Voncento (human coagulation factor VIII / human...) – Package leaflet - B02BD06

2. What you need to know before you use Voncento

Do not use Voncento

•If you are allergic to VWF or FVIII or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, nurse or pharmacist before taking Voncento.

•Allergic (hypersensitivity) reactions are possible. If symptoms of hypersensitivity occur, you should stop using the medicine immediately and contact your doctor. Your doctor should inform you of the early signs of hypersensitivity reactions. These include hives, generalised skin rash, tightness of the chest, wheezing, fall in blood pressure and anaphylaxis (a serious allergic reaction that causes severe difficulty in breathing, or dizziness).

•The formation of inhibitors (antibodies) is a known complication that can occur during treatment, which stops the treatment working properly. If your bleeding is not being controlled with Voncento, tell your doctor immediately. You should be monitored carefully for the development of inhibitors.

•If you have been told you have heart disease or are at risk for heart disease, tell your doctor or pharmacist.

•If for the administration of Voncento you will require a central venous access device (CVAD), the risk of CVAD-related complications including local infections, bacteria in the blood (bacteremia) and the formation of a blood clot in the blood vessel (thrombosis) where the catheter is inserted should be considered by your doctor.

•von Willebrand disease

If you have a known risk of developing blood clots, you must be monitored for early signs of thrombosis (blood clotting). Your doctor should give you treatment to prevent thrombosis.

Virus safety

When medicines are made from human blood or plasma, certain measures are put in place by the manufacturer 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 virus/infections,

•inclusion of steps in the processing of the blood or 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 are considered effective for so-called “enveloped” viruses such as human immunodeficiency virus (HIV, the AIDS virus), hepatitis B virus and hepatitis C virus (which cause inflammation of the liver), and for the “non-enveloped” hepatitis A virus (which also causes inflammation of the liver).

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 (as there is a risk of infection of the unborn child) and

•for individuals with a weakened immune system or with an increased production of red blood cells due to certain types of anaemia (e.g. sickle cell anaemia or haemolytic anaemia).

Your doctor may recommend that you consider being vaccinated against hepatitis A and B if you regularly/repeatedly receive human plasma-derived medicines such as Voncento.

It is strongly recommended that every time Voncento is given, you record the date of administration, the batch number and the injected volume in your treatment diary.

Children and adolescents

The listed warnings and precautions apply to adults, children and adolescents.

Other medicines and Voncento

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

Pregnancy and 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.

•During pregnancy and breast-feeding, Voncento should be given only if it is clearly needed.

Driving and using machines

Voncento does not affect your ability to drive and use machines.

Voncento contains sodium

The presentations 250 IU FVIII /600 IU VWF (5 ml solvent) and 500 IU FVIII /1200 IU VWF (5 ml solvent) contain up to 14.75 mg (0.64 mmol) sodium per vial.

The presentations 500 IU FVIII /1200 IU VWF (10 ml solvent) and 1000 IU FVIII /2400 IU VWF (10 ml solvent) contain up to 29.50 mg (1.28 mmol) sodium per vial.

Please take this into account if you are on a controlled sodium diet.

3.How to use Voncento

Your treatment should be monitored by a doctor who is experienced in the treatment of blood clotting disorders.

If your doctor thinks you could administer Voncento yourself, appropriate instructions will be provided to you by your doctor. Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.

Dose

The amount of VWF and FVIII you need to take and the duration of treatment depend on:

•the severity of your disease

•the site and intensity of the bleeding

•your clinical condition

•your body weight

(see also section “The following information is intended for healthcare professionals only”).

If you have been prescribed Voncento to use at home, your doctor will make sure that you are shown how to inject it and how much to use.

Follow the directions given to you by your doctor.

Use in children and adolescents

Dosing in children and adolescents aged < 18 years is based on body weight and is therefore generally based on the same instructions as for adults. In some cases, especially in younger patients, higher doses may be needed.

If you use more Voncento than you should

Five cases of overdose have been reported from clinical trials. No side effects have been associated with these reports. The risk of developing blood clots (thrombosis) cannot be excluded in case of an extremely high dose, especially in patients with VWD.

If you forget to use Voncento

•Proceed with your next dose immediately and continue at regular intervals as advised by your doctor.

•Do not take a double dose to make up for a forgotten dose.

If you stop using Voncento

Do not stop using Voncento without consulting your doctor.

Reconstitution and application

General Instructions

•The powder must be mixed with the solvent (liquid) and withdrawn from the vial under aseptic conditions.

•Voncento must not be mixed with other medicines, diluents or solvents except those mentioned in section 6.

•The solution should be clear or slightly opalescent, i.e. it might be sparkling when held up to the light but must not contain any obvious particles. After filtering or withdrawal (see below) the solution should be checked by eye, before it is used. Do not use the solution if it is visibly cloudy or if it contains flakes or particles.

•Any unused product or waste material should be disposed of in accordance with local requirements and as instructed by your doctor.

Reconstitution

Without opening the vials, warm the Voncento powder and the liquid to room or body temperature. This can be done either by leaving the vials at room temperature for about an hour, or by holding them in your hands for a few minutes.

DO NOT expose the vials to direct heat. The vials must not be heated above body temperature (37 ºC).

Carefully remove the protective caps from the vials, and clean the exposed rubber stoppers with an alcohol swab. Allow the vials to dry before opening the Mix2Vial package (which contains the filter transfer device), then follow the instructions given below.

1. Open the Mix2Vial package by peeling off the lid. Do not remove the Mix2Vial from the blister package!

2. Place the solvent vial on an even, clean surface and hold the vial tight. Take the Mix2Vial together with the blister package and push the spike of the blue adapter end straight down through the solvent vial stopper.

3. Carefully remove the blister package from the Mix2Vial set by holding at the rim, and pulling vertically upwards. Make sure that you only pull away the blister package and not the Mix2Vial set.

4. Place the product vial on an even and firm surface. Invert the solvent vial with the Mix2Vial set attached and push the spike of the transparent adapter end straight down through the product vial stopper. The solvent will automatically flow into the product vial.

5. With one hand grasp the product-side of the Mix2Vial set and with the other hand grasp the solvent-side and unscrew the set carefully counterclockwise into two pieces to avoid excessive build-up of foam when dissolving the product. Discard the solvent vial with the blue Mix2Vial adapter attached.

6.Gently swirl the product vial with the transparent adapter attached until the substance is fully dissolved. Do not shake.

7. Draw air into an empty, sterile syringe. While the product vial is upright, connect the syringe to the Mix2Vial´s Luer Lock fitting by screwing clockwise. Inject air into the product vial.

Withdrawal and Application

8. While keeping the syringe plunger pressed, turn the system upside down and draw the solution into the syringe by pulling the plunger back slowly.

9. Now that the solution has been transferred into the syringe, firmly hold on to the barrel of the syringe (keeping the syringe plunger facing down) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing counterclockwise.

Use the venipuncture kit supplied with the product, insert the needle into a vein. Let blood flow back to the end of the tube. Attach the syringe to the threaded, locking end of the venipuncture kit. The use of plastic disposable syringes is recommended as the ground glass surfaces of all-glass syringes tend to stick with solutions of this type. Inject/infuse the reconstituted solution slowly (at a rate not more than 6 ml per minute) into the vein following the instructions given to you by your doctor. Take care not to get any blood in the syringe containing the product.

In case large volumes of Voncento are required, it is possible to pool several vials of Voncento together, via a commercially available infusion set (e.g. a syringe pump for giving medicines into a vein). However, in these cases the initially reconstituted solution of Voncento should not be diluted any further.

Check yourself for any side effects that might happen straight away. If you have any side effects that might be related to the administration of Voncento, the injection or infusion should be stopped (see also section 2).

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4.Possible side effects

Like all medicines, Voncento can cause side effects, although not everybody gets them.

Please contact your doctor immediately in case of emergency:

•if you notice symptoms of allergic reactions (see below)

•if you notice that the medicine stops working properly

•if you notice any symptoms of an impaired perfusion in your extremities (e.g. cold and pale extremities) or vital organs (e.g. severe chest pain)

The following side effect has been observed very commonly (may affect more than 1 in 10 people):

•Headache

The following side effects have been observed commonly (may affect up to 1 in 10 people):

•FVIII inhibition: the medicine stops working properly (continuous bleeding). You may develop an inhibitor (neutralising antibody) to FVIII, in which case FVIII will not work properly any more. If this happens, you should stop using the medicine immediately and contact your doctor.

•Allergic reactions have been observed and may in some cases progress to a serious allergic reaction (anaphylaxis) that causes severe difficulty in breathing, dizziness or shock. Allergic reactions may include the following symptoms:

Swollen face, tongue, mouth or throat, difficulty in breathing and swallowing, hives, wheezing, burning and stinging where the infusion was given, chills, flushing, skin rash over the whole body, headache, fall in blood pressure, restlessness, faster heart beat, tightness of the chest (including chest pain and chest discomfort), back pain, tiredness (lethargy), nausea, vomiting, tingling. If this happens, you should stop using the medicine immediately and contact your doctor.

•Increase in body temperature

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu.

----------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

Posology

von Willebrand disease

It is important to calculate the dose using the number of IU of VWF:RCo specified. Generally, 1 IU/kg VWF:RCo raises the circulating level of VWF:RCo by 0.02 IU/ml (2 %).

Levels of VWF:RCo of > 0.6 IU/ml (60 %) and of FVIII:C of > 0.4 IU/ml (40 %) should be achieved.

On-demand treatment

Usually 40 - 80 IU/kg of VWF (VWF:RCo) corresponding to 20 - 40 IU FVIII:C/kg of body weight (BW) are recommended to achieve haemostasis.

An initial dose of 80 IU/kg VWF:RCo may be required, especially in patients with type 3 VWD where maintenance of adequate levels may require greater doses than in other types of VWD.

Prevention of haemorrhage in case of surgery:

For prevention of excessive bleeding during or after surgery the application should start 1 - 2 hours before the surgical procedure.

An appropriate dose should be re-administered every 12 - 24 hours. The dose and duration of the treatment depend on the clinical status of the patient, the type and severity of the bleeding, and both VWF:RCo and FVIII:C levels.

When using a FVIII-containing VWF product, the treating physician should be aware that continued treatment may cause an excessive rise in FVIII:C. After 24 - 48 hours of treatment, in order to avoid an excessive rise in FVIII:C, reduced doses and/or prolongation of the dose interval or the use of a VWF product containing a low level of FVIII should be considered.

Prophylaxis treatment

For long term prophylaxis in patients with VWD, a dose of 25 - 40 IU VWF:RCo /kg body weight should be considered at a frequency of 1 to 3 times per week. In patients with gastrointestinal bleeds or menorrhagia, shorter dose intervals or higher doses may be necessary. The dose and duration of treatment will depend on the clinical status of the patient, as well as their VWF:RCo and FVIII:C plasma levels.

Paediatric VWD population

Treatment of bleeding

Usually 40 - 80 IU/kg of von Willebrand factor (VWF:RCo) corresponding to 20 - 40 IU FVIII:C/kg of body weight (BW) are recommended in paediatric patients to treat a bleed.

Prophylaxis treatment

Patients aged 12 to 18 years old: Dosing is based on the same guidelines as for adults.

Patients aged <12 years old: Based on results from a clinical trial in which paediatric patients under 12 years of age were shown to have lower exposure of VWF, a prophylactic dose range of 40 – 80 IU VWF:RCo/kg body weight 1 to 3 times a week should be considered.

The dose and duration of treatment will depend on the clinical status of the patient, as well as their VWF:RCo and FVIII:C plasma levels.

Haemophilia A

It is important to calculate the dose using the number of IU of FVIII:C specified.

The dose and duration of the substitution therapy depend on the severity of the FVIII deficiency, on the location and extent of the bleeding and on the patient’s clinical condition.

The number of units of FVIII administered is expressed in International Units (IU), which is related to the current WHO standard for FVIII products. FVIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or preferably in International Units (relative to an International Standard for FVIII in plasma).

1 IU of FVIII activity is equivalent to that quantity of FVIII in 1 ml of normal human plasma.

On demand treatment

The calculation of the required dose of FVIII is based on the empirical finding that 1 IU FVIII per kg body weight raises the plasma FVIII activity by about 2 % of normal activity (in vivo recovery 2 IU/dl). The required dose is determined using the following formula:

Required units = body weight [kg] x desired FVIII rise [% or IU/dl] x 0.5.

The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case.

In the case of the following haemorrhagic events, the FVIII activity should not fall below the given plasma activity level (in % of normal or IU/dl) within the corresponding period. The following table can be used to guide dosing in bleeding episodes and surgery: