Voncento

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
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  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
Voncento 250 IU FVIII / 600 IU VWF powder and solvent for solution for injection/infusion 
One vial of powder contains nominally: 

- 250 IU* human coagulation factor VIII** (FVIII). 
- 600 IU*** human von Willebrand factor** (VWF). 

After reconstitution with the 5 ml water for injections provided, the solution contains 50 IU/ml of 
FVIII and 120 IU/ml of VWF. 
 
Voncento 500 IU FVIII / 1200 IU VWF powder and solvent for solution for injection/infusion 
One vial of powder contains nominally: 

- 500 IU* human coagulation factor VIII** (FVIII). 
- 1200 IU*** human von Willebrand factor** (VWF). 

After reconstitution with the 10 ml water for injections provided, the solution contains 50 IU/ml of 
FVIII and 120 IU/ml of VWF. 
 
Voncento 500 IU FVIII / 1200 IU VWF powder and solvent for solution for injection/infusion 
One vial of powder contains nominally: 

- 500 IU* human coagulation factor VIII** (FVIII). 
- 1200 IU*** human von Willebrand factor** (VWF). 

After reconstitution with the 5 ml water for injections provided, the solution contains 100 IU/ml of 
FVIII and 240 IU/ml of VWF. 
 
Voncento 1000 IU FVIII / 2400 IU VWF powder and solvent for solution for injection/infusion 
One vial of powder contains nominally: 

- 1000 IU* human coagulation factor VIII** (FVIII). 
- 2400 IU*** human von Willebrand factor** (VWF). 

After reconstitution with the 10 ml water for injections provided, the solution contains 100 IU/ml of 
FVIII and 240 IU/ml of VWF. 
_________________________________________ 
* The FVIII potency (IU) is determined using the European Pharmacopoeia chromogenic assay. The 
specific FVIII activity of Voncento, prior to the addition of stabiliser, is approximately 70 IU of 
FVIII/mg protein. 
** produced from plasma of human donors 
***The VWF activity is determined using the WHO Standard for VWF. The specific VWF activity of 
Voncento, prior to the addition of stabiliser, is approximately 100 IU of VWF/mg protein. 



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Excipient with known effect: 
 
Voncento contains approximately 128.2 mmol/l (2.95 mg/ml) of sodium. 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection/infusion. 
White powder and clear, colourless solvent for solution for injection/infusion. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Voncento can be used for all age groups. 
 
von Willebrand disease (VWD) 
 
Prophylaxis and treatment of haemorrhage or surgical bleeding in patients with VWD, when 
desmopressin (DDAVP) treatment alone is ineffective or contraindicated.  
 
Haemophilia A (congenital FVIII deficiency) 
 
Prophylaxis and treatment of bleeding in patients with haemophilia A. 
 
 
4.2 Posology and method of administration 
 
Treatment of VWD and haemophilia A should be supervised by a physician experienced in the 
treatment of haemostatic disorders. 
 
The decision on the use of the product at home for patients with VWD and with haemophilia A should 
be made by the treating physician who should ensure that appropriate training is provided and the use 
is reviewed at intervals. 
 
The ratio between FVIII:C and VWF:RCo in a vial is approximately 1:2.4. 
 
Treatment monitoring 
During the course of treatment, appropriate determination of factor VIII levels 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 underweight or overweight patients. In the case of major surgical 
interventions in particular, precise monitoring of the substitution therapy by means of coagulation 
analysis (plasma factor VIII activity) is indispensable. 
 
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. 
 



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On-demand treatment 
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 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 (see section 5.2).  
 
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. (see Section 5.2). 
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 factor VIII 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 expressed either as a percentage (relative to normal human plasma) or preferably in 
International Units (relative to an International Standard for factor VIII in plasma). 
 
1 IU of factorVIII activity is equivalent to that quantity of factor VIII in 1 ml of normal human 
plasma.  
 
On demand treatment 



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The calculation of the required dose of factor VIII is based on the empirical finding that 
1 International Unit (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). The required dose is determined using the following 
formula: 
 
Required 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 effectiveness in the individual case.  
In the case of the following haemorrhagic events, the factor VIII 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: 
 
Degree of haemorrhage / Type 
of surgical procedure 

Factor VIII level 
required (% or IU/dl) 

Frequency of doses (hours) / 
Duration of therapy (days) 

Haemorrhage   

Early haemarthrosis, muscle 
bleeding or oral bleeding 20 - 40 

Repeat infusion every 12 - 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 - 60 

Repeat infusion every 12 - 24 hours for 
3 - 4 days or more until pain and acute 
disability are resolved. 

Life-threatening haemorrhages 60 - 100 Repeat infusion every 8 - 24 hours until threat is resolved. 
Surgery   
Minor surgery 
including tooth extraction 30 - 60 

Repeat infusion every 24 hours for at 
least 1 day, until healing is achieved. 

Major surgery 80 - 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). 

 
Prophylaxis treatment 
For long term prophylaxis in patients with severe haemophilia A, the usual dose is 20 to 40 IU of 
factor VIII 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. 
 
Paediatric haemophilia A population 
Dosing in haemophilia A in children and adolescents aged ˂ 18 years old 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 be necessary. The frequency of administration should always be oriented to the 
clinical effectiveness in the individual case. 
 
Currently available data are described in Sections 4.8and 5.2. 
 
Elderly 
No dose adjustment is necessary for the older people. 
 
Method of administration 
 
For intravenous use. 
For instructions on reconstitution of the medicinal product before administration, see section 6.6. The 
reconstituted preparation should be injected/infused slowly intravenously at a rate comfortable for the 
patient.  



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The injection/infusion rate should not exceed 6 ml per minute. The patient should be observed for any 
immediate reaction. If any reaction takes place that might be related to the administration of Voncento, 
the rate of injection should be decreased or the application should be stopped, as required by the 
clinical condition of the patient (see also section 4.4). 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
It is strongly recommended that every time that Voncento is administered to a patient, the name and 
batch number of the product are recorded in order to maintain a link between the patient and the batch 
of the product. 
 
Hypersensitivity 
 
Allergic type hypersensitivity reactions are possible. If symptoms of hypersensitivity occur, patients 
should be advised to discontinue use of the medicinal product immediately and contact their physician. 
Patients should be informed of the early signs of hypersensitivity reactions including hives, 
generalised urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis. In case of shock, 
the current medical standards for shock treatment should be observed.  
 
Virus safety 
 
Standard measures to prevent infections resulting from the use of medicinal products prepared from 
human blood or plasma include selection of donors, screening of individual donations and plasma 
pools for specific markers of infection and the inclusion of effective manufacturing steps for the 
inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or 
plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. 
This also applies to unknown or emerging viruses and other pathogens.  
 
The measures taken are considered effective for enveloped viruses such as human immunodeficiency 
virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and for the non-enveloped hepatitis 
A virus (HAV). 
 
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 (foetal infection) and for individuals 
with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia). 
 
Appropriate vaccination (hepatitis A and B) should be considered for patients in regular/repeated 
receipt of human plasma-derived factor VIII/VWF products. 
 
von Willebrand disease 
 
There is a risk of occurrence of thrombotic events, particularly in patients with known clinical or 
laboratory risk factors. Therefore, patients at risk must be monitored for early signs of thrombosis. 
Prophylaxis against venous thromboembolism should be instituted, according to the current 
recommendations. 
 
When using a FVIII-containing VWF product, the treating physician should be aware that continued 
treatment may cause an excessive rise in FVIII:C. In patients receiving FVIII-containing VWF 
products, plasma levels of FVIII:C should be monitored to avoid sustained excessive FVIII:C plasma 



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levels which may increase the risk of thrombotic events, and antithrombotic measures should be 
considered (see also section 5.2). 
 
Patients with VWD, especially type 3 patients, may develop neutralising antibodies (inhibitors) to 
VWF. If the expected VWF:RCo activity plasma levels are not attained, or if bleeding is not controlled 
with an appropriate dose, an appropriate assay should be performed to determine if a VWF inhibitor is 
present. In patients with high levels of inhibitor, therapy may not only be ineffective but also lead to 
anaphylactoid reactions and other therapeutic options should be considered.  
 
Haemophilia A 
 
Inhibitors 
The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in the 
management of individuals with haemophilia A. These inhibitors are usually IgG immunoglobulins 
directed against the factor VIII procoagulant activity, which are quantified in Bethesda Units (BU) per 
ml of plasma, using the modified assay. The risk of developing inhibitors is correlated to the severity 
of the disease as well as exposure to factor VIII, this risk being highest within the first 50 exposure 
days but continues throughout life although the risk is uncommon.  
 
The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titre 
posing less of a risk of insufficient clinical response than high titre inhibitors. 
In general, all patients treated with coagulation factor VIII products should be carefully monitored for 
the development of inhibitors by appropriate clinical observations and laboratory tests. If the expected 
factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate 
dose, testing for FVIII inhibitor presence should be performed. In patients with high levels of 
inhibitor, factor VIII therapy may not be effective and other therapeutic options should be considered. 
Management of such patients should be directed by physicians with experience in the care of 
haemophilia and factor VIII inhibitors. 
 
Cardiovascular events  
In patients with existing cardiovascular risk factors, substitution therapy with FVIII may increase the 
cardiovascular risk. 
 
Catheter-related complications 
 
If a central venous access device (CVAD) is required, risk of CVAD-related complications including 
local infections, bacteremia and catheter site thrombosis should be considered. 
 
Sodium content 
 
Presentations with 250 IU FVIII / 600 IU VWF (5 ml solvent) and 500 IU FVIII / 1200 VWF IU (5 ml 
solvent): contain up to 14.75 mg (0.64 mmol) sodium per vial, equivalent to 0.74% of the WHO 
recommended maximum daily intake of 2 g sodium for an adult. 
 
Presentations with 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, equivalent to 1.48% of the 
WHO recommended maximum daily intake of 2 g sodium for an adult. 
 
Paediatric population 
 
The listed warnings and precautions apply both to adults and paediatrics. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction of VWF and FVIII with other medicinal products have been studied. 
 



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4.6 Fertility, pregnancy and lactation 
 
Animal reproduction studies have not been conducted with Voncento. 
 
von Willebrand disease 
 
Experience in the treatment of pregnant or breast-feeding women is not available. Voncento should be 
administered to pregnant or breast-feeding VWF deficient women only if clearly indicated, taking into 
consideration that delivery confers an increased risk of haemorrhagic events in these patients. 
 
Haemophilia A 
 
Based on the rare occurrence of haemophilia A in women, experience regarding the treatment during 
pregnancy and breastfeeding is not available.  
Therefore, Voncento should be used during pregnancy and breast-feeding only if clearly indicated. 
 
Fertility 
 
There are no data on fertility available. 
 
4.7 Effects on ability to drive and use machines 
 
Voncento has no influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
During treatment with Voncento the following adverse reactions may occur:  
Hypersensitivity or allergic reactions, thromboembolic events, pyrexia, headache, dysgeusia and 
abnormal liver function test levels. Furthermore patients may develop inhibitors to FVIII and VWF. 
 
Tabulated list of adverse reactions  
 
The table presented below is according to the MedDRA system organ classification.  
 
Frequencies have been evaluated according to the following convention: very common (≥1/10); 
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare 
(<1/10,000), not known (cannot be estimated from the available data).  



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Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
MedDRA Standard System 
Organ Class  

Adverse Reaction*  Frequency 

Blood and lymphatic system 
disorders 

FVIII inhibition  
 
 
VWF inhibition 

Uncommon (PTPs)** 
Very common (PUPs)** 
 
Not known*** 

Immune system disorders Hypersensitivity (including 
tachycardia, chest pain, chest 
discomfort and back pain) 

Common 

Nervous system disorders Dysgeusia Uncommon 
Vascular disorders Thromboembolic event Uncommon 
General disorders and 
administration site conditions 

Pyrexia 
Headache 

Common  
Very common 

Investigations Liver function test abnormal Uncommon 
* Adverse events assessed as related to administration of the Voncento 
**Frequency is based on studies with all FVIII products which included patients with severe 
haemophilia A. PTPs = previously-treated patients, PUPs = previously-untreated patients. 
*** Observed during postmarketing surveillance, not observed in clinical trials. 
 
Description of selected adverse reactions 
 
Hypersensitivity (allergic reactions) 
Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the 
infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, 
restlessness, tachycardia, tightness of the chest (including chest pain and chest discomfort), back pain, 
tingling, vomiting, wheezing) have been observed, and may in some cases progress to severe 
anaphylaxis (including shock). 
 
FVIII inhibition 
Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated 
with factor VIII, including with Voncento. If such inhibitors occur, the condition may manifest itself 
as an insufficient clinical response. In such cases, it is recommended that a specialised haemophilia 
centre be contacted.  
 
VWF inhibition 
Patients with VWD, especially type 3 patients, may develop neutralising antibodies (inhibitors) to 
VWF. If such inhibitors occur, the condition will manifest itself as an inadequate clinical response. 
Such antibodies are precipitating and may occur concomitantly to anaphylactic reactions. Therefore, 
patients experiencing an anaphylactic reaction should be evaluated for the presence of an inhibitor. In 
all such cases, it is recommended that a specialised haemophilia centre be contacted.  
 
Thromboembolic events 
In patients with VWD, there is a risk of occurrence of thromboembolic events, particularly in patients 
with known clinical or laboratory risk factors. In patients receiving FVIII-containing VWF products, 
sustained excessive FVIII:C plasma levels may increase the risk of thromboembolic events (see also 
section 4.4). 
 
For safety with respect to transmissible agents, see section 4.4.  
 
Paediatric population  
 
Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. 



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Reporting of suspected adverse reactions  
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Five cases of overdose have been reported from clinical trials. No adverse reactions have been 
associated with these reports. 
 
The risk of thromboembolic events cannot be excluded in case of major overdose, especially in 
patients with VWD. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: antihaemorrhagics,blood coagulation factors, von Willebrand factor and 
coagulation factor VIII in combination, ATC code: B02BD06 
 
von Willebrand disease 
 
Exogenously administered human plasma-derived VWF behaves in the same way as endogenous 
VWF. 
 
Administration of VWF allows correction of the haemostatic abnormalities exhibited by patients who 
suffer from VWF deficiency (VWD) at two levels: 
- VWF re-establishes platelet adhesion to the vascular sub-endothelium at the site of vascular 

damage (as it binds both to the vascular sub-endothelium and to the platelet membrane), 
providing primary haemostasis as shown by the shortening of the bleeding time. This effect 
occurs immediately and is known to depend to a large extent on the level of polymerisation of 
the protein. 

- VWF produces delayed correction of the associated FVIII deficiency. Administered 
intravenously, VWF binds to endogenous FVIII (which is produced normally by the patient), 
and by stabilising this factor, avoids its rapid degradation. 
Because of this, administration of pure VWF (VWF product with a low FVIII level) restores the 
FVIII:C level to normal as a secondary effect after the first infusion with a slight delay. 

- Administration of a FVIII:C containing VWF preparation restores the FVIII:C level to normal 
immediately after the first infusion. 

 
Haemophilia A 
 
Exogenously administered human plasma-derived FVIII behaves in the same way as endogenous 
FVIII. 
 
The FVIII/VWF complex consists of two molecules (FVIII and VWF) with different physiological 
functions.  When infused into a haemophiliac patient, FVIII binds to VWF in the patient’s circulation. 
Activated FVIII acts as a cofactor for activated factor IX accelerating the conversion of factor X to 
activated factor X. Activated factor X converts prothrombin into thrombin. Thrombin then converts 
fibrinogen into fibrin and a clot can be formed. Haemophilia A is a sex-linked hereditary disorder of 
blood coagulation due to decreased levels of FVIII and results in profuse bleeding into joints, muscles 
or internal organs, either spontaneously or as a result of accidental or surgical trauma. By replacement 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


11 

therapy the plasma level of FVIII is increased, thereby enabling a temporary correction of the factor 
deficiency and correction of the bleeding tendency. 
 
Of note, annualized bleeding rate (ABR) is not comparable between different factor concentrates and 
between different clinical studies. 
 
5.2 Pharmacokinetic properties 
 
von Willebrand disease 
 
The pharmacokinetics of Voncento have been evaluated in VWD patients in the non-bleeding state.  
 
Based on a pharmacokinetic study with 12 subjects ≥12 years with VWD, the following 
pharmacokinetic characteristics for VWF:RCo, VWF:Ag, VWF:CB and FVIII:C were observed: 
 
 VWF:RCo VWF:Ag VWF:CB FVIII:C 
parameter N median range N median range N median range N median range 
Incremental  
recovery 
(IU/mL)/(IU/kg) 

12 0.017 0.012-0.021 12 0.018 0.013-0.022 12 0.022 0.015-0.025 12 0.027 0.016-0.036 

Half-life (h) 8 11.53 6.05-35.10 12 18.39 11.41-27.01 12 14.54 9.36-25.10 10 23.65 7.69-57.48 
AUC0-72 
(h*IU/mL) 12 14.46 8.56-37.99 12 33.10 22.65-64.68 12 24.32 14.83-41.14 11 27.85 13.15-66.82 

MRT (h) 8 13.25 8.59-25.45 12 24.57 15.28-33.60 12 18.74 11.61-28.57 10 36.57 15.62-85.14 
Cmax (IU/mL) 12 1.48 0.93-3.36 12 2.04 1.52-3.66 12 1.60 1.04-2.66 12 1.00 0.57-1.32 
Tmax (h) 12 0.25 0.25-1.03 12 0.25 0.25-1.00 12 0.25 0.25-1.00 12 1.00 0.25-30.00 
Cmin (IU/mL) 12 0.02 0.00-0.03 12 0.10 0.02-0.17 12 0.05 0.02-0.09 12 0.14 0.03-0.59 
Total clearance 
(mL/(h*kg)) 12 6.16 3.06-9.32 12 3.74 2.61-4.78 12 3.20 2.32-4.77 11 1.28 0.62-2.47 

Vss (ml/kg) 8 68.3 44.7-158.0 12 74.0 64.5-128.4 12 71.0 47.5-93.7 10 47.5 24.8-72.9 
AUC = area under the curve; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; IU = 
International Unit; MRT = mean residence time; N = number of subjects;tmax = time to maximum concentration; Vss = 
volume of distribution at steady state; VWF:Ag = von Willebrand factor: Antigen; VWF:CB = von Willebrand factor: 
Collagen Binding; VWF:RCo = von Willebrand factor: Ristocetin Cofactor, FVIII:C = Factor VIII: Coagulant 
 
The relative content of HMW (high molecular weight) VWF multimers in Voncento is on average 86 
% when compared to normal human plasma (NHP).  
 
Haemophilia A 
The pharmacokinetics of Voncento have been evaluated in haemophilia A patients in the non-bleeding 
state.  
 
Based on a pharmacokinetic study with 16 subjects ≥ 12 years of age with haemophilia A, the 
following pharmacokinetic characteristics for FVIII:C were observed: 
 
 FVIII:C 
parameter N median range 
Incremental recovery (IU/mL)/(IU/kg) 16 0.021 0.011-0.032 
Half-life (h) 16 13.74 8.78-18.51 
AUC0-48(h*IU/mL) 16 13.09 7.04-21.79 
MRT (h) 16 16.62 11.29-26.31 
Cmax (IU/mL) 16 1.07 0.57-1.57 
Tmax (h) 16 0.50 0.42-4.03 
Cmin (IU/mL) 16 0.06 0.02-0.11 
Total clearance(mL/(h*kg) 16 3.82 2.30-7.11 
Vss (ml/kg) 16 61.2 35.1-113.1 
AUC = area under the curve; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; IU = 
International Unit; MRT = mean residence time; N = number of subjects; tmax = time to maximum concentration; Vss = 
volume of distribution at steady state; FVIII:C = Factor VIII: Coagulant 
 
Paediatric population 
 



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von Willebrand disease 
 
The pharmacokinetic data in patients with von Willebrand disease are very similar to those observed 
in the adult population. 
 
PK of single dose of 80 IU VWF:RCo/kg body weight was evaluated in paediatric subjects less than 
12 years of age with severe VWD (see Table below). Following infusion, peak concentrations of VWF 
markers (VWF:RCo, VWF:Ag, and VWF:CB) and FVIII:C were achieved immediately with a median 
IR of 0.012-0.016 (IU/mL)/(IU/kg) for VWF markers and 0.018-0.020 (IU/mL)/(IU/kg) for FVIII:C. 
The median elimination t1/2 of VWF markers was between 10.00 and 13.48 h whereas FVIII:C had a 
longer t1/2 between 11.40 and 19.54 h due to a plateau effect that may represent the net effect of 
decreasing levels of exogenous FVIII, combined with increasing endogenous FVIII levels. PK 
parameters from the repeat PK evaluation were similar to those from initial PK. Voncento exposure 
and disposition were comparable between <6-year-old and 6-12-year-old subjects. 
 
Baseline-adjusted initial PK parameters of VWF and FVIII:C in subjects <6 (N=9) and 6-12 years old 
(N=5) 
 VWF:RCo VWF:Ag VWF:CB FVIII:C 

parameter N 
median 
(range) 

N 
median 
(range) 

N 
median 
(range) 

N 
median 
(range) 

N 
median 
(range) 

N 
median 
(range) 

N 
median 
(range) 

N 
median 
(range) 

 <6 years 6-12 years <6 years 6-12 years <6 years 6-12 years <6 years 6-12 years 
Incremental  
recovery  
(IU/mL)/(IU/kg) 

9 
0.012 

(0.009-
0.017) 

5 
0.016 

(0.009-
0.017) 

9 
0.014 

(0.007-
0.016) 

5 
0.015 

(0.014-
0.022) 

9 
0.014 

(0.009-
0.017) 

5 
0.014 

(0.010-
0.016) 

8 
0.018 

(0.012-
0.048) 

5 
0.020 

(0.008-
0.026) 

Half-life  
(h) 

5 
13.48 
(4.13-
22.44) 

3 
11.20 
(8.55-
11.59) 

8 
11.15 
(7.72-
22.36) 

5 
11.00 
(8.61-
12.14) 

8 
10.53 
(6.08-
15.44) 

5 
10.00 
(7.20-
12.11) 

4 
19.54 

(17.96-
20.70) 

3 
11.40 
(7.05-
32.61) 

AUC0-72 
(h*IU/mL) 

9 
7.40 

(4.26-
17.71) 

5 
10.44 
(3.11-
15.85) 

9 
19.41 

(11.71-
34.55) 

5 
21.75 

(18.72-
27.77) 

9 
15.49 

(11.10-
25.30) 

5 
16.46 

(12.84-
19.63) 

8 
15.45 
(8.25-
32.36) 

5 
19.81 
(1.47-
34.82) 

MRT  
(h) 

5 
16.68 
(4.36-
32.74) 

3 
12.99 
(8.48-
13.03) 

8 
13.31 
(9.03-
31.68) 

5 
13.26 

(11.06-
15.72) 

8 
12.87 
(7.17-
20.96) 

5 
11.70 
(9.19-
15.22) 

4 
25.78 

(23.87-
28.42) 

3 
15.92 
(6.63-
44.40) 

Cmax  
(IU/mL) 

9 
1.06 

(0.69-
1.35) 

5 
1.30 

(0.71-
1.34) 

9 
1.66 

(1.22-
1.92) 

5 
1.79 

(1.44-
2.50) 

9 
1.44 

(1.13-
1.93) 

5 
1.28 

(1.23-
1.83) 

8 
0.71 

(0.46-
1.46) 

5 
0.57 

(0.33-
0.96) 

Tmax  
(h) 

9 
0.55 

(0.50-
0.62) 

5 
0.58 

(0.50-
0.60) 

9 
0.55 

(0.50-
0.62) 

5 
0.58 

(0.50-
0.60) 

9 
0.55 

(0.50-
0.62) 

5 
0.58 

(0.50-
0.60) 

8 
0.58 

(0.50-
22.52) 

5 
0.58 

(0.50-
0.60) 

Total clearance 
(mL/(h*kg) 

5 
7.30 

(2.82-
17.32) 

3 
7.22 

(6.14-
8.62) 

8 
5.63 

(2.24-
13.13) 

5 
4.93 

(4.48-
5.10) 

8 
7.03 

(3.66-
11.74) 

5 
6.22 

(5.25-
7.14) 

4 
2.46 

(1.29-
3.87) 

3 
4.81 

(0.96-
26.07) 

Vss  
(ml/kg) 

5 
112.1 
(52.3-
135.3) 

3 
80.1 

(73.1-
93.8) 

8 
76.8 

(70.3-
133.5) 

5 
67.5 

(54.6-
70.4) 

8 
84.4 

(67.1-
113.8) 

5 
79.7 

(54.7-
95.9) 

4 
67.5 

(33.1-
92.5) 

3 
76.6 

(42.6-
172.9) 

AUC = area under the curve; Cmax = maximum plasma concentration; IU = International Unit; MRT = mean residence time; 
N = number of subjects; tmax = time to maximum concentration occurs; Vss = volume of distribution at steady state; VWF:Ag 
= von Willebrand factor: Antigen; VWF:CB = von Willebrand factor: Collagen Binding; VWF:RCo = von Willebrand factor: 
Ristocetin Cofactor, FVIII:C = Factor VIII: Coagulant 
 
Haemophilia A 
 
PK of single dose of 50 IU FVIII/kg body weight was evaluated in 31 paediatric subjects less than 12 
years of age with Haemophilia A (see Table below). Following infusion, peak concentrations of 
FVIII:C were achieved immediately with a median IR of approximately 0.016 (IU/mL)/(IU/kg) for 
FVIII:C. The median elimination t1/2 of FVIII:C was approximately 10 h. PK parameters from the 
repeat PK evaluation were similar to those from initial PK. Voncento exposure and disposition were 
comparable between <6-year-old and 6-12-year-old subjects. 
 



13 

Baseline-adjusted initial PK parameters of FVIII:C in subjects <6 (N=15) and 6-12 years old (N=16) 
 FVIII:C 
parameter N median range N median range 
 <6 years 6-12 years 
Incremental recovery (IU/mL)/(IU/kg) 15 0.015 0.009-0.019 16 0.016 0.010-0.026 
Half-life (h) 15 9.62 7.75-18.20 16 10.00 8.89-12.50 
AUC0-48 (h*IU/mL) 15 8.23 3.96-11.04 16 9.90 6.17-17.62 
MRT (h) 15 13.51 7.95-17.38 16 13.89 12.11-17.07 
Cmax (IU/mL) 15 0.75 0.46-0.94 16 0.84 0.51-1.21 
Tmax (h) 15 0.58 0.53-0.58 16 0.58 0.50-1.00 
Total clearance (mL/(h*kg) 15 6.22 4.22-11.34 16 4.88 2.54-7.74 
Vss (ml/kg) 15 75.3 63.8-197.2 16 71.9 42.1-109.3 
AUC = area under the curve; Cmax = maximum plasma concentration; Cmin = minimum plasma concentration; IU = 
International Unit; MRT = mean residence time; N = number of subjects; tmax = time to maximum concentration; Vss = 
volume of distribution at steady state; FVIII:C = Factor VIII: Coagulant 
 
5.3 Preclinical safety data 
 
Voncento contains FVIII and VWF as active ingredients which are derived from human plasma and 
act like endogenous constituents of plasma. Preclinical studies with repeated dose applications 
(chronic toxicity, carcinogenicity and mutagenicity) cannot be reasonably performed in conventional 
animal models due to the development of antibodies following the application of heterologous human 
proteins. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder 
Calcium chloride 
Human albumin 
Sodium chloride 
Sodium citrate 
Sucrose 
Trometamol 
 
Solvent 
Water for injections  
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products, diluents or solvents except those mentioned in section 6.1. 
 
6.3 Shelf life 
 
3 years. 
 
After reconstitution the chemical and physical in-use stability has been demonstrated for 8 hours at 
room temperature (below 25 °C). From a microbiological point of view, the product should be used 
immediately. If not used immediately, in-use storage times and conditions prior to use are the 
responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C.  
 
6.4 Special precautions for storage 
 
Do not store above 25 °C.  



14 

 
Do not freeze. Keep vials in the outer carton in order to protect from light. 
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Voncento 250 IU FVIII / 600 IU VWF powder and solvent for solution for injection/infusion 
Powder (250 IU/600 IU) in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap 
(aluminium).  
5 ml of solvent in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap 
(aluminium). 
 
One pack contains: 
1 vial with powder 
1 vial with 5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe 
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
Voncento 500 IU FVIII / 1200 IU VWF powder and solvent for solution for injection/infusion 
Powder (500 IU/1200 IU) in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap 
(aluminium).  
10 ml of solvent in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap (aluminium). 
 
One pack contains: 
1 vial with powder 
1 vial with 10 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe 
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
Voncento 500 IU FVIII / 1200 IU VWF powder and solvent for solution for injection/infusion 
Powder (500 IU/1200 IU) in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap 
(aluminium).  
5 ml of solvent in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap (aluminium). 
 
One pack contains: 
1 vial with powder 
1 vial with 5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe 
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
Voncento 1000 IU FVIII / 2400 IU VWF powder and solvent for solution for injection/infusion 
Powder (1000 IU/2400 IU) in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap 
(aluminium).  



15 

10 ml of solvent in a vial (type I glass) with a stopper (rubber) a disc (plastic) and a cap (aluminium). 
 
One pack contains: 
1 vial with powder 
1 vial with 10 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe 
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
General instructions 
 
The solution should be clear or slightly opalescent. After filtering/withdrawal (see below) the 
reconstituted product should be inspected visually for particulate matter and discoloration prior to 
administration. Do not use visibly cloudy solutions or solutions still containing flakes or particles.  
Reconstitution and withdrawal must be carried out under aseptic conditions. 
 
Reconstitution 
 
Bring the solvent to room temperature. Ensure powder and solvent vial flip caps are removed and the 
stoppers are treated with an antiseptic solution and allowed to dry prior to opening the Mix2Vial 
package. 
 

 1 

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

 2 

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 

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 

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. 



16 

 5 

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 

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

 7 

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 

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 

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. 

 
For injection of Voncento only the provided administration sets should be used because treatment 
failure can occur as a consequence of FVIII adsorption to the internal surfaces of some 
injection/infusion equipment. 
 
In case large volumes of Voncento are required, it is possible to pool several vials of Voncento via a 
commercially available infusion set (e.g. a syringe pump for intravenous application of medicinal 
products). However, in these cases the initially reconstituted solution of Voncento should not be 
diluted any further. 
 
Administer the solution slowly intravenously (see section 4.2), taking care to ensure that no blood 
enters the syringe filled with product.  



17 

 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH 
Emil-von-Behring-Str. 76 
35041 Marburg 
Germany 
 
 
8. MARKETING AUTHORIZATION NUMBER(S) 
 
EU/1/13/857/001 
EU/1/13/857/002 
EU/1/13/857/003 
EU/1/13/857/004 
 
 
9. DATE OF FIRST AUTHORIZATION/RENEWAL OF THE AUTHORIZATION 
 
Date of first authorisation: 12 August 2013 
Date of latest renewal: 26 April 2018 
 
10. DATE OF REVISION OF THE TEXT 
 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
 

http://www.ema.europa.eu/


18 

 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

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

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



19 

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

 
Name and address of the manufacturer(s) of the biological active substances  
 
CSL Behring AG 
Wankdorfstrasse 10 
3014 Bern 
SWITZERLAND 
 
CSL Behring (Australia) Pty Ltd  
189-209 Camp Road 
Broadmeadows 
Victoria 3047 
AUSTRALIA 
 
Name and address of the manufacturer(s) responsible for batch release 
CSL Behring GmbH 
Emil-von-Behring-Straße 76 
35041 Marburg 
GERMANY 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
• Official batch release  
 
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. 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic safety update reports  
 
The marketing authorisation holder shall submit the first periodic safety update report for this 
product within six months following authorisation. Subsequently, the marketing authorisation holder 
shall submit periodic safety update reports for this product in accordance with the requirements set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and 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; 



20 

• 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.  

 
If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 
time. 
 



21 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



22 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



23 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
Carton 250 IU/600 IU 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Voncento 250 IU FVIII / 600 IU VWF (5 ml solvent) powder and solvent for solution for 
injection/infusion 
human coagulation factor VIII/human von Willebrand factor 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
human coagulation factor VIII 250 IU  
human von Willebrand factor 600 IU 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: calcium chloride, human albumin, sodium chloride, sodium citrate, sucrose, 
trometamol. See leaflet for further information. 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection/infusion 
1 vial with powder  
1 vial with 5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 

OUT OF THE SIGHT AND REACH OF CHILDREN 
 
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 below 25 °C. Do not freeze.  
Keep the vials in the outer carton in order to protect from light. 



24 

 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/857/001 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Voncento 250 IU / 600 IU 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



25 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Powder vial 250 IU/600 IU 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Voncento 250 IU FVIII / 600 IU VWF powder for solution for injection/infusion 
For IV use 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
coagulation factor VIII 250 IU  
von Willebrand factor 600 IU 
 
6. OTHER 
 
 



26 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Solvent vial label 5 ml 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Water for injections 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
 
6. OTHER 
 



27 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
Carton 500 IU/1200 IU 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Voncento 500 IU FVIII / 1200 IU VWF(10 ml solvent) powder and solvent for solution for 
injection/infusion 
human coagulation factor VIII/human von Willebrand factor 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
human coagulation factor VIII 500 IU  
human von Willebrand factor 1200 IU 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: calcium chloride, human albumin, sodium chloride, sodium citrate, sucrose, 
trometamol. See leaflet for further information. 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection/infusion 
1 vial with powder  
1 vial with 10 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use  
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 

OUT OF THE SIGHT AND REACH OF CHILDREN 
 
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 below 25 °C. Do not freeze.  



28 

Keep the vials in the outer carton in order to protect from light. 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/857/002 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Voncento 500 IU / 1200 IU 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 



29 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
Powder vial 500 IU/1200 IU 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Voncento 500 IU FVIII /1200 IU VWF powder for solution for injection/infusion 
For IV use 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
coagulation factor VIII 500 IU  
von Willebrand factor 1200 IU 
 
6. OTHER 
 
 



30 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Solvent vial label 10 ml 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Water for injections 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 ml 
 
6. OTHER 
 
 
 



31 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
Carton 500 IU/1200 IU 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Voncento 500 IU FVIII / 1200 IU VWF (5 ml solvent) powder and solvent for solution for 
injection/infusionhuman coagulation factor VIII/human von Willebrand factor 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
human coagulation factor VIII 500 IU  
human von Willebrand factor 1200 IU 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: calcium chloride, human albumin, sodium chloride, sodium citrate, sucrose, 
trometamol. See leaflet for further information. 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection/infusion 
1 vial with powder  
1 vial with 5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 

OUT OF THE SIGHT AND REACH OF CHILDREN 
 
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 below 25 °C. Do not freeze.  
Keep the vials in the outer carton in order to protect from light. 
 



32 

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

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/857/003 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Voncento 500 IU / 1200 IU 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



33 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Powder vial 500 IU/1200 IU 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Voncento 500 IU FVIII / 1200 IU VWF powder for solution for injection/infusion 
For IV use 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
coagulation factor VIII 500 IU  
von Willebrand factor 1200 IU 
 
6. OTHER 
 
 
 



34 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Solvent vial label 5 ml 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Water for injections 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
 
6. OTHER 
 
 
 



35 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
Carton 1000 IU/2400 IU 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Voncento 1000 IU FVIII / 2400 IU VWF (10 ml solvent) powder and solvent for solution for 
injection/infusionhuman coagulation factor VIII/human von Willebrand factor 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
human coagulation factor VIII 1000 IU  
human von Willebrand factor 2400 IU 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: calcium chloride, human albumin, sodium chloride, sodium citrate, sucrose, 
trometamol. See leaflet for further information. 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection/infusion 
1 vial with powder  
1 vial with 10 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED 

OUT OF THE SIGHT AND REACH OF CHILDREN 
 
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 below 25 °C. Do not freeze.  
Keep the vials in the outer carton in order to protect from light. 
 



36 

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

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/13/857/004 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Voncento 1000 IU / 2400 IU 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: SN: 
NN: 
 



37 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Powder vial 1000 IU/2400 IU 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Voncento 1000 IU FVIII / 2400 IU VWF powder for solution for injection/infusion 
ForIV use 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
coagulation factor VIII 1000 IU  
von Willebrand factor 2400 IU 
 
6. OTHER 
 
 



38 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Solvent vial label 10 ml 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Water for injections 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
10 ml 
 
6. OTHER 
 
 



39 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
Carton administration set (inner box) 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Administration set 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
-not applicable- 
 
3. LIST OF EXCIPIENTS 
 
-not applicable- 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
-not applicable- 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
-not applicable- 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE REACH AND SIGHT OF CHILDREN 
 
-not applicable- 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
-not applicable- 
 
8. EXPIRY DATE 
 
Exp. date 
 
9. SPECIAL STORAGE CONDITIONS 
 
-not applicable- 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 

WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
-not applicable- 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
-not applicable- 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
-not applicable- 
 
13. BATCH NUMBER 



40 

 
Lot No. 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
-not applicable- 
 
15. INSTRUCTIONS ON USE 
 
-not applicable- 
 
16. INFORMATION IN BRAILLE 
 
-not applicable- 
 



41 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



42 

 
 

 
Package Leaflet: Information for the user 

 
 

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 

 
 
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 same as yours. 
• If you get any side effects talk to your doctor, nurse or pharmacist. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in 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 
 
 
1. What Voncento is and what it is used for  
 
The product is made from human plasma (the liquid part of the blood) and contains the active 
substances called human coagulation factor VIII (FVIII) and human von Willebrand factor (VWF).  
 
Voncento is used for all age groups to prevent or to halt bleeding caused by the lack of VWF in von 
Willebrand disease (VWD) and the lack of FVIII in haemophilia A. Voncento is only used when 
treatment with another medicine, desmopressin, is not effective alone or cannot be given. 
 
VWF and FVIII are involved in blood clotting. Lack of either factor means that blood does not clot as 
quickly as it should so there is an increased tendency to bleed. The replacement of VWF and FVIII by 
Voncento will temporarily repair the blood clotting mechanisms. 
 
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 prescribe you Voncento with the number of 
units of VWF specified. 
 
2. What you need to know before you use Voncento  
 
Do not use 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 administration, 
the batch number and the injected volume in your treatment diary. 
 
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 with all factor VIII medicines. These inhibitors, especially at high levels, 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 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  



44 

• 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. 
 
Children and adolescents 
 
The listed warnings and precautions 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 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 sodium per vial (main component of cooking/table salt). This is 
equivalent to 0.74 % of the recommended maximum daily dietary intake of sodium for an adult.  
 
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  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 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. 



45 

 
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 

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

 2 

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. 



46 

 3 

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 

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 

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 

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

 7 

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 

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. 



47 

 9 

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 if: 
• you notice symptoms of allergic reactions 

In some cases it may 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. 

• you notice that the medicine stops working properly (bleeding is not stopped). 
For children not previously treated with factor VIII medicines, inhibitor antibodies (see section 
2) may form very commonly (more than 1 in 10 patients); however 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 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 symptoms of an impaired perfusion in your extremities (e.g. cold and pale 
extremities) or vital organs (e.g. severe chest pain) 
There is a risk of formation of blood clots (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): 



48 

• Headache 
 
The following side effects have been observed commonly (may affect up to 1 in 10 people): 
• Increase in body temperature 
 
The following side effects have been 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 expected to be the same as in adults.  
 
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 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 carton. 
• Do not store above 25 °C.  
• Do not freeze.  
• The reconstituted product should preferably be used immediately.  
• If the reconstituted product is not administered immediately, storage times and conditions prior 

to use are the responsibility of the the user and should not exceed 24 hours at 2 to 8 °C. 
• Keep the vial in the 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 the 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; after reconstitution 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.  
 
See section “The following information is intended for healthcare professionals only” for further 
information. 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


49 

 
The other ingredients are: 
Calcium 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 solvent 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 immediate container of product and solvent vial consists 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 injections 
- 1 filter transfer device 20/20 
- One inner box containing: 
1 disposable 10 ml 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 10 ml water for injections 
- 1 filter transfer device 20/20 
- One inner box containing: 
1 disposable 10 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
Not all pack sizes may be marketed. 
 
Marketing Authorization Holder and Manufacturer 
 
CSL Behring GmbH 
Emil-von-Behring-Straße 76 
35041 Marburg 
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 20 
 

Lietuva 
CSL Behring GmbH 
Tel: +49 69 30584437 
 

България 
Новимед Фарма EООД 
Тел: +359 2 850 8617  

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

Česká republika Magyarország 



50 

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

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

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 
CSL Behring GmbH 
Tel: +49 69 30584437 
 

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 
MediSanus d.o.o. 
Tel: +386 1 25 71 496 
 

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

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

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

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

Κύπρος 
CSL Behring ΕΠΕ 
Τηλ: +30 210 7255 660 
 
 

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

Latvija 
CSL Behring GmbH 
Tel: +49 69 30584437 
 

United Kingdom 
CSL Behring UK Ltd. 
Tel: +44 1444 447405 
 

 
This leaflet was last revised in {MM/YYYY}. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

http://www.ema.europa.eu/


51 

 
 
---------------------------------------------------------------------------------------------------------- 
 
 
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. 
 



52 

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 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 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 factor VIII 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 factor 
VIII per kg body weight raises the plasma factor VIII 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 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 effectiveness in the individual case.  
 
In the case of the following haemorrhagic events, the factor VIII 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: 
 
Degree of haemorrhage / Type 
of surgical procedure 

Factor VIII level required 
(% or IU/dl) 

Frequency of doses (hours) / 
Duration of therapy (days) 

Haemorrhage   

Early haemarthrosis, muscle 
bleeding or oral bleeding 20 - 40 

Repeat 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 - 60 

Repeat infusion every 12-24 
hours for 3 - 4 days or more 
until pain and acute disability 
are resolved. 

Life-threatening haemorrhages: 60 - 100 Repeat infusion every 8 to 24 hours until threat is resolved. 
Surgery   

Minor surgery including tooth 
extraction 30 - 60 

Repeat infusion every 24 hours 
for at least 1 day, until healing is 
achieved. 

Major surgery 
80 - 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). 

 
Treatment monitoring 
During the course of treatment, appropriate determination of factor VIII levels 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 underweight or overweight patients. In the case of major surgical 



53 

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 term 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. 
 
 
Paediatric 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 be necessary. The frequency of administration should always be oriented to the 
clinical effectiveness in the individual case. 
 
Elderly 
No dose adjustment is necessary for the older people. 


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