriate size and apply manual pressure with sterile gauze.
Apply first to gelatin sponge
Powder is applied directly from the vial onto a saline-wetted CE marked gelatin sponge and then applied
to the bleeding site. When using a moistened gelatin sponge, a thin layer of Raplixa should be applied to the sponge immediately prior to application to the bleeding site.
Spray application using Raplixa spray device followed by gelatin sponge
Use Raplixa with the Raplixa spray device.
The vial and Raplixa spray device should be taken out of their respective pouches maintaining sterility. The Raplixa spray device is connected to the RaplixaReg pressure regulator and thereby to the medical
gas supply set to a pressure setting of 1.5 bar (22 psi).
The vial should be held upright, shake gently and the aluminium cap and rubber stopper should be removed.
The vial with powder is attached to the Raplixa spray device by inverting the device over the upright vial and pushing the vial into place.
Medicinal product no longer authorised
The Raplixa spray device is used to spray the powder on to the bleeding site and then the gelatin sheet is applied (see Instructions For Use for Raplixa spray device and gelatin sponge).
Application must be within 2 hours after connecting the vial to the device.
The Raplixa spray device comes with the rigid nozzle attached. This may be removed and the flexible nozzle attached depending on the intended use and surgeon preference.
Life threatening air or gas embolism has occurred with the use of spray devices employing pressure regulators to administer the fibrin sealant. 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. The risk appears to be higher when fibrin sealants are sprayed with air, as compared to CO2 and therefore cannot be excluded with Raplixa.
To avoid the risk of potentially life-threatening air embolism Raplixa is recommended to be sprayed using pressurised CO2. Raplixa may also be used with medical air.
When spraying Raplixa, 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.
When applying Raplixa using the Raplixa spray device, the pressure should be within the range recommended by ProFibrix. Spray application of Raplixa should only be done using the provided spray application accessories and the pressure should not exceed 1.5 bars (22 psi). Raplixa should not be sprayed at a distance closer than that recommended by the spray device manufacturer and in no case closer than 5 cm from the tissue surface.
Surgery | Spray set to be used | Applicator tips to be used | Pressure regulator to be used | Recommended distance from target tissue | Recommended spray pressure |
Open surgery | 1 | 1 or 2 | RaplixaReg | 5 cm | 1.5 Bar (22 psi) |
Medicinal product no longer authorised
Any unused product or waste material should be disposed of in accordance with local requirements.