Veyvondi

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 



2 

 

 

This medicinal product is subject to additional monitoring. This will allow quick identification of 

new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 

See section 4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

VEYVONDI 650 IU powder and solvent for solution for injection. 

VEYVONDI 1300 IU powder and solvent for solution for injection. 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

VEYVONDI 650 IU powder and solvent for solution for injection 

Each vial of powder contains nominally 650 International Units (IU) vonicog alfa. 

After reconstitution with the 5 mL solvent provided, VEYVONDI contains approximately 130 IU/mL 

vonicog alfa. 

 

VEYVONDI 1300 IU powder and solvent for solution for injection 

Each vial of powder contains nominally 1300 International Units (IU) vonicog alfa. 

After reconstitution with the 10 mL solvent provided, VEYVONDI contains approximately 130 IU/mL 

vonicog alfa 

The specific activity of VEYVONDI is approximately 110 IU VWF:RCo/mg protein. 

The potency of VWF (IU) is measured using the European Pharmacopeia ristocetin cofactor activity 

assay (VWF: RCo). The ristocetin cofactor activity of recombinant human von Willebrand factor was 

determined against the International Standard for von Willebrand factor concentrate (WHO). 

 

Vonicog alfa is a purified recombinant human von Willebrand factor (rVWF). It is manufactured by 

recombinant DNA (rDNA) technology in the Chinese Hamster Ovary (CHO) cell line without the 

addition of any exogenous human-or animal-derived protein in the cell culture process, purification or 

final formulation.  

 

The product contains only trace amounts of human recombinant coagulation factor VIII (≤ 0.01 IU 

FVIII / IU VWF: RCo) as determined using the European Pharmacopoeia chromogenic assay for 

factor VIII (FVIII). 

 

Excipient(s) with known effect 

Each 650 IU powder vial contains 5.2 mg sodium.  

Each 1300 IU powder vial contains 10.4 mg sodium. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder and solvent for solution for injection. 

 

The powder is a white to off-white lyophilized powder 

The solvent is a clear and colourless solution. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 



3 

 

 

VEYVONDI is indicated in adults (age 18 and older) with von Willebrand Disease (VWD), when 

desmopressin (DDAVP) treatment alone is ineffective or not indicated for the  

- Treatment of haemorrhage and surgical bleeding  
- Prevention of surgical bleeding. 
 

VEYVONDI should not be used in the treatment of Haemophilia A. 

 

4.2 Posology and method of administration 

 

Treatment of von Willebrand disease (VWD) should be supervised by a physician experienced in the 

treatment of haemostatic disorders.  

 

Posology 

Dosage and frequency of administration must be individualized according to clinical judgement and 

based on the patient´s weight, type and severity of the bleeding episodes/surgical intervention and 

based on monitoring of appropriate clinical and laboratory measures. Dose based on bodyweight may 

require adjustment in underweight or overweight patients. 

 

Generally, 1 IU/kg (VWF:RCo/VEYVONDI/vonicog alfa) raises the plasma VWF:RCo by 

0.02 IU/mL (2%). 

 

Haemostasis cannot be ensured until Factor VIII coagulant activity (FVIII:C) is at least 0.4 IU/mL 

(≥ 40% of normal activity). Depending on the patient’s baseline FVIII:C levels, a single infusion of 

rVWF will, in a majority of patients, lead to an increase above 40% in endogenous FVIII:C activity 

within 6 hours and will result in sustaining this level up to 72 hours post infusion. 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. If the patient’s baseline plasma FVIII:C level is 

< 40% or is unknown and in all situations where a rapid correction of haemostasis should be achieved, 

such as treatment of an acute haemorrhage, severe trauma or emergency surgery, it is necessary to 

administer a recombinant factor VIII product with the first infusion of VEYVONDI, in order to 

achieve a haemostatic plasma level of FVIII:C. 

 

However, if an immediate rise in FVIII:C is not necessary, or if the baseline FVIII:C level is sufficient 

to ensure haemostasis, the physician may decide to omit the co-administration of rFVIII at the first 

infusion with VEYVONDI. 
 

In case of major bleeding events or major surgeries requiring repeated, frequent infusions, monitoring 

of FVIII:C levels is recommended, to decide if rFVIII is required for subsequent infusions to avoid 

excessive rise of FVIII:C. 
 

Treatment of bleeding episodes (On demand treatment) 

 

Start of treatment 

The first dose of VEYVONDI should be 40 to 80 IU/kg body weight. Replacement levels of 

VWF:RCo > 0.6 IU/mL (60%) and FVIII:C > 0.4 IU/mL (40%) should be achieved. Dosing guidelines 

for treatment of minor and major haemorrhages are provided in Table 1. 

 

VEYVONDI should be administered with recombinant factor VIII if the FVIII:C levels are < 40%, or 

are unknown, to control bleeding. The rFVIII dose should be calculated according to the difference 

between the patient’s baseline plasma FVIII:C level, and the desired peak FVIII:C level to achieve an 

appropriate plasma FVIII:C level based on the approximate mean recovery of 0.02 (IU/mL)/(IU/kg). 

The complete dose of VEYVONDI should be administered followed by rFVIII within 10 minutes. 

 

Calculating dose: 

VEYVONDI dose [IU] = dose [IU/kg] x weight [kg] 



4 

 

 

 

Subsequent infusions: 

A subsequent dose of 40 IU to 60 IU/kg of VEYVONDI should be infused every 8 to 24 hours as per 

the dosing ranges in Table 1, or as long as clinically appropriate. In major bleeding episodes, maintain 

trough levels of VWF:RCo greater than 50% for as long as deemed necessary. 

 

Based on experience from clinical studies, once VWF has been replaced, endogenous FVIII levels will 

remain normal or near normal as long as VEYVONDI is continued to be administered.  

 

Table 1 

Dosing recommendations for the treatment of minor and major haemorrhages 
 

Haemorrhage 
 Initial dose a 

(IU VWF:RCo/kg body weight) 

Subsequent dose 

 

Minor 

(e.g. epistaxis, oral bleeding, 

menorrhagia) 

40 to 50 IU/kg 

40 to 50 IU/kg every 8 to 

24 hours (or as long as deemed 

clinically necessary) 

Major b 

(e.g. severe or refractory 

epistaxis, menorrhagia, 

gastrointestinal bleeding, 

central nervous system trauma, 

haemarthrosis, or traumatic 

haemorrhage) 

50 to 80 IU/kg 

40 to 60 IU/kg every 8 to 

24 hours for approximately 2-

3 days (or as long as deemed 

clinically necessary) 

aIf rFVIII is administered, see rFVIII package insert for reconstitution and administration instructions. 
bA bleed could be considered major if red blood cell transfusion is either required or potentially indicated or if 

bleeding occurs in a critical anatomical site (e.g., intracranial or gastrointestinal haemorrhage). 

 

Prevention of bleeding/haemorrhage and treatment in case of elective surgery 

 

Prior to Surgery: 

In patients with inadequate levels of FVIII, a dose of 40-60 IU/kg VEYVONDI should be 

administered 12-24 hours prior to initiating elective surgery (pre-operative dose), to ensure pre-

operative endogenous FVIII levels of at least 0.4 IU/mL for minor and at least 0.8 IU/mL for major 

surgery. 

 

For prevention of excessive bleeding in case of elective surgery, within 3 hours prior to initiation of 

any surgical procedure, the FVIII:C levels should be assessed. If the FVIII:C levels are at the 

recommended target level of:  

- at least 0.4 IU/mL for minor and oral surgery and 
- at least 0.8 IU/mL for major surgery, 

a dose of VEYVONDI alone should be administered within 1 hour prior to the procedure.  

 

If the FVIII:C levels are not at the recommended target levels, rFVIII should be administered in 

addition to vonicog alfa to raise VWF:RCo and FVIII:C, within 1 hour prior to the procedure. Please 

refer to Table 2 for FVIII:C recommended target levels. The dose depends on VWF and FVIII levels 

of the patient, the type and severity of the expected bleeding. 

 

 

Table 2 

Recommended Target Peak Plasma Levels of VWF:RCo and FVIII:C to be Achieved Prior to 

Surgery for the Prevention of Excessive Bleeding During and After Surgery 

Type of VWF:RCo FVIII:C Target Calculation of rVWF dose (to be 



5 

 

 

Surgery Target Peak 

Plasma Level 

Peak Plasma 

Level a 
administered within 1 hour prior to 

surgery) (IU VWF:RCo required) 

Minor 
0.50 – 

0.60 IU/mL 

0.40 – 

0.50 IU/mL 
∆b VWF:RCo x BW (kg) /IR c 

Major 1 IU/mL 0.80 - 1 IU/mL ∆b VWF:RCo x BW (kg) /IR c 
a Additional rFVIII may be required to attain the recommended FVIII:C target peak plasma levels. Dosing 

guidance should be done based on the IR. 
b ∆ = Target peak plasma VWF:RCo – baseline plasma VWF:RCo 
cIR = Incremental Recovery as measured in the subject. If the IR is not available, assume an IR of 0.02 IU/mL 

per IU/kg. 

 

During and After Surgery: 

After the initiation of the surgical procedure, the VWF:RCo and FVIII:C plasma levels should be 

monitored and the intra- and post-operative substitution regimen should be individualised according to 

the PK results, intensity and duration of the haemostatic challenge, and the institution’s standard of 

care. In general, the frequency of VEYVONDI dosing for post-operative substitution should range 

from twice a day to every 48 hours. Please refer to Table 3 for treatment recommendations for 

subsequent maintenance doses. 
 

Table 3 

Recommended Target Trough Plasma Levels of VWF:RCo and FVIII:C and  

Minimum Duration of Treatment for Subsequent Maintenance Doses  

for the Prevention of Excessive Bleeding After Surgery 

Type of 

Surgery 

VWF:RCo 

Target Trough Plasma 

Level 

FVIII:C 

Target Trough Plasma 

Level 
Minimum 

Duration 

of 

treatment 

Frequency of 

dosing Up to 72 

hours post 

surgery 

After 

72 hours 

post 

surgery 

Up to 72 

hours post 

surgery 

After 

72 hours 

post 

surgery 

Minor 
≥ 

0.30 IU/mL 
- 

> 

0.40 IU/mL 

- 

 48 hours 
Every 12-24 hrs / 

every other day 

Major 
> 

0.50 IU/mL 

> 

0.30 IU/mL 

> 

0.50 IU/mL 

> 

0.40 IU/mL 
72 hours 

Every 12-24 hrs / 

every other day 

 

Paediatric population 

 

The safety and efficacy of VEYVONDI in children aged 0 to 18 years have not yet been established. 

No data are available.  

 

Method of administration 

 

VEYVONDI is for intravenous use. The reconstituted product should be inspected visually prior to 

administration.  

 

The rate of administration should be slow enough to ensure the comfort of the patient, up to a 

maximum of 4 mL/min. The patient should be observed for any immediate reaction. If any reaction, 

such as tachycardia, occurs that might be related to the administration of the product, the rate of 

infusion should be reduced or stopped as required by the clinical condition of the patient. When co-

administration of rVWF and rFVIII is considered necessary, they can be pre-mixed in a single syringe 

to achieve the appropriate dose. The contents of each vial of rVWF and rFVIII can be drawn into a 

single syringe by using a separate unused reconstitution device (see section 6.2 for incompatibilities). 

 

For instructions on reconstitution of the medicinal product before administration, see section 6.6. 

 



6 

 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

Known allergic reaction to mouse or hamster proteins. 

 

4.4 Special warnings and precautions for use 

 

In actively bleeding patients it is recommended to co-administer a FVIII product with VEYVONDI as 

a first line treatment and depending on the FVIII activity levels (see section 4.2). 

 

Traceability 

In order to improve the traceability of biological medicinal products, the name and the batch number 

of the administered product should be clearly recorded. 

 

Hypersensitivity reactions 

Hypersensitivity reactions (including anaphylaxis) have occurred. Patients and/or their caregivers 

should be informed of the early signs of hypersensitivity reactions, which may include but are not 

limited to tachycardia, tightness of the chest, wheezing and/or acute respiratory distress, hypotension, 

generalised urticaria, pruritus, rhinoconjunctivitis, angioedema, lethargy, nausea, vomiting, 

paresthesia, restlessness, and may progress to anaphylactic shock. In case of shock, standard medical 

treatment for shock should be implemented.  

 

Patients should be closely monitored and carefully observed for any symptoms throughout the infusion 

period. If signs and symptoms of severe allergic reactions occur, immediately discontinue 

administration of VEYVONDI and provide appropriate supportive care. 

 

Adequate medical treatment and provisions should be available for immediate use for a potential 

anaphylactic reaction, especially for patients with a history of allergic reactions. 

 

VEYVONDI contains trace amounts of mouse immunoglobulin G (MuIgG) and Hamster proteins 

(less than or equal to 2 ng/IU VEYVONDI). Patients treated with this product may develop 

hypersensitivity reactions to these non-human mammalian proteins. VEYVONDI contains trace 

amounts of recombinant coagulation factor VIII.  

 

Thrombosis and Embolism 

There is a risk of occurrence of thrombotic events, particularly in patients with known clinical or 

laboratory risk factors for thrombosis including low ADAMTS13 levels. Therefore, patients at risk 

have to be monitored for early signs of thrombosis, and prophylaxis measures against 

thromboembolism should be instituted according to current recommendations and standard of care.  

 

In patients requiring frequent doses of VEYVONDI in combination with recombinant factor VIII, 

plasma levels for FVIII:C activity should be monitored to avoid sustained excessive FVIII:C plasma 

levels, which may increase the risk of thrombotic events. 

Any FVIII that would be administered along with VEYVONDI should be a pure FVIII product. A 

combination with a FVIII product containing VWF would pose an additional risk of thrombotic 

events. 

 

Neutralizing antibodies (Inhibitors) 

Patients with VWD, especially Type 3, may develop neutralising antibodies (inhibitors) to von 

Willebrand factor. If the expected plasma levels of (VWF:RCo) are not attained, or if bleeding is not 

controlled with an appropriate dose, an appropriate assay should be performed to determine if a von 

Willebrand factor inhibitor is present. In patients with high levels of anti-VWF antibodies, von 

Willebrand factor therapy may not be effective and other therapeutic options should be considered. 

 



7 

 

 

Treatment of VWD patients who have high-titer binding antibodies (due to previous treatment with 

pdVWF) may require a higher dose to overcome the binding antibody effect and such patients could 

be managed clinically by administration of higher doses of vonicog alfa based on the PK data for each 

individual patient. 

 

Excipient related considerations 

This medicinal product contains 5.2 mg sodium in each 650 IU vial or 10.4 mg sodium in each 

1300 IU vial. This is equivalent to 2.2% of the WHO recommended maximum daily intake of 2 g 

sodium for an adult, assuming a body weight of 70 kg and a dose of 80 IU/kg body weight. This is to 

be taken into consideration by patients on a controlled sodium diet. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No interactions of human von Willebrand factor products with other medicinal products are known. 

 

4.6 Fertility, pregnancy and lactation 

 

Animal reproduction studies have not been conducted with VEYVONDI. 

 

Pregnancy 

Experience in the treatment of pregnant or breast-feeding women is not available. VEYVONDI should 

be administered to pregnant woment only if clearly indicated, taking into consideration that delivery 

confers an increased risk of haemorrhagic events in these patients. 

 

Breast-feeding 

It is unknown whether VEYVONDI is excreted in human milk.Therefore, VEYVONDI should be 

administered to lactating von Willebrand factor deficient women only if clearly indicated. Healthcare 

professionals should balance the potential risks and only prescribe VEYVONDI if needed 

 

Fertility 

The effects of VEYVONDI on fertility have not been established. 

 

4.7 Effects on ability to drive and use machines 

 

VEYVONDI has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

During treatment with VEYVONDI the following adverse reactions may occur: 

Hypersensitivity or allergic reactions, thromboembolic events, inhibitor formation against VWF. 

 

Tabulated list of adverse reactions 

The table 4 lists the adverse reactions reported in clinical trials, post-authorisation safety studies or 

post-marketing reporting. 

Frequency categories are defined 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). Within each frequency 

grouping, undesirable effects are presented in the order of decreasing seriousness. 

 



8 

 

 

Table 4 

Summary of Adverse Reactions reported in Clinical Trials, Post-authorisation safety studies 

or post-marketing with VEYVONDI  

in von Willebrand Disease  

MedDRA System Organ Class 

(SOC) 

Adverse Reaction by 

Preferred Term (PT) 

Frequency 

Category by 

Subject 

Number and 

Frequency by 

Subjecta 

(N=80) 

n (%) 

Nervous system disorders 

Dizziness Common 3 (3.75) 

Vertigo Common 2 (2.50) 

Dysgeusia Common 1 (1.25) 

Tremor Common 1 (1.25) 

Cardiac disorders Tachycardia Common 1 (1.25) 

Vascular disorders 

Deep venous thrombosis Common 1 (1.25) 

Hypertension Common 1(1.25) 

Hot flush Common 1 (1.25) 

Gastrointestinal disorders 
Vomiting Common 3 (3.75) 

Nausea Common 3 (3.75) 

Skin and subcutaneous tissue 

disorders 
Pruritus generalized Common 2 (2.50) 

General disorders and 

administration site conditions 

Chest discomfort Common 1 (1.25) 

Infusion site paraesthesia Common 1 (1.25) 

Infusion-related reaction 

(including tachycardia, 

flushing, rash, dyspnea, 

blurred vision) 

Not known  

Investigations 

Electrocardiogram T 

wave inversion 
Common 1 (1.25) 

Heart rate increased Common 1 (1.25) 

Immune system disorders Anaphylactic reaction Not known  
a Frequency by Subject: Total number of subjects experiencing the AE (related and unrelated) divided by 

total number of subjects (N) and multiplied by 100. Not known: cannot be estimated from the available data 

(observed during post-marketing surveillance). 

 

 

Description of selected adverse reactions 

In clinical trials, one case of clinically asymptomatic deep vein thrombosis (DVT) was reported for a 

subject in the surgery study who had total hip replacement. 

In addition, one post-marketing case of DVT has been reported spontaneously for an elderly patient. 

 

Hypersensitivity 

There is a possibility of developing hypersensitivity or allergic reactions (which may include 

angioedema, burning and stinging at the infusion site, chills, flushing, rhinoconjunctivitis, generalised 

urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the 

chest, tingling, vomiting, wheezing) which may in some cases progress to anaphylaxis (including 

shock). 

 

Patients with von Willebrand disease, especially Type 3, may very rarely develop neutralising 

antibodies (inhibitors) to von Willebrand factor. If such inhibitors occur, the condition may manifest 

itself as an inadequate clinical response. Such antibodies may occur in close association with 

hypersensitivity or anaphylactic reactions. Therefore, patients experiencing hypersensitivity or 

anaphylactic reactions should be tested and evaluated for the presence of an inhibitor. 

 



9 

 

 

In all such cases, it is recommended that a specialised haemophilia centre be contacted. 

 

Thrombogenicity 

There is a risk of occurrence of thrombotic events, particularly in patients with known clinical or 

laboratory risk factors including low ADAMTS13 levels. Therefore, patients at risk have to be 

monitored for early signs of thrombosis, and prophylaxis measures against thromboembolism should 

be instituted according to current recommendations and standard of care.  

 

Immunogenicity 

The immunogenicity of VEYVONDI was assessed in clinical trials by monitoring the development of 

neutralizing antibodies against VWF and FVIII, as well as binding antibodies against VWF, Furin, 

Chinese Hamster Ovary (CHO) protein and mouse IgG. No treatment-emergent development of 

neutralizing antibodies against human VWF or neutralizing antibodies against human rFVIII was 

observed. One of the 80 subjects who received VEYVONDI peri-operatively in clinical studies 

developed treatment-emergent binding antibodies against VWF following a surgery for whom no 

adverse events or lack of haemostatic efficacy has been reported. Binding antibodies against impurities 

such as rFurin, CHO-protein or mouse IgG were not observed after treatment with VEYVONDI. 

 

 

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 

 

No symptoms of overdose with von Willebrand factor have been reported. Thromboembolic events 

may occur in case of major overdose. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: Antihaemorrhagics: blood coagulation factor von Willebrand factor. ATC 

code: B02BD10 

 

Mechanism of action 

VEYVONDI is a recombinant human von Willebrand factor (rVWF). VEYVONDI behaves in the 

same way as endogenous von Willebrand factor. 

 

Administration of VEYVONDI allows correction of the haemostatic abnormalities exhibited by 

patients who suffer from von Willebrand factor deficiency (von Willebrand's disease) at two levels: 

- VEYVONDI re-establishes platelet adhesion to the vascular sub-endothelium at the site of 
vascular damage (as it binds both to the vascular sub-endothelium matrix (e.g. collagen) 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. 

- VEYVONDI produces delayed correction of the associated factor VIII deficiency. Administered 
intravenously, VEYVONDI binds to endogenous factor VIII (which is produced normally by the 

patient), and by stabilising this factor, avoids its rapid degradation. Because of this, 

administration of VEYVONDI restores the FVIII:C level to normal as a secondary effect after 

the first infusion Administration of the FVIII:C rises above 40% within 6 hours and peaks 

within 24 hours in a majority of patients, depending on the baseline FVIII:C level. 

 

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


10 

 

 

VEYVONDI is a rVWF that contains ultra-large multimers in addition to all of the multimers found in 

plasma as it is not exposed to proteolysis by ADAMTS13 during the manufacturing process. 

 

Clinical efficacy and safety 

The clinical safety, efficacy and PK data were assessed in 3 completed trials, (070701, 071001 and 

071101) which enrolled patients with VWD. A total of 92 unique subjects (80 unique subjects with 

VWD in studies 070701, 071001 and 071101 and 12 subjects with Haemophilia A in study 071104) 

were exposed to VEYVONDI during clinical development. 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

VEYVONDI in all subsets of the paediatric population in the treatment of von Willebrand Disease (see 

section 4.2 for information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

The pharmacokinetics (PK) of VEYVONDI were determined in three clinical studies by assessing the 

plasma levels of VWF:RCo, von Willebrand Factor Antigen (VWF:Ag), and von Willebrand Collagen 

Binding Activity (VWF:CB). In all three studies, subjects were evaluated in the non-bleeding state. 

Sustained increase of FVIII:C was observed by six hours after a single infusion of VEYVONDI.  

 

Table 6 summarizes the PK of VEYVONDI after 50 IU/kg VWR:RCo (PK50) or 80 IU/kg VWF:RCo 

(PK80) infusions . The mean duration of infusion was 16.5 minutes (SD ± 3.51 minutes) for 50 IU/kg 

(PK50) and 11.8 minutes (± 2.86 minutes) for 80 IU/kg VWF:RCo (PK80). 

 

Table 5 

Pharmacokinetic Assessment of VWF:RCo f 

 
Parameter Phase 1 PK50 

VEYVONDI with 

octocog alfag 

(Study 070701) 

 

Mean (95% CI) 

SD 

Phase 3 PK50 

VEYVONDI 

(Study 071001) 

 

Mean (95% CI) 

SD 

Phase 3 PK80 

VEYVONDI 

(Study 071001) 

 

Mean (95% CI) 

SD 

Surgery PK50 

VEYVONDI 

(Study 071101) 

 

Mean (95% CI) 

SD 

T1/2a 19.3 (14.3; 24.3) 

10.99 

22.6 (19.5; 25.7) 

5.34 

19.1 (16.7; 21.5) 

4.32 

17.8 (12.9; 22.8) 

7.34 

Clb 0.04 (0.03; 0.05) 

0.028 

0.02 (0.02; 0.03) 

0.005 

0.03 (0.02; 0.03) 

0.009 

0.03 (0.02; 0.04) 

0.011 

IR at 

Cmaxc 

1.7 (1.4; 2.0) 

0.62 

1.9 (1.6; 2.1) 

0.41 

2.0 (1.7; 2.2) 

0.39 

2.0 (1.7; 2.3) 

0.45 

AUC0-infd 1541.4 (1295.7; 1787.2) 

554.31 

2105.4 (1858.6; 2352.3) 

427.51 

2939.0 (2533.2; 3344.8) 

732.72 

1834.4 (1259.0; 2409.7) 

856.45 

AUC0-

inf/Dosee 

33.4 (27.2; 39.5) 

13.87 

42.1 (37.3; 46.9) 

8.31 

36.8 (31.8; 41.8) 

8.97 

37.5 (25.3; 49.7) 

18.14 
a[hours], b[dL/kg/hours], c[(IU/dL)/(U VWF:RCo/kg)] d[(h*IU/dL)] e[(h*IU/dL)/(IU VWF:RCo/kg)] 
f[VWF:RCo assays with different sensitivity and working ranges were used: Phase 1: automated assay 0.08 – 

1.50 IU/mL and sensitive manual assay 0.01 – 0.08 IU/mL; Phase 3: automated assay 0.08 – 1.50 IU/mL 
g This trial was done using ADVATE, a recombinant factor VIII 

 

An exploratory analysis of combined data from studies 070701 and 071001 indicated a statistically 

significantly (at the 5% level) longer mean residence time, a statistically significantly (at the 5% level) 

longer terminal half-life and statistically significantly (at the 5% level) larger AUC0-inf regarding 

VWF:RCo following administration with VEYVONDI (50 IU/kg VWF:RCo) and combined 

administration of VEYVONDI and octocog alfa (50 IU/kg VWF:RCo and 38.5 IU/kg rFVIII) than 

after administration of pdVWF and pdFVIII (50 IU/kg pdVWF:RCo and 38.5 IU/kg pdFVIII).  



11 

 

 

 

5.3 Preclinical safety data 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction 

and development. 

 

No investigations on carcinogenicity, fertility impairment and fetal development have been conducted. 

In a human ex vivo placenta perfusion model, it has been demonstrated that VEYVONDI does not 

cross the human placenta barrier. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Powder 

Sodium citrate 

Glycine 

Trehalose dihydrate 

Mannitol 

Polysorbate 80 

 

Solvent 

Water for injections 

 

6.2 Incompatibilities 

 

Clinical and compatibility studies were conducted to administer vonicog alfa (human von Willebrand 

factor) with octocog alfa (human coagulation factor) in the same syringe. The rVWF and rFVIII can be 

pre-mixed in a single syringe to achieve the appropriate dose (see section 4.2 for mode of 

administration). This medicinal product must not be mixed with other medicinal products except those 

mentioned in section 6.6  

 

6.3 Shelf life 

 

Unopened vial 

3 years. 

 

Shelf-life after reconstitution: 

Chemical and physical in-use stability has been demonstrated for 3 hours at 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, unless reconstitution has taken place in 

controlled and validated aseptic conditions.  

 

6.4 Special precautions for storage 

 

Powder 

Do not store above 30°C. 

Do not freeze. 

Store in the original package in order to protect from light.  

 

After reconstitution 

For storage conditions after reconstitution of the medicinal product, see section 6.3. 

 



12 

 

 

6.5 Nature and contents of container 

 

VEYVONDI 650 IU powder and solvent for solution for injection 

Each pack contains: 

- powder in a vial (type I glass), with a butyl rubber stopper 
- 5 mL of solvent in a vial (type I glass), with a rubber stopper (chlorobutyl) 
- one reconstitution device (Mix2Vial) 
 

 VEYVONDI 1300 IU powder and solvent for solution for injection 

Each pack contains: 

- powder in a vial (type I glass), with a butyl rubber stopper 
- 10 mL of solvent in a vial (type I glass), with a rubber stopper (bromobutyl) 
- one reconstitution device (Mix2Vial) 

 

6.6 Special precautions for disposal and other handling 

 

General Instructions 

- Check the expiry date, and ensure that the VEYVONDI powder and water for injections 
(solvent) are at room temperature prior to preparation. Do not use after the expiry date stated on 

the labels and carton. 

- Use antiseptic technique (clean and low-germ conditions) and a flat work surface during the 
reconstitution procedure. Wash your hands and put on clean exam gloves (the use of gloves is 

optional). 

- Use the reconstituted product (after mixing the powder with the supplied water) as soon as 
possible and within three hours. You can store the reconstituted product at room temperature not 

to exceed 25° C for up to three hours. 

- Ensure that the VEYVONDI powder vial and the sterilised water for injections (solvent) are at 
room temperature prior to preparation. 

- Use plastic syringes with this product because proteins in the product tend to stick to the surface 
of glass syringes. 

- Do not mix vonicog alfa with other medicinal products except for rFVIII. 
 

Instructions for Reconstitution and application 

 

 Steps Image example 
1 Remove the caps from the VEYVONDI powder and solvent vials to 

expose the center of the rubber stoppers. 

 
2 Disinfect each stopper with a separate sterile alcohol swab (or other 

suitable sterile solution suggested by your doctor or haemophilia 

treatment center) by wiping the stopper for several seconds. Allow 

the rubber stopper to dry. Place the vials on a flat surface. 

 
3 Open the Mix2Vial device package by completely peeling away the 

lid, without touching the inside of the package. Do not remove the 

Mix2Vial device from the package. 

NA 



13 

 

 

4 Turn the package with the Mix2Vial device upside down and place it 

over the top of the solvent vial. Firmly insert the blue plastic spike of 

the device into the center of the solvent vial stopper by pushing 

straight down. Grip the package at its edge and lift it off the 

Mix2Vial device. Be careful not to touch the clear plastic spike. The 

solvent vial now has the Mix2Vial device connected to it and is 

ready to be connected to the VEYVONDI vial. 
 

5 To connect the solvent vial to the VEYVONDI vial, turn the solvent 

vial over and place it on top of the vial containing VEYVONDI 

powder. Fully insert the clear plastic spike into the VEYVONDI vial 

stopper by firmly pushing straight down. This should be done right 

away to keep the liquid free of germs. The solvent will flow into the 

VEYVONDI vial by vacuum. Check that all the solvent has 

transferred. Do not use if the vacuum has been lost and the solvent 

does not flow into the VEYVONDI vial. 

 
6 Gently and continuously swirl the connected vials or allow the 

reconstituted product to stand for 5 minutes then gently swirl to 

ensure the powder is completely dissolved. Do not shake. Shaking 

will adversely affect the product. Do not refrigerate after 

reconstitution. 

 
7 Disconnect the two sides of the Mix2Vial from each other by 

holding the clear plastic side of the Mix2Vial device attached to the 

VEYVONDI vial with one hand and the blue plastic side of the 

Mix2Vial device attached to the solvent vial with the other hand. 

Turn the blue plastic side counterclockwise and gently pull the two 

vials apart. Do not touch the end of the plastic connector attached to 

the VEYVONDI vial containing the dissolved product. Place the 

VEYVONDI vial on a flat work surface. Discard the empty solvent 

vial. 
 

8 Draw air into the empty, sterile disposable plastic syringe by pulling 

back on the plunger. The amount of air should equal the amount of 

reconstituted VEYVONDI that you will withdraw from the vial. 

 
9 Leaving the VEYVONDI vial (containing the reconsituted product) 

on your flat work surface, connect the syringe to the clear plastic 

connector and turning the syringe clockwise. 

 



14 

 

 

10 Hold the vial with one hand and use the other hand to push all the air 

from the syringe into the vial.  

 
11 Flip connected syringe and VEYVONDI vial so the vial is on top. 

Be sure to keep the syringe plunger pressed in. Draw the 

VEYVONDI into the syringe by pulling plunger back slowly. 

 
12 Do not push and pull solution back and forth between syringe and 

vial. Doing so may harm medicine. When ready to infuse, disconnect 

the syringe by turning it counterclockwise. Inspect the syringe 

visually for particulate matter; the solution should be clear and 

colourless. If flakes or particles are seen, do not use the solution and 

notify your doctor. 

 
13 If you need more than one vial of VEYVONDI to make up your 

dose: 

• Leave the syringe attached to the vial until an additional 
vial is prepared. 

• Use the reconstitution steps above (2 to 8) to prepare the 
additional vial of VEYVONDI using a fresh Mix2Vial 

device for each vial.  

 

14 The contents of two vials may be drawn into a single syringe.  

NOTE: When pushing air into a second vial of VEYVONDI to be 

pooled into a syringe, orient the vial and connected syringe with the 

vial on top. 

 

 

Instructions for Administration 

 

Inspect the prepared solution in the syringe for particulate matter and discoloration prior to 

administration (the solution should be clear, colourless and free from particles). It is not uncommon 

for a few flakes or particles to remain in the product vial after reconstitution. The filter included in 

the Mix2Vial device removes those particles completely. Filtration does not influence dosage 

calculations. The solution in the syringe should not be used if it is cloudy or contains flakes or 

particles after filtration. 

 

1. Attach the infusion needle to a syringe containing VEYVONDI solution. For comfort, a winged 
(butterfly) infusion set is preferred. Point the needle up and remove any air bubbles by gently 

tapping the syringe with your finger and slowly and carefully pushing air out of the syringe and 

needle. 

2. Apply a tourniquet and get the infusion site ready by wiping the skin well with a sterile alcohol 
swab (or other suitable sterile solution suggested by your doctor or haemophilia treatment center). 



15 

 

 

3. Insert the needle into the vein and remove the tourniquet. Slowly infuse VEYVONDI. Do not 
infuse any faster than 4 mL per minute. Disconnect the empty syringe. If your dose requires 

multiple syringes, attach and administer each additional syringe of VEYVONDI one at a time. 

Note:  

Do not remove butterfly needle until all syringes have been infused and do not touch the Luer port 

that connects to the syringe. 

If recombinant factor VIII has been prescribed, administer recombinant factor VIII within 10 

minutes after infusion of VEYVONDI has been completed. 

4. Take the needle out of the vein and use sterile gauze to put pressure on the infusion site for several 
minutes. 

 

In case large volumes of VEYVONDI are required, it is possible to pool two vials of VEYVONDI 

together. The contents of each reconstituted product of VEYVONDI can be drawn in a single syringe. 

However, in these cases the initially reconstituted solution of VEYVONDI should not be diluted any 

further. 

 

The solution should be slowly administered intravenously (see section 4.2) not exceeding 4 mL/min. 

Do not recap the needle. Place the needle, syringe, and empty VEYVONDI and solvent vial(s) in a 

hard-walled sharps container for proper disposal. Do not dispose of these supplies in ordinary 

household trash. 

 

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

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

Industriestraße 67 

1221 Vienna  

Austria 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/18/1298/001 

EU/1/18/1298/002 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

 

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/


16 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 

MANUFACTURER(S) 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 

 

 



17 

 

 

A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturers of the biological active substance  

Baxalta Manufacturing Sarl 

Route de Pierre-a-Bot 111 

CH-2000 Neuchatel 

SWITZERLAND 

 

Baxter AG 

Uferstrasse 15 

2304 Orth an der Donau 

AUSTRIA 

 

Name and address of the manufacturers responsible for batch release 

Baxter AG 

Industriestrasse 67 

A-1221 Vienna 

AUSTRIA 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

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). 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  

• Periodic safety update reports (PSURs) 

 

The requirements for submission of PSURs for this medicinal product are set out in the list of 

Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and 

any subsequent updates published on the European medicines web-portal. 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk management plan (RMP) 

 

The marketing authorisation holder (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. 



18 

 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new 

information being received that may lead to a significant change to the benefit/risk profile 

or as the result of an important (pharmacovigilance or risk minimisation) milestone being 

reached. 



19 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

 



20 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



21 

 

 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (650 IU) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

VEYVONDI 650 IU powder and solvent for solution for injection  

vonicog alfa (recombinant human von Willebrand factor) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial contains 650 IU vonicog alfa, approx. 130 IU/mL after reconstitution with 5 mL water for 

Injections 

Specific activity: approx. 110 IU VWF:RCo/mg protein 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: Sodium citrate, glycine, trehalose dihydrate, mannitol, polysorbate 80, and water for 

injections. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

Contents: 1 powder vial, 1 vial with solvent (5 mL), 1 Mix2Vial device 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before 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: 

 

Use immediately or within 3 hours after reconstitution. 



22 

 

 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 30°C. 

Do not freeze. 

Store in the original package 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 

 

Baxalta Innovations GmbH 

Industriestraße 67 

1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/18/1298/001 

 

13. BATCH NUMBER 

 

Lot: 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

VEYVONDI 650 IU 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 



23 

 

 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (1300 IU) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

VEYVONDI 1300 IU powder and solvent for solution for injection  

vonicog alfa (recombinant human von Willebrand factor) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial contains1300 IU vonicog alfa, approx. 130 IU/mL after reconstitution with 10 mL Water for 

Injections 

Specific activity: approx. 110 IU VWF:RCo/mg protein 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: Sodium citrate, glycine, trehalose dihydrate, mannitol, polysorbate 80 and water for 

injections. See leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

Contents: 1 powder vial , 1 vial with solvent (10ml), 1 Mix2Vial device 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before 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: 

 

Use immediately or within 3 hours after reconstitution. 



24 

 

 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 30°C. 

Do not freeze. 

Store in the original package 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 

 

Baxalta Innovations GmbH 

Industriestraße 67 

1221 Vienna  

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/18/1298/002 

 

13. BATCH NUMBER 

 

Lot: 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

VEYVONDI 1300 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 LABEL 

 

 

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

 

VEYVONDI 650 IU powder  

vonicog alfa 

IV  

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use only. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 



26 

 

 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

POWDER VIAL LABEL 

 

 

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

 

VEYVONDI 1300 IU powder  

vonicog alfa 

IV  

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use only. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

4. BATCH NUMBER 

 

Lot: 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 



27 

 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

SOLVENT VIAL LABEL (5mL) 

 

 

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

 

Solvent for VEYVONDI 

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 

 

 



28 

 

 

 

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 

 

Solvent for VEYVONDI 

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 

 

 



29 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



30 

 

 

Package leaflet: Information for the patient 

 

VEYVONDI 650 IU powder and solvent for solution for injection 

VEYVONDI 1300 IU powder and solvent for solution for injection 

vonicog alfa 

 

This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of 

section 4 for how to report side effects.  

 

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 any further questions, ask your doctor. 
- This medicine has been prescribed for you only. 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. This includes any possible side effects not listed 
in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What VEYVONDI is and what it is used for  

2. What you need to know before you use VEYVONDI  

3. How to use VEYVONDI  

4. Possible side effects  

5. How to store VEYVONDI  

6. Contents of the pack and other information 

 

 

1. What VEYVONDI is and what it is used for 

 

VEYVONDI contains the active substance vonicog alfa, which is a recombinant human von 

Willebrand factor (rVWF). It behaves in the same way as natural human von Willebrand factor (VWF) 

in the body. VWF is the carrier molecule for coagulation factor VIII and is involved in blood clotting 

making platelets stick to wounds and so helps to form a blood clot. Lack of VWF increases the 

tendency to bleed. 

 

VEYVONDI is used to treat and control bleeding episodes and to prevent bleeding during surgery in 

adult patients (aged 18 years and older) with von Willebrand disease. It is used when treatment with 

another medicine, desmopressin, is not effective or cannot be given. 

 

Von Willebrand disease is an inherited bleeding disorder caused by the lack or an insufficient amount 

of von Willebrand factor. In patients with the disease the blood does not clot normally leading to a 

prolonged bleeding time. Administration of von Willebrand factor (VWF) allows for correction of von 

Willebrand factor deficiency. 

 

 

2. What you need to know before you use VEYVONDI  

 

Do not use VEYVONDI 

- if you are allergic to vonicog alfa or any of the other ingredients of this medicine (listed in 
section 6) 

- if you are allergic to mouse or hamster proteins 
 

If you are unsure about this, ask your doctor.  



31 

 

 

 

Warnings and precautions  

Talk to your doctor before using VEYVONDI  

There is a  risk that you may experience a hypersensitivity reaction (a severe, sudden allergic reaction) 

to VEYVONDI. Your doctor should inform you about early signs of severe allergic reactions such as 

increased heart rate, rash, hives, wheals, generalised itching, swelling of lips and tongue, difficulty in 

breathing, wheezing, tightness in the chest, fast heartbeat, stuffy nose, red eyes,general feeling of 

being unwell, and dizziness. These could be early symptoms of a hypersensitivity reaction. If any of 

these symptoms occur, stop the infusion immediately and contact your doctor. Severe symptoms, 

including difficulty in breathing and dizziness, require prompt emergency treatment. 

 

Patients developing inhibitors 

Inhibitors (antibodies) against the VWF may occur in some patients receiving the medicine.These 

inhibitors, especially at high levels, could cause the treatment to stop working properly. You will be 

monitored carefully for the possibility of having developed these inhibitors. 

- If your bleeding is not controlled with VEYVONDI, tell your doctor immediately. 
 

If your plasma VWF or factor VIII fail to reach the expected levels with VEYVONDI based on the test 

results followed by your doctor, or if bleeding is not adequately controlled, it could be due to the 

presence of VWF or factor VIII antibodies. This will be checked by your doctor. You might need a 

higher dose of VEYVONDI, or a higher dose of factor VIII, or even a different medicine to control 

bleedings. Do not increase the total dose of VEYVONDI to control your bleeding without consulting 

your doctor. 

 

If you have previously been treated with plasma-derived VWF concentrates you may have reduced 

response to VEYVONDI due to pre-existing antibodies. Your doctor may adjust the dose according to 

your laboratory results.  

 

Thrombolism and embolism 

There is a risk of occurrence of thrombotic events if you have known clinical or laboratory risk 

factors.Therefore your doctor will monitor you for early signs of thrombosis. 

FVIII products may contain varying amounts of VWF. Therefore, any FVIII product that would be 

administered in combination with VEYVONDI should be a pure FVIII product.  

If you previously had problems with blood clots or vessel occlusion (thromboembolic complications), 

tell your doctor immediately. 

 

Children and adolescents 

VEYVONDI is not approved for use in children or adolescents below 18 years. 

 

Other medicines and VEYVONDI 

Tell your doctor if you are using, have recently used or might use 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 for advice before taking this medicine. 

 

Driving and using machines 

VEYVONDI is not likely to affect your ability to drive and use machines.  

 

VEYVONDI contains sodium 

This medicine contains 5.2 mg sodium in each 650 IU vial or 10.4 mg sodium in each 1300 IU vial. 

This is equivalent to 2.2% of the recommended maximum daily dietary intake of sodium for an adult, 

assuming 70 kg body weight and 80 IU/kg body weight. 

 

This should be taken into consideration if you are on a controlled sodium diet. 

 



32 

 

 

3. How to use VEYVONDI 

 

Your treatment with VEYVONDI will be supervised by a doctor who is experienced in the care of 

patients with von Willebrand disease.  

 

Your doctor will calculate your dose of VEYVONDI (in international units or IU). The dose depends 

on: 

- body weight,  
- the site of the bleeding 
- intensity of the bleeding,  
- your clinical condition,  
- the required surgery  
- the VWF activity levels in your blood after surgery  
- the severity of your disease 
 

Your doctor may test your blood to make sure that you have adequate levels of von Willebrand factor. 

This is particularly important if you are having major surgery. 

 

Treatment of bleeding episodes 

Your doctor will calculate the dose that is most appropriate for you, how often you should receive 

VEYVONDI and for how long.  

For minor bleeding (e.g. nose bleed, oral bleeding, menorrhagia), each initial dose is usually 40 to 50 

IU/kg and for major bleeding (severe or refractory nose bleed, menorrhagia, gastrointestinal bleeding, 

Central nervous system trauma, haemarthrosis, or traumatic haemorrhage), each initial dose is 50 to 80 

IU/kg. Subsequent doses (as clinically required) are 40 to 50 IU/kg every 8 to 24 hours for minor 

bleeds as long as deemed clinically necessary and for major bleeds 40 to 60 IU/kg for approximately 

2-3 days. 

 

If you feel that VEYVONDI is not working well enough, talk to your doctor. Your doctor will perform 

tests to make sure that you have adequate levels of von Willebrand factor. If you use VEYVONDI at 

home, your doctor will make sure that you are shown how to infuse it and how much to use. 

 

Prevention of bleeding in case of elective surgery 

For prevention of excessive bleeding your doctor will assess the FVIII:C levels within 3 hours before 

surgery. If your FVIII level is inadequate your doctor may give you a dose of 40-60 IU/kg 

VEYVONDI 12-24 hours (pre-operative dose) prior to initiating elective surgery in order to raise 

FVIII levels to the target level (0.4 IU/mL for minor and at least 0.8 IU/mL for major surgery). Within 

1 hour prior to surgery, you will receive a dose of VEYVONDI based on the assessment 3 hours 

before surgery. The dose depends on VWF and FVIII levels of the patient, the type and severity of the 

expected bleeding. 

 

How VEYVONDI is given 

VEYVONDI is usually infused into a vein (intravenously) by your doctor or nurse. Detailed 

instructions for reconstitution and admnistration are given at the end of this package leaflet. 

 

Use in children and adolescents 

VEYVONDI is not approved for use in children and adolescents below 18 years.  

 

If you use more VEYVONDI than you should 

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 

sure. If you infuse more VEYVONDI than recommended, tell your doctor as soon as possible. There 

may be a risk of developing blood clots (thrombosis) in case of an accidental high dose. 

 

If you forget to use VEYVONDI 

- Do not infuse a double dose to make up for a forgotten dose.  
- Proceed with the next infusion as scheduled and continue as advised by your doctor. 



33 

 

 

 

If you stop using VEYVONDI 

Do not stop using VEYVONDI without consulting your doctor. 

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

 

 

4. Possible side effects 

 

Like all medicines, this medicine may cause side effects, although not everybody gets them. 

 

You can have a serious allergic reaction to VEYVONDI. 

 

You must stop the infusion and contact your doctor immediately if you have any of the following 

early symptoms of severe allergic reactions: 

- rash or hives, itching all over the body, 
- tightness of the throat, chest pain or chest tightness, 
- difficulty breathing, light headedness, fast heartbeat, 
- dizziness, nausea or fainting. 
 

Side effects that have been reported with VEYVONDI that can occur commonly (up to 1 in 

10 patients) are: nausea, vomiting, tingling or burning at infusion site, chest discomfort, dizziness, 

vertigo, blood clots, hot flushes, itching, high blood pressure, muscle twitching, unusual taste, and 

increased heart rate. 

 

Reporting of side effects 

If you get any side effects, talk to your doctor. 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 VEYVONDI 

 

- 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 after EXP. The expiry 

date refers to the last day of that month. 

- Do not store above 30°C. 
- Do not freeze. 
- Keep the vial in the outer carton in order to protect from light.  
- Do not refrigerate the solution after preparation. 
- Use the reconstituted product within 3 hours to avoid the risk of microbial contamination 

because the product does not contain preservatives.  

- This medicine is for single use only. Discard any unused solution appropriately. 
- 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 VEYVONDI contains  

- The active substance is vonicog alfa (recombinant human von Willebrand factor). 
VEYVONDI 650 IU powder and solvent for solution for injection 

 Each vial of powder contains nominally 650 International Units (IU) vonicog alfa. 

After reconstitution with the 5 mL solvent provided, VEYVONDI contains approximately 

130 IU/mL vonicog alfa. 

 

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


34 

 

 

VEYVONDI 1300 IU powder and solvent for solution for injection 

Each vial of powder contains nominally 1300 International Units (IU) vonicog alfa. 

After reconstitution with the 10 mL solvent provided, VEYVONDI contains approximately 

130 IU/mL vonicog alfa. 

 

- The other ingredients are: 
Sodium citrate, glycine, trehalose dihydrate, mannitol, polysorbate 80 and water for injections. 

See section 2 “VEYVONDI contains sodium”. 

 

 

What VEYVONDI looks like and contents of the pack 

VEYVONDI is a white to off-white powder. After reconstitution, when drawn into the syringe, the 

solution is clear, colourless in appearance and free from flakes or other foreign particles. 

 

Each pack of VEYVONDI 650 IU contains: 

- powder in a glass vial with a rubber stopper 
- 5 mL of solvent in a glass vial with a rubber stopper 
- one reconstitution device (Mix2Vial) 
 

Each pack of VEYVONDI 1300 IU contains: 

- powder in a vial (type I glass), with a butyl rubber stopper 
- 10 mL of solvent in a vial (type I glass), with a rubber stopper (bromobutyl) 
- one reconstitution device (Mix2Vial) 
 

Marketing Authorisation Holder  

Baxalta Innovations GmbH 

Industriestraße 67 

1221 Vienna 

Austria 

Tel: +44(0)1256 894 959 

e-mail: medinfoEMEA@shire.com 

 

Manufacturer 

Baxter AG 

Industriestraße 67 

A-1221 Vienna 

Austria 

 

This leaflet was last revised in {month YYYY}. 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

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

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

Instructions for preparation and administration 

 

General instructions 

 

Check the expiry date, and ensure that the VEYVONDI powder and water for injections (solvent) are 

at room temperature prior to preparation. Do not use after the expiry date stated on the labels and 

carton. 

 

Use antiseptic technique (clean and low-germ conditions) and a flat work surface during the 

reconstitution procedure. Wash your hands and put on clean exam gloves (the use of gloves is 

optional). 

 



35 

 

 

Use the reconstituted product (after mixing the powder with the supplied water) as soon as possible 

and within three hours. You can store the reconstituted product at room temperature not to exceed 

25°C for up to three hours. Reconstituted product should not be refrigerated. Discard after three hours. 

 

Ensure that the VEYVONDI powder vial and the Sterilised Water for Injections (solvent) are at room 

temperature prior to preparation.  

 

Use plastic syringes with this product because proteins in the product tend to stick to the surface of 

glass syringes.  
Do not mix VEYVONDI with other medicinal products except for rFVIII. 

 

Instructions for reconstitution 

 

 Steps Image example 
1 Remove the caps from the VEYVONDI powder and solvent vials to 

expose the center of the rubber stoppers. 

 
2 Disinfect each stopper with a separate sterile alcohol swab (or other 

suitable sterile solution suggested by your doctor or haemophilia 

treatment center) by wiping the stopper for several seconds. Allow 

the rubber stoppers to dry. Place the vials on a flat surface. 

 

3 Open the Mix2Vial device package by completely peeling away the 

lid, without touching the inside of the package. Do not remove the 

Mix2Vial device from the package. 

NA 

4 Turn the package with the Mix2Vial device upside down and place it 

over the top of the solvent vial. Firmly insert the blue plastic spike of 

the device into the center of the solvent vial stopper by pushing 

straight down. Grip the package at its edge and lift it off the 

Mix2Vial device. Be careful not to touch the clear plastic spike. The 

solvent vial now has the Mix2Vial device connected to it and is 

ready to be connected to the VEYVONDI vial. 
 

5 To connect the solvent vial to the VEYVONDI vial, turn the solvent 

vial over and place it on top of the vial containing VEYVONDI 

concentrate. Fully insert the clear plastic spike into the VEYVONDI 

vial stopper by firmly pushing straight down. This should be done 

right away to keep the liquid free of germs. The solvent will flow 

into the VEYVONDI vial by vacuum. Check that all the solvent has 

transferred. Do not use if vacuum has been lost and the solvent does 

not flow into the VEYVONDI vial. 

 

6 Gently and continuously swirl the connected vials or allow the 

reconstituted product to stand for 5 minutes then gently swirl to 

ensure the powder is completely dissolved. Do not shake. Shaking 

will adversely affect the product. Do not refrigerate after 

reconstitution. 

 



36 

 

 

7 Disconnect the two sides of the Mix2Vial from each other by 

holding the clear plastic side of the Mix2Vial device attached to the 

VEYVONDI vial with one hand and the blue plastic side of the 

Mix2Vial device attached to the solvent vial with the other hand. 

Turn the blue plastic side counterclockwise and gently pull the two 

vials apart. Do not touch the end of the plastic connector attached to 

the VEYVONDI vial containing the dissolved product. Place the 

VEYVONDI vial on a flat work surface. Discard the empty solvent 

vial. 
 

8 Draw air into the empty, sterile disposable plastic syringe by pulling 

back on the plunger. The amount of air should equal the amount of 

reconstituted VEYVONDI that you will withdraw from the vial. 

 

9 Leaving the VEYVONDI vial (containing the dissolved product) on 

your flat work surface, connect the syringe to the clear plastic 

connector by attaching and turning the syringe clockwise. 

 

10 Hold the vial with one hand and use the other hand to all the air from 

the syringe into the vial 

 

11 Flip connected syringe and VEYVONDI vial so the vial is on top. 

Be sure to keep the syringe plunger pressed in. Draw the 

VEYVONDI into the syringe by pulling plunger back slowly. 

 

12 Do not push and pull solution back and forth between syringe and 

vial. Doing so may harm the medicine. When ready to infuse, 

disconnect the syringe by turning it counterclockwise. Inspect the 

syringe visually for particulate matter; the solution in the syringe 

should be clear. If flakes or particles are seen, do not use the solution 

and notify your doctor. 

 

13 If you need more than one vial of VEYVONDI to make up your  



37 

 

 

dose: 

• Leave the syringe attached to the vial until an additional 
vial is prepared.  

• Use the reconstitution steps above (2 to 8) to prepare the 
additional vial of VEYVONDI using a fresh Mix2Vial for 

each vial 

14 The contents of two vials may be drawn into a single syringe.  

NOTE: When pushing air into a second vial of VEYVONDI to be 

pooled into a syringe, position the vial and connected syringe so that 

the vial is on top. 

 

 

Instructions for administration 

Inspect the prepared solution in the syringe for particulate matter and discoloration prior to 

administration (the solution should be clear, colourless and free from particles). It is not uncommon 

for a few flakes or particles to remain in the product vial after reconstitution. The filter included in 

the Mix2Vial device removes those particles completely. Filtration does not influence dosage 

calculations. The solution in the syringe should not be used if it is cloudy or contains flakes or 

particles after filtration. 

 

1. Attach the infusion needle to a syringe containing VEYVONDI solution. For comfort, a 
winged (butterfly) infusion set is preferred. Point the needle up and remove any air bubbles by 

gently tapping the syringe with your finger and slowly and carefully pushing air out of the 

syringe and needle. 

2. Apply a tourniquet and get the infusion site ready by wiping the skin well with a sterile 
alcohol swab (or other suitable sterile solution suggested by your doctor or haemophilia 

treatment center). 

3. Insert the needle into the vein and remove the tourniquet. Slowly infuse VEYVONDI. Do not 
infuse any faster than 4 mL per minute. Disconnect the empty syringe. If your dose requires 

multiple syringes, attach and administer each additional syringe of VEYVONDI one at a time. 

Note:  

Do not remove butterfly needle until all syringes have been infused and do not touch the Luer 

port that connects to the syringe. 

If recombinant factor VIII has been prescribed, administer recombinant factor VIII within 

10 minutes after infusion of VEYVONDI has been completed. 

4. Take the needle out of the vein and use sterile gauze to put pressure on the infusion site for 
several minutes. 

 

In case large volumes of VEYVONDI are required, it is possible to pool two vials of VEYVONDI 

together. The contents of each reconstituted product of VEYVONDI can be drawn in a single syringe. 

However, in these cases the initially reconstituted solution should not be diluted any further.  

Do not recap the needle. Place the needle, syringe, and empty VEYVONDI and solvent vial(s) in a 

hard-walled sharps container for proper disposal. Do not dispose of these supplies in ordinary 

household trash. 



38 

 

 

 

 

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

 

The following information is intended for healthcare professionals only: 

 

Treatment of bleeding episodes (On-demand treatment) 

Dosage and frequency must be individualized based on clinical judgment, taking into account of 

severity of bleeding episode, site of bleeding, patient’s medical history, monitoring of appropriate 

clinical and laboratory measures (both VWF:RCo and FVIII:C levels). 

 

Start of treatment 

VEYVONDI should be administered with recombinant factor VIII if the FVIII:C levels are <40%, or 

are unknown, to control bleeding. The rFVIII dose should be calculated according to the difference 

between the patient’s baseline plasma FVIII:C level, and the desired peak FVIII:C level to achieve an 

appropriate plasma FVIII:C level based on the approximate mean recovery of 0.02 (IU/mL)/(IU/kg). 

The complete dose of VEYVONDI should be administered followed by rFVIII within 10 minutes. 

 

Calculating dose 

VEYVONDI dose [IU] = dose [IU/kg] x weight [kg] 

 

Subsequent infusions 

Administer a subsequent dose of 40 IU to 60 IU/kg of VEYVONDI infused every 8 to 24 hours as per 

the dosing ranges in Table 1, as long as clinically required. In major bleeding episodes, maintain 

trough levels of VWF:RCo greater than 50% for as long as deemed necessary. 

 

Table 1 

Dosing recommendations for the treatment of Minor and Major Haemorrhages 
 

Haemorrhage 
Initial Dose a 

(IU VWF:RCo/kg body weight) 

Subsequent Dose 

 

Minor 

(e.g. epistaxis, oral bleeding, 

menorrhagia) 

40 to 50 IU/kg 

40 to 50 IU/kg every 8 to 

24 hours (or as long as deemed 

clinically necessary) 

Major b 

(e.g. severe or refractory 

epistaxis, menorrhagia, 

Gastrointestinal bleeding, 

Central nervous system 

trauma, haemarthrosis, or 

traumatic haemorrhage) 

50 to 80 IU/kg 

40 to 60 IU/kg every 8 to 

24 hours for approximately 2-

3 days (or as long as deemed 

clinically necessary) 

aIf rFVIII is administered, see rFVIII package insert for reconstitution and administration instructions. 
bA bleed could be considered major if red blood cell transfusion is either required or potentially indicated or if 

bleeding occurs in a critical anatomical site (e.g., intracranial or gastrointestinal haemorrhage). 

 

Prevention of bleeding/haemorrhage and treatment in case of elective surgery 

Assess FVIII:C levels prior to initiation of any surgical procedure. The recommended minimum target 

levels are 0.4 IU/mL for minor and oral surgery and 0.8 IU/mL for major surgery. 

 

To ensure pre-operative endogenous FVIII levels of at least 0.4 IU/mL for minor and oral and 

0.8 IU/mL for major surgery, a dose of 40-60 IU/kg VEYVONDI may be administered 12-24 hours 

(pre-operative dose) prior to initiating elective surgery. Within 1 hour prior to surgery, patients should 



39 

 

 

receive a dose of VEYVONDI based on the assessment 3 hours before surgery. The dose depends on 

VWF and FVIII levels of the patient, the type and severity of the bleeding. 

 

If the FVIII:C levels are not at the recommended target, a dose of VEYVONDI alone should be 

administered within 1 hour prior to the procedure. If the FVIII:C levels are not at the recommended 

target levels, rFVIII should be administered in addition to vonicog alfa to raise VWF:RCo and 

FVIII:C. Please refer to (Table 2) for FVIII:C recommended target levels. 

 

Table 2 

VWF:RCo and FVIII:C Target Levels 

Recommended Target Peak Plasma Levels of VWF:RCo and FVIII:C to be Achieved Prior to 

Surgery for the Prevention of Excessive Bleeding During and After Surgery 

Type of 

Surgery 

VWF:RCo 

Target Peak 

Plasma Level 

FVIII:C Target 

Peak Plasma 

Level a 

Calculation of rVWF dose (to be 

administered within 1 hour prior to 

surgery) (IU VWF:RCo required) 

Minor 0.5-0.6 IU/mL 0.4 – 0.5 IU/mL ∆b VWF:RCo x BW (kg) /IR c 

Major 1 IU/mL 0.80 - 1 IU/mL ∆b VWF:RCo x BW (kg) /IR c 
a Additional rFVIII may be required to attain the recommended FVIII:C target peak plasma levels. Dosing 

guidance should be done based on the IR. 
b ∆ = Target peak plasma VWF:RCo – baseline plasma VWF:RCo 
cIR = Incremental Recovery as measured in the subject. If the IR is not available, assume an IR of 0.02 IU/mL 

per IU/kg. 

 

During and After Surgery 

 

After the initiation of the surgical procedure, the VWF:RCo and FVIII:C plasma levels should be 

monitored and the intra- and post-operative substitution regimen should be individualized according to 

the PK results, intensity and duration of the haemostatic challenge, and the institution’s standard of 

care. In general, the frequency of VEYVONDI dosing for post-operative substitution should range 

from twice a day to every 48 hours. Refer to Table 3 for treatment recommendations for subsequent 

maintenance doses. 

 

Table 3  

Recommended Target Trough Plasma Levels of VWF:RCo and FVIII:C and Minimum Duration 

of Treatment for Subsequent Maintenance Doses for the Prevention of Excessive Bleeding After 

Surgery 

Type of 

Surgery 

VWF:RCo 

Target Trough Plasma 

Level 

FVIII:C 

Target Trough Plasma 

Level 
Minimum 

Duration 

of 

treatment 

Frequency of 

dosing Up to 72 

hours post 

surgery 

After 

72 hours 

post 

surgery 

Up to 72 

hours post 

surgery 

After 

72 hours 

post 

surgery 

Minor ≥ 0.30 IU/mL - 
> 

0.40 IU/mL  
- 48 hours 

Every 12-24 hrs 

/ every other day 

Major > 0.50 IU/mL 
> 

0.30 IU/mL 

> 

0.50 IU/mL 

> 

0.40 IU/mL 
72 hours 

Every 12-24 hrs 

/ every other day 

 

Name and batch number of the medicinal product 

It is strongly recommended that every time that VEYVONDI 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. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURERS 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
	A. LABELLING
	B. PACKAGE LEAFLET