VONCENTO 250 IU/600 IU Proszek i rozpuszczalnik do roztworu do wstrzykiwań

Treść ulotki

1. Voncento 250 IU FVIII/600 IU VWF (5 ml solvent) powder and solvent for solution for
2. Voncento 500 IU FVIII/1200 IU VWF (10 ml solvent) powder and solvent for solution for
3. Voncento 500 IU FVIII/1200 IU VWF (5 ml solvent) powder and solvent for solution for
   1. What is Voncento and what is it used for
   2. What you need to know before you take Voncento
   3. How to use Voncento
   4. Possible side effects
   5. How to store Voncento
   6. Contents of the pack and other information

Voncento 250 IU FVIII/600 IU VWF (5 ml solvent) powder and solvent for solution for

injection/infusion

Voncento 500 IU FVIII/1200 IU VWF (10 ml solvent) powder and solvent for solution for

injection/infusion

Voncento 500 IU FVIII/1200 IU VWF (5 ml solvent) powder and solvent for solution for

injection/infusion
Voncento 1000 IU FVIII/2400 IU VWF (10 ml solvent) powder and solvent for solution for
injection/infusion
human coagulation factor VIII,
human von Willebrand factor

important information for you.

• If you have any doubts, ask your doctor, nurse or pharmacist.
• This medicine has been prescribed for you. Do not give it to other people, even if their symptoms are the same as yours, as it could be dangerous.
• If any side effects occur, including those not listed in this leaflet, tell your doctor, nurse or pharmacist. See section 4.
• 1. What Voncento is and what it is used for
• 2. What you need to know before you use Voncento
• 3. How to use Voncento
• 4. Possible side effects
• 5. How to store Voncento
• 6. Contents of the pack and other information

1. What is Voncento and what is it used for

Voncento contains the active substances called Human coagulation Factor VIII (FVIII) and Human von Willebrand Factor (VWF) derived from human plasma (the liquid part of the blood).
Voncento is used in all age groups to prevent or stop bleeding (haemorrhage) caused
by a deficiency of VWF in von Willebrand disease (VWD) and of FVIII in haemophilia A. Voncento
is only used when treatment with another medicine, desmopressin, is not effective on its own
or cannot be given.
VWF and FVIII are involved in blood coagulation. A deficiency of both factors
means that the blood does not clot as quickly as it should, resulting in an increased
tendency to bleed. Replacing VWF and FVIII with Voncento will temporarily correct
the blood coagulation mechanisms.
Since Voncento contains both Factor VIII and VWF, it is important to know which factor You
need most. Depending on whether you suffer from haemophilia A or VWD, your doctor will
prescribe Voncento with the specified number of units of FVIII or VWF.

2. What you need to know before you take Voncento

Do not use Voncento

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

Warnings and precautions
Traceability
It is strongly recommended that each time Voncento is administered, you record the date of
administration, the batch number and the amount of product injected in your therapeutic diary.
Ask your doctor, nurse or pharmacist before taking Voncento.

• Allergic reactions (hypersensitivity) are possible. If symptoms of hypersensitivity appear, immediately stop administering the medicine and consult your doctor.The doctor is required to inform you of what the early symptoms of a hypersensitivity reactionare. These include hives, widespread skin rash, a feeling of tightness in the chest, wheezing, hypotension and anaphylaxis (a severe allergic reaction that causes severe difficulty breathing or dizziness).
• The formation of inhibitors(antibodies) is a known complication that can occur during treatment with all factor VIII-based medicines. Inhibitors, especially at high levels, prevent the treatment from working properly and you or your child will be carefully monitored to check for the development of these inhibitors. If Voncento does not control bleeding in you or your child, inform your doctor immediately.
• If you know you have heart problems or are at risk of heart problems, tell your doctor or pharmacist.
• If a central venous access device (CVAD) needs to be used to administer Voncento, your doctor must consider the risk of CVAD-related complications, including local infections, bloodstream infections (bacteremia) and formation of a blood clot in the blood vessel (thrombosis) into which the catheter was inserted.
• Von Willebrand Disease If you are known to be at risk of developing blood clots, you will be closely monitored for early signs of thrombosis (blood clot formation). The doctor must give you treatment to prevent thrombotic episodes.

Viral safety
When medicines are made from human blood or plasma, certain measures are taken by the
manufacturer to prevent the risk of infections to patients. These include:

• careful selection of blood and plasma donors to exclude those at risk of transmitting infections,
• testing of individual donations and of plasma pools for the presence of viruses/infections,
• inclusion of steps in the blood or plasma processing that are capable of inactivating or removing viruses.

Despite these measures, when medicines prepared from human blood or plasma are
administered, the possibility of transmitting infections cannot be completely excluded. This
also applies to unknown or emerging viruses and other types of infections.
The measures taken are considered effective for so-called “enveloped” viruses, such as the
human immunodeficiency virus (HIV, the AIDS virus), hepatitis B virus and hepatitis C virus (which
cause liver inflammation), and for the “non-enveloped” hepatitis A virus (which also
causes liver inflammation).
The measures taken may have limited value against non-enveloped viruses, such as
parvovirus B19.
Infection with Parvovirus B19 can 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 increased red blood cell production due to a certain type of anemia (e.g. sickle cell anemia or hemolytic anemia).

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

Children and adolescents
The warnings and precautions mentioned apply to 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 breastfeeding

• If you are pregnant, breastfeeding, suspect you may be pregnant or are planning to become pregnant, ask your doctor or pharmacist for advice before using this medicine.
• During pregnancy and breastfeeding, Voncento should only be given if clearly indicated.

Driving and using machines
Voncenco does not affect your ability to drive or operate machinery.

Voncento contains Sodium
The 250 IU FVIII/600 IU VWF (5 ml solvent) and 500 IU FVIII/1200 IU VWF (5 ml
solvent) packs contain up to 14.75 mg of sodium per vial (main ingredient in
meal preparation / table salt). This is equivalent to 0.74% of the maximum recommended daily intake of sodium for an adult.
The 500 IU FVIII/1200 IU VWF (10 ml solvent) and 1000 IU FVIII/2400 IU VWF (10
ml solvent) packs contain up to 29.50 mg of sodium per vial (main ingredient in
meal preparation / table salt). This is equivalent to 1.48% of the maximum recommended daily intake of sodium for an adult.

3. How to use Voncento

Your treatment must be monitored by a doctor experienced in the treatment of blood coagulation disorders.
If your doctor believes that you can take Voncento on your own, you will be properly instructed.
Take this medicine following the doctor's instructions exactly at all times. If you have any doubts, consult your doctor.

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

• the severity of your condition
• the location and intensity of the bleeding
• your clinical condition
• your body weight (see also paragraph “The following information is intended exclusively for healthcare professionals”). If Voncento has been prescribed for you to use at home, your doctor will show you how to administer the infusion and how much product to use.

Follow the instructions provided by your doctor.
Use in children and adolescents
The dosage in children and adolescents < 18 years of age is established based on body weight and is therefore generally established according to the same instructions as adults. In some cases, especially in younger patients, higher doses may be necessary.
If you take more Voncento than you should
Five cases of overdose have been observed in clinical studies. No adverse effects were associated with these cases. However, the risk of developing blood clots (thrombosis) cannot be excluded in case of a high dosage, especially in patients with VWD.
If you forget to take Voncento

• Proceed with the next dose immediately and continue at regular intervals as recommended by your doctor.
• Do not take a double dose to make up for a missed dose.

If you stop treatment with Voncento
Do not stop treatment with Voncento without consulting your doctor.

Reconstitution and administration
General instructions

• The powder must be mixed with the solvent (liquid) and drawn from the vial under sterile conditions.
• Voncento must not be mixed with other medicines, diluents or solvents except those mentioned in paragraph 6.
• The solution should be clear or slightly opalescent, e.g. it may show some sparkle if exposed to light but should not contain any visible particles. After filtration and withdrawal (see below) the solution must be visually inspected before use. Do not use the solution if it is visibly cloudy or if it contains deposits or particles.
• Unused product and waste resulting from this medicine must be disposed of in accordance with local regulations and as specified by your doctor.

Reconstitution
Without opening the vials, bring both the Voncento powder and the solvent to room temperature or body temperature. This can be done by leaving the two vials at room temperature for about an hour or by holding them in your hands for a few minutes. DO NOT EXPOSE the vials directly to heat. The vials must not be brought to a temperature higher than body temperature (37 °C).
Carefully remove the protective caps from the vials and clean the surface of the rubber stoppers with an alcohol swab. Allow the vials to dry before opening the Mix2Vial package (which contains the transfer device with filter), then follow the instructions below.

1	1. Open the Mix2Vial package by detaching the closure. Do not remove the Mix2Vial from the package! o
2	c 2. Place the solvent vial on a flat and clean surface, holding the vial firmly. Take the Mix2Vial together with the entire package and push the blue terminal part into the solvent cap. m
3	r 3. Carefully remove the package from the Mix2Vial set by holding it by the edge and pulling it vertically upwards. a Make sure to pull only the outer package and not the F Mix2Vial set.
4	l 4. Securely place the product vial on a flat surface. Rotate the solvent vial upside down with the Mix2Vial set attached and push the transparent adapter through the cap of the vial containing the powder. Automatically, the solvent will be transferred into the vial containing the powder.
5	a n 5. Holding the product vial with the Mix2Vial set in one hand, grab the diluent vial with the other hand and carefully unscrew the set in a counterclockwise direction into its two components to avoid producing excessive foam when the product is diluted. Discard the solvent vial with the Mix2Vial adapter attached.
I 6	a 6. Gently rotate the vial with the transparent adapter until the powder is completely dissolved. Do not shake the vial.
a i z n e 7	7. Draw air into a sterile, empty syringe. Holding the product vial vertically, connect the syringe to the Luer Lock connector of the Mix2Vial set by screwing it clockwise and inject the air into the product vial.

Withdrawal and administration
Use the infusion set provided with the product, inserting the needle into a vein. Allow blood to flow back into the distal end of the cannula. Connect the syringe to the end of the infusion kit with the thread. It is recommended to use disposable plastic syringes as solutions of this type tend not to flow with the smooth surfaces of glass syringes. Inject/infuse the reconstituted solution slowly (at a rate of no more than 6 ml/minute) intravenouslyfollowing the instructions provided by your doctor. Be careful not to allow blood to flow back into the syringe containing the product.
If large volumes of Voncento are required, several vials of Voncento can be connected together using a commercially available infusion set (e.g. a syringe pump for administering drugs intravenously). However, in these cases, the initially reconstituted Voncento solution must not be further diluted.
Pay attention to any adverse effects that may occur during administration.
If you believe that one of these adverse effects may be related to the administration of Voncento, the injection or infusion must be stopped (see also paragraph 2).
If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

8	8. Keeping the syringe plunger pressed down, turn the system upside down and draw the solution into the syringe by slowly pulling back the plunger.
9	r 9. Now that the solution has been transferred to the syringe, firmly grasp the body of the syringe a (holding the syringe plunger facing down) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing it counterclockwise. l

4. Possible side effects

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

Contact your doctor immediately if:

• you notice symptoms of an allergic reactionIn some cases, it may progress to a severe allergic reaction (anaphylaxis) causing severe difficulty in breathing, dizziness or shock. Allergic reactions may include the following symptoms: swelling of the face, tongue, mouth or throat, difficulty breathing and swallowing, hives, wheezing, burning and stinging pain at the infusion site, chills, flushing, rash all over the body, headache, drop in blood pressure, restlessness, fast heartbeat, chest tightness (including chest pain and discomfort), back pain, fatigue (lethargy), nausea, vomiting, tingling.
• you notice a reduction in the drug's effectiveness (bleeding does not stop).

For children not previously treated with factor VIII-based medicines, the formation of
inhibitor antibodies (see section 2) may be very common (more than 1 in 10 patients);
however, in patients who have received previous treatment with factor VIII (more than
150 days of treatment) the risk is uncommon (less than 1 in 100 patients). If this happens,
the medicine for you or your child may stop working properly and you or your child
may experience persistent bleeding.
You may develop an inhibitor (neutralizing antibody) to VWF, in which case VWF will no
longer work correctly

• you notice any symptoms of impaired blood supply to the extremities (e.g.cold and pale hands and feet) or to vital organs (e.g. severe chest pain).There is a risk of blood clot formation (thrombosis), particularly in patients with known risk factors (see also section 2).

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

• Headache

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

• Increased body temperature

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

• Taste alteration (dysgeusia)
• Changes in liver function tests

Side effects in children and adolescents
It is expected that adverse reactions in children and adolescents will be the same as in adults

Reporting of side effects
If you get any side effects, talk to your doctor, nurse or pharmacist. You can also report side effects directly
through the national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Voncento

• 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 the packaging.
• Do not store at temperatures above 25 °C.
• Do not freeze.
• Voncerto does not contain preservatives, therefore the reconstituted product must be used immediately.
• If the reconstituted product is not administered immediately, the storage times and conditions before use are the responsibility of the user.
• Keep the vials in the packaging to protect the medicine from light.
• Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Voncento contains
The active ingredient is:
250 IU of FVIII and 600 IU of VWF per vial; after reconstitution with 5 ml of water for
injections, approximately 50 IU/ml FVIII and 120 IU/ml VWF are obtained.
500 IU of FVIII and 1200 IU of VWF per vial; after reconstitution with 10 ml of water
for injections, approximately 50 IU/ml FVIII and 120 IU/ml VWF are obtained.
500 IU of FVIII and 1200 IU of VWF per vial; after reconstitution with 5 ml of water for
injections, approximately 100 IU/ml FVIII and 240 IU/ml VWF are obtained.
1000 IU of FVIII and 2400 IU of VWF per vial; after reconstitution with 10 ml of water
for injections, approximately 100 IU/ml FVIII and 240 IU/ml VWF are obtained.
For further information see paragraph “The following information is intended exclusively

for healthcare professionals”.
The other ingredients are:
Calcium chloride, human albumin, sodium chloride, sodium citrate, sucrose, trometamol.
See paragraph 2 “Voncerto contains sodium”.
Solvent: Water for injections

Description of the appearance of Voncento and contents of the pack
Voncerto is supplied as a white powder together with the solvent for solution for injection/infusion.
The reconstituted solution should be from clear to slightly opalescent, e.g. it may sparkle when
exposed to light but should not contain visible particles.
The primary container of the product plus solvent consists of a glass vial with a rubber stopper, a plastic disc and an aluminium cap.
Pack sizes
A pack with 250 IU/600 IU or 500 IU/1200 IU contains:
1 vial with powder
1 vial with 5 ml of water for injections
1 transfer device with 20/20 filter
An inner box containing:
1 single-use 10 ml syringe
1 venous injection set
2 alcohol-soaked swabs
1 non-sterile plaster
A pack with 500 IU/1200 IU or 1000 IU/2400 IU contains:
1 vial with powder
1 vial with 10 ml of water for injections
1 transfer device with 20/20 filter
An inner box containing:
1 single-use 10 ml syringe
1 venous injection set
2 alcohol-soaked swabs
1 non-sterile plaster
Not all pack sizes may be marketed

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Straße 76
35041 Marburg
Germany
For any information relating to the medicine, please contact the local representative of the
Marketing Authorisation Holder

België/Belgique/Belgien
CSL Behring NV
Tél/Tel: +32 15 28 89 20

Lietuva
CentralPharma Communications UAB
Tel: +370 5 243 0444

България
МагнаФарм България
Тел: +359 2 810 3949

Luxembourg/Luxemburg
CSL Behring NV
Tél/Tel: +32 15 28 89 20 (BE)

Magyarország
CSL Behring Kft.
Tel.: +36 1 213 4290

Česká republika
CSL Behring s.r.o.
Tel: + 420 702 137 233

Danmark
CSL Behring AB
Tel: +46 8 544 966 70

Malta
AM Mangion Ltd.
Tel: +356 2397 6333

Deutschland
CSL Behring GmbH
Tel: +49 69 30584437

Nederland
CSL Behring BV
Tel: + 31 85 111 96 00

Eesti
CentralPharma Communications OÜ
Tel: +3726015540

Norge
CSL Behring AB
Tlf: +46 8 544 966 70

Ελλάδα
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

Österreich
CSL Behring GmbH
Tel: +43 1 80101 2463

España
CSL Behring S.A.
Tel: +34 933 67 1870

Polska
CSL Behring sp. z o.o.
Tel: +48 22 213 22 65

France
CSL Behring S.A.
Tél: + 33 –(0)-1 53 58 54 00

Portugal
CSL Behring Lda
Tel: +351 21 782 62 30

Hrvatska
PharmaSwiss d.o.o.
Tel: +385 (1) 631-1833

România
Prisum International Trading srl
Tel: +40 21 322 0171

Ireland
CSL Behring GmbH
Tel: +49 69 30517254

Slovenija
NEOX s.r.o.-podružnica v Sloveniji
Tel:+ 386 41 42 0002

Ísland
CSL Behring AB
Sími: +46 8 544 966 70

Slovenská republika
CSL Behring s.r.o.
Tel: +421 911 653 862

Suomi/Finland
CSL Behring AB
Puh/Tel: +46 8 544 966 70

Italia
CSL Behring S.p.A.
Tel: +39 02 34964 200

Κύπρος
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

Sverige
CSL Behring AB
Tel: +46 8 544 966 70

Latvija
CentralPharma Communications SIA
Tel: +371 6 7450497

United Kingdom (Northern Ireland)
CSL Behring GmbH
Tel: +49 69 30517254 (DE)
Detailed information on this medicine is available on the website of the European Medicines Agency http://www.ema.europa.eu .
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The following information is intended exclusively for healthcare professionals.
Dosage
Von Willebrand disease
It is important to calculate the dose using the number of International Units (IU) of VWF:RCo
specified.
Generally, administration of 1 IU/kg of VWF:RCo results in an increase in circulating VWF:RCo of approximately 0.02 IU/ml (2%).
Levels of VWF:RCo > 0.6 IU/ml (60%) and FVIII:C > 0.4 IU/ml (40%) must be achieved.
On demand
Generally, to achieve haemostasis, administration of 40-80 IU/kg of VWF (VWF:RCo) corresponding to 20-40 IU of FVIII:C/kg body weight is recommended.
Administration of an initial dose of 80 IU/kg of VWF:RCo may be necessary, especially for patients with Type 3 VWF:RCo, in whom maintaining adequate levels of VWF:RCo may require higher doses compared to other types of VWD.
Prevention of bleeding in case of surgery:
To prevent excessive bleeding during or after surgery, administration should begin 1-2 hours before the surgery itself.
An adequate dose should then be repeated every 12-24 hours. The dose to be administered and the duration of treatment depend on the individual clinical situation of the patient, the type and severity of the bleeding, and the levels of VWF:RCo and FVIII:C.
When using VWF-containing preparations also containing FVIII, the physician must bear in mind that prolonged treatment can lead to an excessive increase in FVIII:C levels. To avoid uncontrolled increases in FVIII:C, after 24-48 hours of treatment, it would be appropriate to reduce the dose and/or increase the time interval between administrations, or the use of a VWF product containing a low level of FVIII should be considered.

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

Paediatric population with VWD
Treatment of bleeding
Usually 40-80 IU/kg of von Willebrand factor (VWF:RCo) corresponding to 20-40 IU FVIII:C/kg body weight (BW) are recommended in paediatric patients for the treatment of a haemorrhage.
Prophylactic treatment
Patients aged between 12 and 18 years: Dosage is based on the same guidelines used for adults.
Patients aged <12 years: Based on the results of a clinical study in which paediatric patients under 12 years of age showed lower VWF exposure, a prophylactic dose 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 patient’s clinical condition, as well as their plasma levels of VWF:RCo and FVIII:C.

Haemophilia A
It is important to calculate the dose using the number of IU of FVIII:C specified.
The dose and duration of replacement therapy depend on the severity of the FVIII deficiency, the location and extent of the bleeding, as well as the patient’s clinical condition.
The number of units of factor VIII to be administered is expressed in International Units IU, with reference to the currently valid WHO standard for factor VIII products.
The activity of factor VIII in plasma is expressed either as a percentage (relative to normal human plasma) or preferably in International Units (in accordance with the International Standard for FVIII in plasma).
1 IU of factor VIII activity is equivalent to the amount of factor VIII contained in 1 ml of normal human plasma.

On demand treatment
The calculation of the required dose of factor VIII is based on the empirical finding that 1 IU of factor VIII per kg of body weight increases the activity of factor VIII in plasma by approximately 2% of normal activity (in vivo recovery 2 IU/dl). The required dose is determined using the following formula:
Units required = body weight [kg] x desired increase of factor VIII [% or IU/dl] x 0.5.
The amount and frequency of administrations must always be guided by clinical efficacy in the individual case.
In the case of the following bleeding episodes, the activity of factor VIII should not fall below the activity level indicated (in % normal or in IU/dl) in the corresponding period. The following table can be used as a reference for dosage in the case of bleeding events or surgical interventions:

Monitoring of treatment
During treatment, it is advisable to perform an appropriate determination of factor VIII levels to establish the dose to be administered and the frequency of repeated infusions. Individual patients may show variability in their response to factor VIII, exhibiting different half-lives and recovery levels. Dosage based on body weight may be adjusted in underweight or overweight patients. In particular, in the case of major surgery, careful monitoring of replacement therapy through control of coagulation parameters (plasma factor VIII activity) is essential.

Prophylactic treatment
For long-term prophylaxis in patients with severe haemophilia A, usual doses are 20 to 40 IU of FVIII per kg of body weight at intervals of 2-3 days. In some cases, especially in younger patients, shorter administration intervals or higher doses may be necessary.

Paediatric population in haemophilia A
Dosage in haemophilia A in children and adolescents ˂ 18 years of age is based on body weight and is therefore generally based on the same guidelines used for adults. In some cases, shorter intervals between doses or higher doses may be necessary. The frequency of administration should always be guided by clinical efficacy in the individual case.
Elderly
No dose adjustment is necessary for the elderly population.