InfoCons Consumer Protection informs you – Voncento – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start using this medicine because it contains important information for you .  Keep this leaflet. You may need to read it again.  If you have further questions, ask your doctor, your nurse or your pharmacist.  This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their signs of illness are the s ame as yours.  If you get any side effects talk to your doctor, nurse or pharmacist. This includes any possible side effects not listed in t his leaflet. See section 4.

What is i n this leaflet :

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

ℹ️ 1. What Voncento is and what it is used for

The product is made from human plasma (the liquid part of the blood) and contain s the active substances called huma n coagulation factor VIII (FVIII) and huma n von Willebrand factor (VWF) .

Voncento is used for all age groups to prevent or to haltbleeding caused by the lack of VWF in von Willebrand disease (VWD) and the lack o f FVIII in haemophilia A. Voncento is only used when treatment with another medicine, desmopressin, is not effe ctive alone or cannot be giv en.

VWF and FVIII are involved in blood clotting. Lack of either factor means that blood does not clot as quickly as it sho uld so there is an increased tendency to bleed. The replacement of VWF and FVIII by Voncento will temporarily repair the blood clott ingmechanisms.

As Voncento contains both FVIII and VWF, it is important to know which factor you most need. If you have haemophilia A your doctor will prescribe you Voncento with the number of units of FVIII specified. If you have VWD your doctor will pr escribe you Voncento with the number of units of VWF specified.

⚠️ 2. What you need to know before you use Voncento

Do notuse Voncento 43 If you are allergic to VWF or FVIII or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

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

Talk to your doctor , nurse or pharmacist befor e taking Voncento .  Allergic (hypersensitivity )reactions are possible. If symptoms of hypersensitivity occur, you should stop using th e medicine immediately and contact your doctor. Your doctor should inform you of the early signs of hypersensitivity reactions. Thes e include hives, generalised skin rash, tightness of the chest, wheezing, fall in blood pressure and anaphylaxis (a s erious allergic reaction that causes severe difficulty in breathing, or dizziness).  The formation of inhibitors (antibodies) is a known co mplication that can occur during treatment with all factor VIII medicines. These inhibitors, especially at high level s,stop the treatment working properly and you or your child will be monitored carefully for the development of these inhibitors . If your or your child’s bleeding is not being controlled with Voncento , tell your doctor immediately.  If you have been told y ou have heart disease or are at risk for heart disease, tell your doctor or pharmacist.  If for the administration of Voncento you will requ ire acentral venous access device (CVAD), the risk of CVAD -related complications including local infections, bacteri a in the blood (bacteremia) and the formation of a blood clot in the blood vessel (thrombosis) where the catheter is inserted should be con sidered by your doctor .  von Willebrand disease Ifyou have a known risk of developing blood clots, you must be monit ored fo r early signs of thrombosis (blood clotting) . Your doctor should give you treatment to prevent thrombosis .

Virus safety When medic ines 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 pr ocessing of the blood or plasma that can inactivate or remove viruses.

Despite these measures, when medicines prepared from human b lood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This also applie s to an y 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 cau se 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 seriou s  for pregnant women ( as there is a risk of infection of the unborn child) and 44 for individuals with a weakened immune system or wi th an increased production of red blood cells due to certain types of anaemia (e.g. sickle cell anaemia or haemolytic anaemi a).

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

Children and adolescents

The listed warnings and precautions apply to childre n and adolescents .

Other medicines and Voncento

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

Pregnancy andbreast -feeding  If you are pregnant or breast -feeding, think you may be pregn ant 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 you r abili ty 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 sodium per vial (maincomponent of cooking/table salt) . This is equivalen t to 0.74 % of the recommended maximum daily dietary intake of sodium for an adult .

The presentations 500 IUFVIII /1200 IU VWF (10 ml solvent) and 1000 IU FVIII /2400 IU VWF (10 ml solvent) contain up to 29.50 mg sodium per vial (main component of cooking/table salt) . This is equivalent to 1.48 % of the recommended maximum daily dietary intake of sodium for an adult .

💊 3. How to us e Voncento

Your t reatment should be monitor edby 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 am ount 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 health care pr ofessionals 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.

45Follow 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 sam e instructions as for adults .In some cases, especially in younger patients, higher doses may be needed.

If you use more Voncento than you shoul d Five casesof overdose ha vebeen reported from clinical trials. No sideeffects have been associated with thes ereports . The risk of dev eloping blood clots (thrombosis) cannot be excluded in case of an extremely high dose, especially in patients with VW D.

If you forget to use Voncento

 Proceed with your next dose immediately and continue at regular intervals as advised by your doctor.  Donot take a double dose to make up for a forgotten dose.

If you stop using Voncento

Do not stop using Voncento without co nsulting your doctor .

Reconstitution and application General Instructions  The powder must be mixed with the solvent (liquid) and w ithdrawn from the vial under aseptic conditions.  Voncento must not be mixed with other medicines , diluents or solvent s 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 ch ecked b y 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.

Reconstitu tion Without opening thevials, warm the Voncento powder and the liquid to room or body temperature.

This can be done either by leav ing the vials at room temperature for about an hour, or by holding them in your hands for a few minutes.

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

Carefully remove the protective caps from the vi als, 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.

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

22.Place the solvent vial on an even, clean su rface a nd 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.

33.Carefully remove the blister package from the Mix2Vial set by holding at t he rim, andpulling vertically upwards.

Make sure that you only pull away the blister package and not the Mix2Vial set.

44.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.

55.With one hand grasp the product -side of the Mix2Vial set and with the other hand grasp the solvent -side and unsc rew theset 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.

66.Gently swirl the product vial with the transparent adapter attached u ntil the substance is fully dissolved. Do not shake.

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

Withdrawal and Application 88.While keeping the syringe plunger pressed, turnthe system upside down and draw the solution into the syringe by pulling the plunger back slowly.

99.Now that the solution has been transferred into the syringe, fir mly hold on to the barrel of the syringe (keeping the syringe plunger facing down) and disconnect the transparent Mix2Vial adapter from the syringe by unscr ewing 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 soluti ons of this type. Inject/infuse the reconstituted solution slowly (at a rate not more than 6 ml per minute) into the vein following the ins tructions given to you by your doctor. Take care not to get any blood in the syringe containing the product.

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

Check yourself for any side effects that might happen straight away. If you have any si de effects that might be related to the administration of Voncento , the injection or infusion should be stopped (see also se ction 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 i mmediat elyif:  you notice s ymptoms of allergic reactions In some cases itmay progr ess to a serious allergic reaction (anaphylaxis) that ca uses sever e difficulty in breathing, dizziness or shock. Allergic reactions may include the following symptoms: Swoll en face , tongue, mouth or throat, difficulty in breathing and swallowing, hives, wheezing, burning and stinging where the infusion was give n, chills, flushing, skin rash over the whole body, headache, fall in blood pressure, restlessness, faster heart beat , tight ness of the chest ( including chest pain and chest discomfort), back pain , tiredness (lethargy), nausea, vomiting, tingling.  you notice that the medicine stops working properly (bleeding is not stopped).

For children not previously treated with facto r VIII medicines, inhibitor antibodies (see section 2) may form very commonly (more than 1 in 10 patients); however patients who have recei ved previous treatment with factor VIII (more than 150 days of treatment) the risk is uncommon (less than 1 in 100 pa tients) . If this happens your or your child’s medicines may stop working properly and you or your child may experience persistent bleeding.

You may develop an inhibitor (neutralising antibody) to VWF, in which case VWF will not work properly any more.  you notice any sym ptoms of an impaired perfusion in your extremities (e.g. cold and pale extremities) or vital organs (e.g. severe chestpain) Ther e is a risk of formation of blood clots (thrombosis), particularly in patients with known risk factors (see also section 2).

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

48 Headache The following side effects have been observed commonly (may affect up to 1 in 10 people ):  Increase in body temperature The following si de effectshavebeen observed uncommonly (may affect up to 1 in 100 people ):  Taste alteration (dysgeusia)  Abnormal liver function test Side effects in children and adolescents Side effects in children and adolescents are expecte d to be the same as in a dults.

Reporting of side effects

If you get any side effects, talk to your doctor , nurse or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V . By reporting side effects you can help provide more information on the safety of this medicine.

🌡️ 5. How to store Voncento

 Keep this m edicine out of the sight and reach of children.  Do not use this medicine after the expiry date, which is stated on the label and car ton.  Do not store above 25 °C.  Do not freeze.  Voncento does not contain a preservative, so the reconstitute d produ ct should be used immediately.  If the reconstituted product is not administered immediately, storage times and conditions prior to use are the responsibility of the user .  Keep the vi al in t he outer carton in order to protect from light.  Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment .

📦 6. Contents of t he pack and other information

What Voncento contains

The active substance is:

250 IU FVIII and 600 IU VWF per vial; after reconstitution with 5 ml of water for injection approx.

50 IU/ml FVIII and 120 IU/ml VWF.

500 IU FVIII and 1200 IU VWF per vial; af ter rec onstitution with 10 ml of water for injection approx.

50 IU/ml FVIII and 120 IU/ml VWF.

500 IU FVIII and 1200 IU VWF per vial; after reconstitution with 5 ml of water for injection approx.

100 IU/ml FVIII and 240 IU/ml VWF.

1000 IU FVIII and 2400 IU VWF per vial; after reconstitution with 10 ml of water for injection approx. 100 IU/ml FVIII and 240 IU/ml VWF.

🩺 Information intended for healthcare professionals only

information.

49The other ingredients are:

Calci um chloride, human albumin, sodium chloride, sodium citrate, sucrose, trometamol.

See section 2 “Voncento contains sodium” .

Solvent: Water for injections

What Voncento looks like and contents of the pack

Voncento is supplied as a white powder and solven t for solution for injection /infusion .

The reconstituted solution should be clear to slightly opalescent, i.e. it might sparkle when held up to the light but must not contain any obvious particles.

The imm ediate container of product and solvent via l consi sts of glass vial with a rubber stopper, plastic disc, and aluminium cap.

Presentations One pack with 250 IU/600 IU or 500 IU/1200 IU containing: -1 vial with powder -1 vial with 5 ml water for injection s -1 filter transfer device 20/20 -One inner box containing:

1 disposable 10ml syringe 1 venipuncture set 2 alcohol swabs 1 non -sterile plaster One pack with 500 IU/ 1200 IU or 1000 IU/2400 IU containing: -1 vial with powder -1 vial with 10ml water f or injections -1 filter transfer device 20 /20

• One inner box containing:

1 disposable 10ml syringe 1 venipuncture set 2 alcohol swabs 1 non -sterile plaster Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer CSL Behri ng GmbH Emil-von- Behring -Straße 76 35041 Ma rburg Germany For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien CSL Behring NV Tél/Tel: +32 15 28 89 20Lietuva CentralPharma Communications UAB Tel: +370 5 2 43 0444 България МагнаФарм България Тел: +359 2 810 3949Luxembourg/Luxemburg CSL Behring NV Tél/Tel: +32 15 28 89 20 (BE) 50Česká republika CSL Behring s.r.o.

Tel: + 420 702 137 233Magyarország CSL Behring K ft.

Tel.: +36 1 213 4290 Danmark CSL Behring AB Tel: +46 8 544 966 70Malta AM Mangion Ltd.

Tel: +356 2397 6333 Deutschland CSL Behring GmbH Tel: +49 69 30584437Nede rland 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 Ελλάδ α CSL Behring ΕΠΕ Τηλ: +30 210 7255 660Österreich CSL Behring GmbH Tel: +43 1 80101 2463 España CSL Behring S.A.

Tel: +34 933 67 1870Polska CSL Behring sp. z o.o.

Tel: +48 22 213 22 65 France CSL Behring S.A.

Tél: + 33 –(0)-1 53 58 54 00Port ugal 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 30517254Slovenija NEOX s.r.o. -podružnica v Sloveniji Tel:+ 386 41 42 0002 Ísland CSL Behring AB Sími: +46 8 544 966 70Slovenská republika CSL Behring s .r.o.

Tel: +421 911 653 862 Italia CSL Behring S.p.A.

Tel: +39 02 34964 200Suomi/Finland CSL Behring AB Puh/Te l: +46 8 544 966 70 Κύπρος CSL Behrin g ΕΠΕ Τηλ:+30 210 7255 660Sverige CSL Behring AB Tel: +46 8 544 966 70 Latvija CentralPharma Communications SIA Tel: +371 6 7450497UnitedKingdom ( Northern Ireland ) CSL Behring GmbH Tel: +49 69 30517254 (DE) 51This leaflet was last revised in 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 Willebra nd disease It is impo rtant to calculate the dose using the number of IU of VWF:RCo specified.

Generally, 1 IU/kg VWF:RCo raises th e circu lating 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 achiev ed.

On-demand treatment Usually 40 -80 IU/kg of VWF (VWF:RCo) corresponding to 20 -40 IU FVIII:C/kg of bod y weigh t (BW) are recommended to achieve haemostasis.

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

Prevention of hae morrhage in case of surgery:

For prevention of excessive bleeding during or after surgery the application should start 1 – 2hours befor e the surg ical 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 FVII I:C levels.

When usin g a FVIII -containing VWF product, the treating physician should be aware that continued treatment may cause an excess ive 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.

Prophyla xistreatment For long term prophylaxis in patients with VWD, a dose of 25 -40 IU VWF:RCo /kg body weight should be conside red at a frequency of 1 to 3 times per week. In patients with gastrointestinal bleeds or menorrhagia, shorter dose intervals or higher dose s 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 FVI II: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.

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

52Patients aged <1 2 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.

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

The dose and dur ation o f 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 factor VIII administered is expressed in International Units (IU) , which is related to the current WHO concentrate standard for factor VIII products. Factor VIII activity in plasma is expre ssed either as a perce ntage (relative to normal human plasma) or preferably in International Units (relative to an International Sta ndard f or FVIII in plasma).

1 IU of FVIII activity is equivalent to that quantity of factor VIII in 1 ml of normal human pl asma.

On demand trea tment The calculation of the required dose of factor VIII is based on the empirical finding that 1 IU factor VIII per kg body weight raises the plasma factor VIII activity by about 2 % of normal activity ( in vivo recovery 2 IU/dl). Th e required dose is det ermined using the following formula:

Requir ed units = body weight [kg] x desired factor VIII rise [% or IU/dl ] x 0.5 .

The amount to be administered and the frequency of administration should always be oriented to the clinical effect iveness in the individ ual case.

In the case of the following haemorrhagic events, the factor VIII activity should not fall be low 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:

Degree of haemorrhage / Type of surgical procedureFactor VIII level require d (% or IU/dl)Frequency of doses (hours) / Duration of therapy (days) Haemorrhage Early haemarthrosis, muscle bleeding or oral bleeding20 – 40Repeat infusion every 12 to 24 hours for at least 1 day, until the bleeding episode as indicated by pain is resolved or healing is achieved.

More extensive haemarthrosis, muscle bleeding or haematoma 30 – 60Repeat infusion every 12-24 hours for 3 -4 days or more until pain and acute disability are resolved.

Life-threatening haemorrhages: 60 – 100Repeat in fusion every 8 to 24 hours until threat is resolved.

Surgery Minor surgery including tooth extraction30 – 60Repeat infusion every 24 hours for at least 1 day, until healing is achieved.

Major surgery80 -100 (pre-and postoperative)Repeat infusion every 8 -24 hours until adequate wound healing, then continue therapy for at least another 7 days to maintain a factor VIII activity of 30% -60% (IU/dl) .

53Treatment monitoring During the course of treatment, appropriate determination of factor VIII leve ls is advised to guide the dose to be administered and the frequency of repeated infusions. Individual patients may vary in their response to factor VIII, demonstrating different half -lives and recoveries. Dose based on bodyweight may require adjustment in under weight or overweight patients. In the case of major surgical interventions in particular, a precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable..

Prophylaxis treatment For long ter m prophylaxis in patients with severe haemophilia A, the usual dose is 20 to 40 IU of FVIII per kg body weight at intervals of 2 to 3 days. In some cases, especially in younger patients, shorter dose intervals or higher doses may be necessary.

Paed iatric haemophilia A population Dosing in in haemophilia A in children and adolescents aged ˂18 years is based on body weight and is therefore generally based on the same guidelines as for adults. In some cases shorter dose intervals or higher doses may b e necessary. The frequency of administration should always be oriented to the clinical effec tiveness in the individual case.

Elderly No dose adjustment is necessary for the older people .

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Voncento (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/13/857).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.