Raplixa - patient leaflet, side effects, dosage

6.6 Instructions for use and handling and special precautions for disposalRaplixa is a pre-mixed, ready to use ble

rombin 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 that is applied onto the surgical bleeding site directly from the vial or using the RaplixaSpray device. The Raplixa should be stored at controlled, ambient room temperature. The outer aluminium foil sachet may be opened in a non-sterile operating area. The vial must be opened in a sterile field.

plication: direct application of Raplixa to the bleeding tissue followed by application of the gelatin sponge or application of Raplixa first to a gelatin sponge and application of the sponge to the bleeding tissue; or application of the Raplixa powder by using the RaplixaSpray device followed by the application of the gelatin sponge.

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 product should only be administered according to the instructions and with the devices recommended for this product.

The initial amount of the product to be applied at a chosen anatomic site or target surface area should be sufficient to entirely cover the intended application area with a thin layer of Raplixa which is then covered by an absorbable gelatin sponge (saline-wetted). The application can be repeated, if necessary.

When using the RaplixaSpray device

Take the vial and device out of their respective pouches maintaining sterility. Connect the RaplixaSpray device to the RaplixaReg air pressure regulator or CO2 pressure regulator and thereby to the medical air or CO2 gas supply set to a pressure setting of 1.5 bar (22 psi). Hold the vial upright, shake gently and remove the aluminium cap and rubber stopper.

Connect the vial to the device by inverting the device over the upright vial and pushing the vial into place. 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.

The pressure should be within the range recommended by ProFibrix. Spray application of Rapli only be done using the provided spray application accessories and the pressure should not excee (22 psi).

Application must be within 2 hours after connecting the vial to the device. The comes with the rigid nozzle attached, which can be easily removed and the flex depending on the intended use and surgeon preference.

To avoid the risk of potentially life-threatening air embolism, it is recommended that Raplixa should be sprayed using pressurised CO2. Raplixa may also be used with medical air. See section 4.4.

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.

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

• 7. MARKETING AUTHORISATION HOLDER

  
  

Mallinckrodt Pharmaceuticals d Ltd

College Business & Technology Park Cruiserath Blanchardstown Dublin 15 Ireland

• 8. MARKETING AUTHORISATION NUMBER(S)

EU/1/14/985/001

EU/1/14/985/002

EU/1/14/985/003

• 9. DATE OF FIRST AUTHORISATION/RE­NEWAL OF THE AUTHORISATION

Date of first authorisation: 19 March 2015

LOGICAL ACTIVE SUBSTANCES AND E FOR BATCH RELEASE

CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND

E USE OF THE MEDICINAL PRODUCT

• A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCES AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers of the biological active substances

CSL Behring GmbH

Emil-von-Behring-StraBe 76

35041 Marburg

Germany

CSL Behring GmbH

Goerzhaeuser Hof 1

35041 Marburg (Stadtteil Michelbach)

Germany

Name and address of the manufacturer responsible for batch release

Nova Laboratories Limited

Martin House, Gloucester Crescent, Wigston,

Leicester, Leicestershire, LE18 4YL,

United Kingdom

• B. CONDITIONS OR RESTRICTIONS REGARDING

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product Characteristics, section 4.2).

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.

REQUIREMENTS OF THE MARKETING

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 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.

• Additional risk minimisation measures

Prior to launch of Raplixa in each Member State the Marketing Authorisation Holder (MAH) must agree about the content and format of the educational programme, including communication media, distribution modalities, and any other aspects of the programme, with the National Competent Authority.

The educational programme is aimed at increasing awareness about the risk of air or gas embolism with the use of Raplixa spray device and providing instructions for the correct usage of pressure regulators.

The MAH shall ensure that in each Member State where Raplixa who are expected to use Raplixa are provided with the following

• The Summary of Product Characteristics (SmPC)
• Guide for healthcare professionals

PARTICULARS TO APPEAR ON THE OUTER PACKAGING CARTON

1. NAME OF THE MEDICINAL PRODUCT

Raplixa sealant powder

Keep out of the sight and reach of children.

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

• 8. EXPIRY DATE

EXP

• 9. SPECIAL STORAGE CONDITIONS

Store between + 2 °C to + 25 °C.

Once the vial is opened, use within 2 hours

Sterile

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

Any unused product should be discarded in accordance with local require

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Mallinckrodt Pharmaceuticals Ireland Ltd

College Business & Technology Park, Cruiserath, Blanchardstown, Dublin 15, Ireland

___:zP ___________

• 12. MARKETING AUTHORISATION NUMBER(S) _________________

EU/1/14/985/001

EU/1/14/985/002

EU/1/14/985/003

• 16. INFORMATION IN BRAILLE

Justification for not including Braille accepted.

• 17. UNIQUE IDENTIFIER – 2D BARCODE

  2D barcode carrying the unique identifier included.

  
  

  18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

  
  

  PC:

  SN:

  NN:

  
  
  
  

PARTICULARS TO APPEAR ON THE OUTER PACKAGING ALUMINIUM-BONDED FOIL SACHET

1. NAME OF THE MEDICINAL PRODUCT

Raplixa sealant powder

Keep out of the sight and reach of children.

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

• 8. EXPIRY DATE

EXP

• 9. SPECIAL STORAGE CONDITIONS

Store between + 2 °C to + 25 °C.

Once the vial is opened, use within 2 hours

Sterile

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

Any unused product should be discarded in accordance with local require

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Mallinckrodt Pharmaceuticals Ireland Ltd

College Business & Technology Park, Cruiserath, Blanchardstown, Dublin 15, Ireland

___:zP ___________

• 12. MARKETING AUTHORISATION NUMBER(S) _________________

EU/1/14/985/001

EU/1/14/985/002

EU/1/14/985/003

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted.

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS Vial label

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Raplixa sealant powder

What Raplixa is and what it is used for

2. What you need to know before you are treated with Raplixa

Warnings and precautions

• 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 t e of the spray device at higher than recommended pressures and/or in close proximity to the tissue ace. 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) sho ly be used if it is

possible to accurately judge the spray distance.

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

disease or haemolytic anaemia).

Children and adolescents

Raplixa has not been evaluated for safety and effectiveness in children.

Other medicines and Raplixa

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

Pregnancy and breast-feeding

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.

3. How to Use Raplixa

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.

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:

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.

Kgr

4. Possible side effects

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

5. How to store Raplixa

Keep this medicine out of the sig

Do not use this medicine after 2 hours of opening the vial. Store Raplixa powder via Do not use Raplixa if

What Raplixa contains

– 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.

Table 1: Composition of Raplixa (per gram powder)

The other ingredients are trehalose, calcium chloride, albumin, sodium chloride, sodium citrate, L-arginine hydrochloride.

What Raplixa looks like and contents of the pack

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 and Manufacturer

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 4Y

This leaflet was last approved in 12/2016.

Detailed information on this medicine is available on the European.

The following is intended for healthcare professional

ogen supplied as a ready to use dry-powder fibrin

Raplixa. Raplixa is applied onto the surgical bleeding ray delivery device, or onto a moistened gelatin sponge

ite. Raplixa and the device should be stored at controlled,

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 plixa based on the size of the bleeding surface area to be treated is shown in the

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 mai

The Raplixa spray device is connected to the Raplixa 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 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.

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 con

The Raplixa spray device comes with t nozzle attached depending on the int

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.

Disposal

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

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