Vihuma

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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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 
 
Vihuma 250 IU powder and solvent for solution for injection. 
 
Vihuma 500 IU powder and solvent for solution for injection. 
 
Vihuma 1000 IU powder and solvent for solution for injection. 
 
Vihuma 2000 IU powder and solvent for solution for injection. 
 
Vihuma 2500 IU powder and solvent for solution for injection. 
 
Vihuma 3000 IU powder and solvent for solution for injection. 
 
Vihuma 4000 IU powder and solvent for solution for injection. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Vihuma 250 IU powder and solvent for solution for injection 
Each vial contains nominally 250 IU human coagulation factor VIII (rDNA), simoctocog alfa.  
Vihuma 250 IU contains approximately 100 IU/ml of human coagulation factor VIII (rDNA), 
simoctocog alfa after reconstitution. 
 
Vihuma 500 IU powder and solvent for solution for injection 
Each vial contains nominally 500 IU human coagulation factor VIII (rDNA), simoctocog alfa.  
Vihuma 500 IU contains approximately 200 IU/ml of human coagulation factor VIII (rDNA), 
simoctocog alfa after reconstitution. 
 
Vihuma 1000 IU powder and solvent for solution for injection 
Each vial contains nominally 1000 IU human coagulation factor VIII (rDNA), simoctocog alfa.  
Vihuma 1000 IU contains approximately 400 IU/ml of human coagulation factor VIII (rDNA), 
simoctocog alfa after reconstitution. 
 
Vihuma 2000 IU powder and solvent for solution for injection 
Each vial contains nominally 2000 IU human coagulation factor VIII (rDNA), simoctocog alfa.  
Vihuma 2000 IU contains approximately 800 IU/ml of human coagulation factor VIII (rDNA), 
simoctocog alfa after reconstitution. 
 
Vihuma 2500 IU powder and solvent for solution for injection 
Each vial contains nominally 2500 IU human coagulation factor VIII (rDNA), simoctocog alfa.  
Vihuma 2500 IU contains approximately 1000 IU/ml of human coagulation factor VIII (rDNA), 
simoctocog alfa after reconstitution. 
 
Vihuma 3000 IU powder and solvent for solution for injection 
Each vial contains nominally 3000 IU human coagulation factor VIII (rDNA), simoctocog alfa.  
Vihuma 3000 IU contains approximately 1200 IU/ml of human coagulation factor VIII (rDNA), 
simoctocog alfa after reconstitution. 
 
Vihuma 4000 IU powder and solvent for solution for injection 
Each vial contains nominally 4000 IU human coagulation factor VIII (rDNA), simoctocog alfa.  



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Vihuma 4000 IU contains approximately 1600 IU/ml of human coagulation factor VIII (rDNA), 
simoctocog alfa after reconstitution. 
 
The potency (IU) is determined using the European Pharmacopoeia chromogenic assay. The specific 
activity of Vihuma is approximately 9500 IU/mg protein. 
 
Simoctocog alfa (human coagulation factor VIII (rDNA)) is a purified protein that has 1440 amino 
acids. The amino acid sequence is comparable to the 90 + 80 kDa form of human plasma factor VIII 
(i.e. B-domain deleted). Vihuma is produced by recombinant DNA technology in genetically modified 
human embryonic kidney (HEK) 293F cells. No animal or human derived materials are added during 
the manufacturing process or to the final medicinal product. 
 
Excipient(s) with known effect 
7.35 mg sodium per ml reconstituted solution (18.4 mg sodium per vial). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection.  
 
Powder: white to off-white friable powder. 
 
Solvent: a clear, colourless liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII 
deficiency). 
Vihuma can be used for all age groups. 
 
4.2 Posology and method of administration 
 
Treatment should be under the supervision of a physician experienced in the treatment of haemophilia. 
 
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. 
 
When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining 
factor VIII activity in patients’ blood samples, plasma factor VIII activity results can be significantly 
affected by both the type of aPTT reagent and the reference standard used in the assay. Also there can 
be significant discrepancies between assay results obtained by aPTT-based one stage clotting assay 
and the chromogenic assay according to Ph. Eur. This is of importance particularly when changing the 
laboratory and/or reagents used in the assay. 
 
Posology 
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. 



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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). 
 
One International Unit (IU) of factor VIII activity is equivalent to the quantity of factor VIII in one 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 International Unit (IU) factor VIII per kg body weight raises the plasma factor VIII activity by 
approximately 2% of normal activity or 2 IU/dl. The required dose is determined using the following 
formula:  
 

Required units = body weight (kg) x desired factor VIII rise (%) (IU/dl) x 0.5 (IU/kg per IU/dl) 
 

Expected factor VIII rise (% of normal) =   2 x administered IU 
   body weight (kg) 

 
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, factor VIII activity should not fall below the given 
plasma activity level (in % of normal or IU/dl) in 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 (%) (IU/dL) 

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

Haemorrhage   

Early haemarthrosis, muscle 
bleeding or oral bleeding  

20–40 Repeat every 12 to 24 hours. 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 to 24 hours 
for 3 to 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 Every 24 hours, 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 therapy 
for at least another 7 days to maintain a 
factor VIII activity of 30% to 
60% (IU/dL).  

 
Prophylaxis 
For long-term prophylaxis against bleeding in patients with severe haemophilia A, the usual doses are 
20 to 40 IU of factor VIII per kg body weight at intervals of 2 to 3 days. The regimen may be adjusted 
based on patient response. 



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In some cases, especially in younger patients, shorter dosage intervals or higher doses may be 
necessary. 
 
Paediatric population 
The posology is the same in adults and children, however, shorter dose intervals or higher doses may 
be necessary for children. Currently available data are described in sections 4.8, 5.1 and 5.2. 
 
Method of administration 
Vihuma is for intravenous use. 
It is recommended that not more than 4 ml per minute be administered. 
 
For instructions on reconstitution of the medicinal product before administration, see section 6.6. 
 
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 
 
Hypersensitivity 
As with any intravenous protein product, allergic type hypersensitivity reactions are possible. Vihuma 
contains traces of human host cell proteins other than factor VIII. 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, standard medical treatment for shock should be implemented. 
 
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 the exposure to factor VIII, this risk being highest within the first 20 exposure 
days. Rarely, inhibitors may develop after the first 100 exposure days.  
 
Cases of recurrent inhibitor (low titre) have been observed after switching from one factor VIII 
product to another in previously treated patients with more than 100 exposure days who have a 
previous history of inhibitor development. Therefore, it is recommended to monitor all patients 
carefully for inhibitor occurrence following any product switch.  
 
The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titre 
inhibitors which are transiently present or remain consistently 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 factor VIII 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. 
 



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Catheter-related complications 
If a central venous access device (CVAD) is required, risk of CVAD-related complications including 
local infections, bacteraemia and catheter site thrombosis should be considered. 
 
It is strongly recommended that every time that Vihuma 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 medicinal product. 
 
Paediatric population 
The listed warnings and precautions apply both to adults and children. 
 
Excipient related considerations (sodium content) 
This medicinal product contains less than 1 mmol sodium (23 mg) per vial. 
However depending on the body weight and posology, the patient could receive more than one vial. 
This should be taken into consideration by patients on a controlled sodium diet. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed with Vihuma. 
 
4.6 Fertility, pregnancy and lactation 
 
Animal reproduction studies have not been conducted with Vihuma.  
Based on the rare occurrence of haemophilia A in women, experience regarding the use of factor VIII 
during pregnancy and breast feeding is not available. Therefore, Vihuma should be used during 
pregnancy and breast-feeding only if clearly indicated. There are no fertility data available. 
 
4.7 Effects on ability to drive and use machines 
 
Vihuma has no influence on the ability to drive and use machines.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
Hypersensitivity or allergic reactions (which may include angiooedema, burning and stinging at the 
infusion site, chills, flushing, headache, hives, hypotension, lethargy, nausea, rash, restlessness, 
tachycardia, tightness of the chest, tingling, urticaria, including generalised urticaria, vomiting, 
wheezing) have rarely been observed with FVIII preparations and may in some cases progress to 
severe anaphylaxis (including shock).  
 
Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated 
with factor VIII, including with Vihuma. If such inhibitors occur, the condition will manifest itself as 
an insufficient clinical response. In such cases, it is recommended that a specialised haemophilia 
centre be contacted. 
 
Tabulated list of adverse reactions 
During clinical studies with Vihuma in previously treated paediatric (2 to 11 years, n = 58), adolescent 
(12 to 17 years, n = 3) and adult patients (n = 129) with severe haemophilia A, a total of 12 adverse 
drug reactions (ADRs) (8 in adults, 4 in children) were reported in 8 patients (4 adults, 4 children).  
 
Table 1 presented below is according to the MedDRA system organ classification (SOC and Preferred 
Term Level). 
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). 
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 



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Table 1. Frequency of adverse drug reactions (ADRs) in clinical trials 

MedDRA Standard System 
Organ Class 

Adverse reactions Frequency 

Blood and lymphatic system 
disorders 

Haemorrhagic anaemia 
Factor VIII inhibition 

Uncommon* 
Uncommon (PTPs) # 
Very common (PUPs)# 

Immune system disorders Hypersensitivity Common* 
Nervous system disorders Paraesthesia 

Headache 
Dizziness 

Uncommon* 
Uncommon* 
Uncommon* 

Ear and labyrinth disorders Vertigo Uncommon* 
Gastrointestinal disorders Dry mouth Uncommon* 
Musculoskeletal and connective 
tissue disorders 

Back pain Uncommon* 

General disorders and 
administration site conditions 

Pyrexia 
Injection site inflammation 
Injection site pain 
Malaise 

Common* 
Uncommon* 
Uncommon* 
Uncommon* 

Investigations Non-neutralising antibody 
positive (in PTPs) 

Uncommon* 

Respiratory, thoracic and 
mediastinal disorders 

Dyspnoea Uncommon* 

* Calculated as patients with ADR per total number of 280 trial patients, of which 190 previously treated patients 
(PTPs) and 90 previously untreated patients (PUPs). 
#  Frequency is based on studies with all FVIII products which included patients with severe haemophilia A. PTPs 
= previously-treated patients, PUPs = previously-untreated patients 
 
Description of selected adverse reactions 
A non-neutralizing anti-Factor VIII antibody was detected in one adult patient (see Table 1). The sample 
was tested by the central laboratory at eight dilutions. The result was positive only at dilution factor 1 
and the antibody titre was very low. Inhibitory activity, as measured by the modified Bethesda assay, 
was not detected in this patient. Clinical efficacy and in-vivo recovery of Vihuma was not affected in 
this patient. 
 
Paediatric population 
Frequency, type and severity of adverse reactions in children are assumed to be the same as in adults. 
 
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 cases of overdose have been reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antihaemorrhagics: blood coagulation factor VIII, ATC code: B02BD02. 
 
The factor VIII/von Willebrand factor complex consists of two molecules (factor VIII and von 
Willebrand factor) with different physiological functions. When infused into a haemophiliac patient, 

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000134.jsp&mid=WC0b01ac0580022c59


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factor VIII binds to von Willebrand factor in the patient’s circulation. Activated factor VIII 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 factor VIII:C and results in profuse bleeding into joints, muscles or internal 
organs, either spontaneously or as results of accidental or surgical trauma. By replacement therapy the 
plasma levels of factor VIII are increased, thereby temporarily enabling a correction of the factor VIII 
deficiency and correction of the bleeding tendencies. 
 
The immunogenicity of Vihuma was evaluated in clinical trials in 190 previously treated patients with 
severe haemophilia A (129 adult and 61 paediatric patients). None of the patients developed inhibitors. 
 
Adult and adolescent population 12 - 65 years of age 
 
Prophylaxis: In a clinical study in 32 adult patients with severe haemophilia A, the median 
consumption of Vihuma for prophylaxis was 468.7 IU/kg/month. 
 
Treatment of bleeding: The median dose to treat break-through bleeding episodes was 33.0 IU/kg in 
these patients who were on prophylaxis. In another clinical study, 22 adult patients were treated on 
demand.  In total 986 bleeding episodes were treated with a median dose of 30.9 IU/kg. In general, 
minor bleeds required slightly lower, and more severe bleeds required up to three-fold higher median 
doses. 
 
Individualised prophylaxis: Individualised PK-based prophylaxis was evaluated in 66 adult PTPs with 
severe haemophilia A. Following a 1-3 month standard prophylaxis phase (every other day or 3 times 
weekly dosing), 44 (67%) patients were switched to a dosing regimen based on their PK assessment, 
and 40 completed the 6 months of prophylaxis according to the assigned dosing and treatment scheme. 
Of these patients, 34 (85%) were treated twice weekly or less. 33 (82.5%) patients did not experience 
any bleeds and 36 (90.0%) patients had no spontaneous bleeds. The mean ± SD annualised bleeding 
rate was 1.2 ± 3.9 and the mean ± SD dose were 52.2 ± 12.2 IU/kg per injection and 99.7 ± 25.6 
IU/kg per week. 
Of note, annualised bleeding rate (ABR) is not comparable between different factor concentrates and 
between different clinical studies. 
 
Paediatric population 
Data have been obtained in 29 previously treated children between 2 and 5 years of age, 31 children 
between 6 and 12 years of age and one adolescent of 14 years. The median dose per prophylactic 
infusion was 37.8 IU/kg. Twenty patients used median doses of more than 45 IU/kg. The median 
consumption of Vihuma for prophylaxis per month was 521.9 IU/kg. A higher median dose of Vihuma 
was required to treat bleedings in children (43.9 IU/kg) than in adults (33.0 IU/kg), and a higher 
median dose was required to treat moderate to major than minor bleedings (78.2 IU/kg vs. 41.7 IU/kg). 
Younger children in general required higher median doses (6-12 years: 43.9 IU/kg; 2-5 years: 
52.6 IU/kg). These data were corroborated by a long-term follow-up of 49 of these children who were 
treated for an additional median period of approximately 30 months (range from 9.5 to 52 months); 
during this period 45% of children had no spontaneous bleeds 
 
A prospective open-label clinical study in PUPs with severe haemophilia A (<1% FVIII:C) is ongoing. 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Vihuma in one or more subsets of the paediatric population in treatment of haemophilia A (congenital 
Factor VIII deficiency) (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Adult population  
 



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Table 2. PK parameters for Vihuma (Dose: 50 IU/kg) in adult previously treated patients (age 
18-65 years) with severe haemophilia A (n = 20) 

PK parameter Chromogenic assay 
Mean ± SD Median (range) 

AUC (hr*IU/ml) 22.6 ± 8.0 22.3 (8.4 – 38.1) 
T1/2 (hr) 14.7 ± 10.4 12.5 (5.4 – 55.6) 
IVR (%/IU/kg) 2.5 ± 0.4 2.5 (1.7 – 3.2) 
CL (ml/hr/kg) 3.0 ± 1.2 2.7 (1.5-6.4) 

AUC = Area under the curve (FVIII:C), T1/2 = Terminal half-life,  
IVR = Incremental in vivo recovery, CL = Clearance, SD = Standard deviation  
 
 
Table 3. PK parameters for Vihuma (Dose: 50 IU/kg) in previously treated children aged 6 to 12 
years with severe haemophilia A (n = 12) 

PK parameter Chromogenic assay 
Mean ± SD Median (range) 

AUC (hr*IU/ml) 13.2 ± 3.4 12.8 (7.8 – 19.1) 
T1/2 (hr) 10.0 ± 1.9 9.9 (7.6 – 14.1) 
IVR (%/IU/kg) 1.9 ± 0.4 1.9 (1.2 – 2.6) 
CL (ml/hr/kg) 4.3 ± 1.2  4.2 (2.8 - 6.9)  

AUC = Area under the curve (FVIII:C), T1/2 = Terminal half-life,  
IVR = Incremental in vivo recovery, CL = Clearance, SD = Standard deviation 
 
 
Table 4. PK parameters for Vihuma (Dose: 50 IU/kg) in previously treated children aged 2 to 5 
years with severe haemophilia A (n = 13) 

PK parameter Chromogenic assay 
Mean ± SD Median (range) 

AUC (hr*IU/ml) 11.7 ± 5.3  10.5 (4.9 – 23.8)  
T1/2 (hr) 9.5 ± 3.3 8.2 (4.3 – 17.3) 
IVR (%/IU/kg) 1.9 ± 0.3 1.8 (1.5 – 2.4) 
CL (ml/hr/kg) 5.4 ± 2.4 5.1 ( 2.3 – 10.9) 

AUC = Area under the curve (FVIII:C), T1/2 = Terminal half-life, 
IVR = Incremental in vivo recovery, CL = Clearance, SD = Standard deviation 
 
Paediatric population 
As known from the literature, recovery and half-life was lower in young children than in adults and 
clearance higher, which may be due in part to the known higher plasma volume per kilogram body 
weight in younger patients.  
 
Weight adjusted subgroups 
 
Table 5. Weight-adjusted PK parameters for Vihuma (Dose: 50 IU/kg) in adult previously 
treated patients (age 18-65 years) with severe haemophilia A (n = 20)  

PK parameter All (n=20) 
Normal weight 

(n=14) 
Pre-adipose 

(n=4) 
Adipose 

(n=2) 
 Chromogenic assay Mean ± SD 

AUC (hr*IU/ml) 22.6 ± 8.0  20.4 ± 6.9  24.9 ± 8.9 33.5 ± 6.5 
T1/2 (hr) 14.7 ± 10.4 14.7 ± 12.1 13.4 ± 5.9 17.2 ± 4.8 
IVR (%/IU/kg) 2.5 ± 0.4 2.4 ± 0.4 2.7 ± 0.4 2.8 ± 0.3 
CL (ml/hr/kg) 3.0 ± 1.2  3.2 ± 1.3 2.6 ± 1.0 1.8 ± 0.4 
 Chromogenic assay Median (range) 
AUC (hr*IU/ml) 22.3 (8.4 – 38.1)  21.2 (8.4 – 32.6)  23.3 (17.4 – 35.5) 33.5 (28.9 – 38.1) 
T1/2 (hr) 12.5 (5.4 – 55.6) 12.3 (5.4 – 55.6) 11.2 (9.3 – 22.0) 17.2 (13.8 – 20.6) 
IVR (%/IU/kg) 2.5 (1.7 – 3.2) 2.4 (1.7 – 3.1) 2.8 (2.3 – 3.2) 2.8 (2.6 – 3.0) 
CL (ml/hr/kg) 2.7 (1.5 – 6.4)  2.8 (1.7 – 6.4) 2.5 (1.6 – 3.7) 1.8 (1.5 – 2.0) 



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Normal weight: BMI 18.5-25 kg/m2, Pre-adipose: BMI 25-30 kg/m2, Adipose: BMI > 30 kg/m2, SD = 
Standard deviation 
 
5.3 Preclinical safety data 
 
In preclinical studies, Vihuma was used to safely and effectively restore haemostasis in dogs with 
haemophilia. Toxicology studies showed that local intravenous administration and systemic exposure 
were well tolerated in laboratory animals (rats and cynomolgus monkeys). 
 
Specific studies with long-term repeated administration such as reproduction toxicity, chronic toxicity, 
and carcinogenicity were not performed with Vihuma due to the immune response to heterologous 
proteins in all non-human mammalian species. 
 
No studies were performed on the mutagenic potential of Vihuma.  
Ex vivo evaluations using a commercial assay kit to quantify T cell response to protein therapeutics 
indicate a low risk of immunogenicity. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder 
Sucrose 
Sodium chloride 
Calcium chloride dihydrate 
Arginine hydrochloride 
Sodium citrate dihydrate 
Poloxamer 188 
 
Solvent 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
Only the provided injection sets should be used because treatment failure can occur as a consequence 
of human coagulation factor VIII adsorption to the internal surfaces of some injection equipment. 
 
6.3 Shelf life 
 
Unopened vial 
2 years 
 
During the shelf-life, the product may be kept at room temperature (up to 25°C) for a single period not 
exceeding 1 month. Once the product has been taken out of the refrigerator the product must not be 
returned to the refrigerator. Please record the beginning of storage at room temperature on the product 
carton. Keep the vial in the outer carton in order to protect from light. 
 
After reconstitution 
After reconstitution, chemical and physical in-use stability has been demonstrated for 24 hours when 
stored at room temperature. 
 



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From a microbiological point of view, the product should be used immediately after reconstitution. If 
not used immediately, in-use storage times and conditions prior to use are the responsibility of the 
user. 
Keep the reconstituted solution at room temperature. Do not refrigerate after reconstitution. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C).  
Do not freeze.  
Keep the vial in the outer carton in order to protect from light.  
 
For storage at room temperature and storage conditions after reconstitution of the medicinal product, 
see section 6.3. 
 
6.5 Nature and contents of container  
 
Each pack contains: 

- 1 powder vial with 250, 500, 1000, 2000, 2500, 3000 or 4000 IU simoctocog alfa in a type 1 
glass vial, closed with coated bromobutyl stopper and sealed with aluminium flip-off cap 

- Solvent: 2.5 ml water for injections in a pre-filled borosilicate glass syringe  
- 1 sterile vial adapter for reconstitution with 1 butterfly needle and 2 alcohol swabs  

 
 
6.6 Special precautions for disposal and other handling 
 
The powder should only be reconstituted with the supplied solvent (2.5 ml water for injections) using 
the supplied injection set. The vial should be gently rotated until all powder is dissolved. After 
reconstitution, the solution should be drawn back into the syringe.  
 
The reconstituted medicinal product should be inspected visually for particulate matter and 
discoloration prior to administration. The reconstituted medicinal product is a clear, colourless 
solution, free from foreign particles and has a pH of 6.5 to 7.5.  Do not use solutions that are cloudy or 
have deposits. 
 
Instructions for preparation and administration 
 

1. Allow the solvent syringe (water for injections) and the powder in the closed vial to reach 
room temperature. You can do this by holding them in your hands until they feel as warm as 
your hands. Do not use any other way to heat the vial and pre-filled syringe. This temperature 
should be maintained during reconstitution. 

2. Remove the plastic flip-top cap from the powder vial to expose the central portions of the 
rubber stopper. Do not remove the gray stopper or metal ring around the top of the vial.  



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3. Wipe the top of the vial with an alcohol swab. Allow the alcohol to dry.  
4. Peel back the paper cover from the vial adapter package. Do not remove the adapter from the 

package.  

  
5. Place the powder vial on an even surface and hold it. Take the adapter package and place the 

vial adapter over the centre of the rubber stopper of the powder vial. Press down firmly the 
adapter package until the adapter spike penetrates the rubber stopper. The adapter snaps to the 
vial when done. 

 
6. Peel back the paper cover from the pre-filled syringe package. Hold the plunger rod at the end 

and do not touch the shaft. Attach the threaded end of the plunger rod to the solvent syringe 
plunger. Turn the plunger rod clockwise until a slight resistance is felt. 



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7. Break off the tamper-proof plastic tip from the solvent syringe by snapping the perforation of 

the cap. Do not touch the inside of the cap or the syringe tip. In case the solution is not used 
immediately close the filled syringe with the tamper-proof plastic tip for storage. 

 
8. Remove the adapter packaging and discard. 
9. Firmly connect the solvent syringe to the vial adapter by turning clockwise until resistance is 

felt. 

 
10. Slowly inject all solvent into the powder vial by pressing down the plunger rod. 



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11. Without removing the syringe, gently move or swirl the vial in circles a few times to dissolve 

the powder. Do not shake. Wait until all the powder dissolves completely. 
12. Visually inspect the final solution for particles before administration. The solution should be 

clear and colourless, practically free from visible particles. Do not use solutions that are 
cloudy or have deposits. 

13. Turn the vial attached to the syringe upside down, and slowly draw the final solution into the 
syringe. Make sure that the entire content of the vial is transferred to the syringe.  

 
14. Detach the filled syringe from the vial adapter by turning counter clockwise and discard the 

empty vial. 
15. The solution is now prepared for immediate use. Do not refrigerate. 
16. Clean the chosen injection site with one of the provided alcohol swabs. 
17. Attach the provided infusion set to the syringe. 

Insert the needle of the infusion set into the chosen vein. If you have used a tourniquet to make 
the vein easier to see, this tourniquet should be released before you start injecting the solution. 
No blood must flow into the syringe due to the risk of formation of fibrin clots. 

18. Inject the solution into the vein at a slow speed, not faster than 4 ml per minute. 
 
If you use more than one vial of powder for one treatment, you may use the same injection needle 
again. The vial adapter and the syringe are for single use only. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 



15 

Octapharma AB 
Lars Forssells gata 23 
112 75 Stockholm 
Sweden 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1168/001 
EU/1/16/1168/002 
EU/1/16/1168/003 
EU/1/16/1168/004 
EU/1/16/1168/005 
EU/1/16/1168/006 
EU/1/16/1168/007 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 13 February 2017 
 
 
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 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. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

Name and address of the manufacturer(s) of the biological active substance 

Octapharma AB 
Lars Forssells gata 23 
112 75 Stockholm 
SWEDEN 
 
Name and address of the manufacturer(s) responsible for batch release 

Octapharma AB 
Lars Forssells gata 23 
112 75 Stockholm 
SWEDEN 
 

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  
 

The requirements for submission of periodic safety update reports 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 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; 

• 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.  

  



18 

 
 
 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 

 
LABELLING AND PACKAGE LEAFLET 

 
  



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 

  



20 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vihuma 250 International Units powder and solvent for solution for injection 
 
simoctocog alfa (recombinant human coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 Powder vial contains 250 International Units simoctocog alfa (100 IU/ml after reconstitution). 
  
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium 
citrate dihydrate, poloxamer 188 
Solvent: Water for injections 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection 
 
1 Powder vial, 1 pre-filled syringe, 1 vial adapter, 1 butterfly needle, 2 alcohol swabs 
1 Pre-filled syringe contains 2.5 ml water for injections. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after reconstitution. 
 
 
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 
 



21 

Store in a refrigerator. Do not freeze. Store in the original package in order to protect from light.  
Can be stored at room temperature (up to 25°C) for a single period up to 1 month. 
Taken out of refrigerator: _____________  
 
 
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 
 
Octapharma AB 
Lars Forssells gata 23 
112 75 Stockholm 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1168/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Vihuma 250 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



22 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Vihuma 250 International Units powder for solution for injection 
simoctocog alfa (recombinant human coagulation factor VIII). 
For intravenous use after reconstitution. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
250 IU/vial  
 
 
6. OTHER 
 
 
 
  



23 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vihuma 500 International Units powder and solvent for solution for injection 
 
simoctocog alfa (recombinant human coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 Powder vial contains 500 International Units simoctocog alfa (200 IU/ml after reconstitution). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium 
citrate dihydrate, poloxamer 188 
Solvent: Water for injections 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection 
 
1 Powder vial, 1 pre-filled syringe, 1 vial adapter, 1 butterfly needle, 2 alcohol swabs 
1 Pre-filled syringe contains 2.5 ml water for injections. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after reconstitution. 
 
 
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 
 



24 

Store in a refrigerator. Do not freeze. Store in the original package in order to protect from light.  
Can be stored at room temperature (up to 25°C) for a single period up to 1 month. 
Taken out of refrigerator: _____________  
 
 
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 
 
Octapharma AB 
Lars Forssells gata 23 
112 75 Stockholm 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1168/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Vihuma 500 
 
 
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 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Vihuma 500 International Units powder for solution for injection 
simoctocog alfa (recombinant human coagulation factor VIII). 
For intravenous use after reconstitution. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
500 IU/vial  
 
 
6. OTHER 
 
 
 
  



26 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vihuma 1000 International Units powder and solvent for solution for injection 
 
simoctocog alfa (recombinant human coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 Powder vial contains 1000 International Units simoctocog alfa (400 IU/ml after reconstitution). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium 
citrate dihydrate, poloxamer 188 
Solvent: Water for injections 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection 
 
1 Powder vial, 1 pre-filled syringe, 1 vial adapter, 1 butterfly needle, 2 alcohol swabs 
1 Pre-filled syringe contains 2.5 ml water for injections. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after reconstitution. 
 
 
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 
 



27 

Store in a refrigerator. Do not freeze. Store in the original package in order to protect from light.  
Can be stored at room temperature (up to 25°C) for a single period up to 1 month. 
Taken out of refrigerator: _____________  
 
 
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 
 
Octapharma AB 
Lars Forssells gata 23 
112 75 Stockholm 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1168/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Vihuma 1000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



28 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Vihuma 1000 International Units powder for solution for injection 
simoctocog alfa (recombinant human coagulation factor VIII). 
For intravenous use after reconstitution. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1000 IU/vial  
 
 
6. OTHER 
 
 
 
  



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vihuma 2000 International Units powder and solvent for solution for injection 
 
simoctocog alfa (recombinant human coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 Powder vial contains 2000 International Units simoctocog alfa (800 IU/ml after reconstitution). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium 
citrate dihydrate, poloxamer 188 
Solvent: Water for injections 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection 
 
1 Powder vial, 1 pre-filled syringe, 1 vial adapter, 1 butterfly needle, 2 alcohol swabs 
1 Pre-filled syringe contains 2.5 ml water for injections. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after reconstitution. 
 
 
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 
 



30 

Store in a refrigerator. Do not freeze. Store in the original package in order to protect from light.  
Can be stored at room temperature (up to 25°C) for a single period up to 1 month. 
Taken out of refrigerator: _____________  
 
 
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 
 
Octapharma AB 
Lars Forssells gata 23 
112 75 Stockholm 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1168/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Vihuma 2000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



31 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Vihuma 2000 International Units powder for solution for injection 
simoctocog alfa (recombinant human coagulation factor VIII). 
For intravenous use after reconstitution. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2000 IU/vial  
 
 
6. OTHER 
 
 
 



32 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vihuma 2500 International Units powder and solvent for solution for injection 
 
simoctocog alfa (recombinant human coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 Powder vial contains 2500 International Units simoctocog alfa (1000 IU/ml after reconstitution). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium 
citrate dihydrate, poloxamer 188 
Solvent: Water for injections 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection 
 
1 Powder vial, 1 pre-filled syringe, 1 vial adapter, 1 butterfly needle, 2 alcohol swabs 
1 Pre-filled syringe contains 2.5 ml water for injections. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after reconstitution. 
 
 
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 
 



33 

Store in a refrigerator. Do not freeze. Store in the original package in order to protect from light.  
Can be stored at room temperature (up to 25°C) for a single period up to 1 month. 
Taken out of refrigerator: _____________  
 
 
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 
 
Octapharma AB 
Lars Forssells gata 23 
112 75 Stockholm 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1168/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Vihuma 2500 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



34 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Vihuma 2500 International Units powder for solution for injection 
simoctocog alfa (recombinant human coagulation factor VIII). 
For intravenous use after reconstitution. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2500 IU/vial  
 
 
6. OTHER 
 
 
 
 
 



35 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vihuma 3000 International Units powder and solvent for solution for injection 
 
simoctocog alfa (recombinant human coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 Powder vial contains 3000 International Units simoctocog alfa (1200 IU/ml after reconstitution). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium 
citrate dihydrate, poloxamer 188 
Solvent: Water for injections 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection 
 
1 Powder vial, 1 pre-filled syringe, 1 vial adapter, 1 butterfly needle, 2 alcohol swabs 
1 Pre-filled syringe contains 2.5 ml water for injections. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after reconstitution. 
 
 
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 
 



36 

Store in a refrigerator. Do not freeze. Store in the original package in order to protect from light.  
Can be stored at room temperature (up to 25°C) for a single period up to 1 month. 
Taken out of refrigerator: _____________  
 
 
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 
 
Octapharma AB 
Lars Forssells gata 23 
112 75 Stockholm 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1168/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Vihuma 3000 
 
 
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 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Vihuma 3000 International Units powder for solution for injection 
simoctocog alfa (recombinant human coagulation factor VIII). 
For intravenous use after reconstitution. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3000 IU/vial  
 
 
6. OTHER 
 
 
 
 



38 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Vihuma 4000 International Units powder and solvent for solution for injection 
 
simoctocog alfa (recombinant human coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 Powder vial contains 4000 International Units simoctocog alfa (16000 IU/ml after reconstitution). 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium 
citrate dihydrate, poloxamer 188 
Solvent: Water for injections 
See package leaflet for further information. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection 
 
1 Powder vial, 1 pre-filled syringe, 1 vial adapter, 1 butterfly needle, 2 alcohol swabs 
1 Pre-filled syringe contains 2.5 ml water for injections. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous use after reconstitution. 
 
 
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 
 



39 

Store in a refrigerator. Do not freeze. Store in the original package in order to protect from light.  
Can be stored at room temperature (up to 25°C) for a single period up to 1 month. 
Taken out of refrigerator: _____________  
 
 
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 
 
Octapharma AB 
Lars Forssells gata 23 
112 75 Stockholm 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1168/007 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Vihuma 4000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



40 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Vihuma 4000 International Units powder for solution for injection 
simoctocog alfa (recombinant human coagulation factor VIII). 
For intravenous use after reconstitution. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
4000 IU/vial  
 
 
6. OTHER 
 
 
 
  



41 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE WITH 2.5 ML WATER FOR INJECTIONS 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Vihuma 
Water for injections 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2.5 ml 
 
 
6. OTHER 
 
 
  



42 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



43 

Package leaflet: Information for the user 
 

Vihuma 250 IU powder and solvent for solution for injection 
Vihuma 500 IU powder and solvent for solution for injection 
Vihuma 1000 IU powder and solvent for solution for injection 
Vihuma 2000 IU powder and solvent for solution for injection 
Vihuma 2500 IU powder and solvent for solution for injection 
Vihuma 3000 IU powder and solvent for solution for injection 
Vihuma 4000 IU powder and solvent for solution for injection 

simoctocog alfa (recombinant human coagulation factor VIII) 
 

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 or pharmacist. 
- 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 or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Vihuma is and what it is used for  
2. What you need to know before you use Vihuma 
3. How to use Vihuma 
4. Possible side effects  
5. How to store Vihuma  
6. Contents of the pack and other information 
 
 
1. What Vihuma is and what it is used for 
 
Vihuma contains the active substance human recombinant coagulation factor VIII (simoctocog alfa). 
Factor VIII is necessary for the blood to form clots and stop bleeding. In patients with haemophilia A 
(inborn factor VIII deficiency), factor VIII is missing or not working properly. 
Vihuma replaces the missing factor VIII and is used for treatment and prevention of bleeding in patients 
with haemophilia A and can be used for all age groups.  
 
 
2. What you need to know before you use Vihuma 
 
Do not use Vihuma: 

• if you are allergic to the active substance simoctocog alfa or any of the other ingredients of 
this medicine (listed in section 6). 

If you are unsure about this, ask your doctor. 
 
Warnings and precautions  
Talk to your doctor or pharmacist before using Vihuma. 
 
There is a rare chance that you may experience an anaphylactic reaction (a severe, sudden allergic 
reaction) to Vihuma. You should be aware of the early signs of allergic reactions as they are listed in 
section 4 “Allergic reactions”.  
If any of these symptoms occur, stop the injection immediately and contact your doctor. 



44 

 
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 
you or your child´s bleeding is not being controlled with Vihuma, tell your doctor immediately. 
 
Cardiovascular events  
In patients with existing cardiovascular risk factors, substitution therapy with FVIII may increase the 
cardiovascular risk. 
 
Catheter-related complications 
If you require a central venous access device (CVAD), risk of CVAD-related complications including 
local infections, presence of bacteria in the blood and catheter site thrombosis should be considered. 
 
It is strongly recommended that every time that Vihuma is administered, the name and batch number 
of the product are recorded in order to maintain a link between you and the batch of the medicinal 
product. 
 
 
Other medicines and Vihuma 
Tell your doctor or pharmacist 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 using this medicine.  
 
Driving and using machines 
Vihuma has no influence on your ability to drive and use machines.  
 
Vihuma contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per vial. 
However depending on your body weight and your dose of Vihuma, you could receive more than one 
vial. This should be taken into consideration if you are on a controlled sodium diet. 
 
 
3. How to use Vihuma 
 
Treatment with Vihuma will be started by a doctor who is experienced in the care of patients with 
haemophilia A. Always use this medicine exactly as your doctor or nurse has told you. Check with 
your doctor or nurse if you are not sure. 
 
Vihuma is usually injected into a vein (intravenously) by your doctor or a nurse who are experienced 
in the care of patients with haemophilia A. You or someone else might also give your Vihuma 
injection, but only after receiving adequate training. 
 
Your doctor will calculate your dose of Vihuma (in international units = IU) depending on your 
condition and body weight, and on whether it is used for prevention or treatment of bleeding. How 
often you need an injection will depend on how well Vihuma is working for you. Usually, treatment 
for haemophilia A is a life-long treatment. 
 
Prevention of bleeding 
The usual dose of Vihuma is 20 to 40 IU per kg body weight, given every 2 to 3 days. However, in 
some cases, especially in younger patients, more frequent injections or higher doses may be necessary. 
 
Treatment of bleeding 
The dose of Vihuma is calculated depending on your body weight and the factor VIII levels to be 
achieved. The target factor VIII levels will depend on the severity and location of the bleeding.  



45 

 
If you have the impression that the effect of Vihuma is insufficient, talk to your doctor. Your doctor 
will perform appropriate laboratory tests to make sure that you have adequate factor VIII levels. This 
is particularly important if you are having major surgery. 
 
Patients developing factor VIII inhibitors 
If your plasma factor VIII fails to reach expected levels with Vihuma, or if bleeding is not adequately 
controlled, it could be due to the development of factor VIII inhibitors. This will be checked by your 
doctor. You might need a higher dose of Vihuma or a different product to control bleedings. Do not 
increase the total dose of Vihuma to control your bleeding without consulting your doctor. 
 
Use in children 
The way Vihuma is used in children does not differ from the way it is used in adults. Because factor 
VIII products may have to be given more often in children, a central venous access device (CVAD, an 
external connector allowing access to the bloodstream through a catheter without injection through the 
skin) may need to be fitted. 
 
If you use more Vihuma than you should 
No symptoms of overdose have been reported. If you have injected more Vihuma than you should, 
please inform your doctor. 
 
If you forget to use Vihuma 
Do not take a double dose to make up for a forgotten dose. Proceed with the next dose immediately 
and continue as advised by your doctor or pharmacist. 
 
If you stop using Vihuma 
Do not stop using Vihuma without consulting your doctor or pharmacist. 
 
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 can cause side effects, although not everybody gets them. 
 
Allergic reactions 
You should be aware of the early signs of allergic reactions. If severe, sudden allergic reactions 
(anaphylactic) occur (very rare, up to 1 in 10,000), the injection must be stopped immediately. You 
must contact your doctor immediately if you notice any of the following symptoms: 
 
- rash, hives, wheals, generalised itching, 
- swelling of lips and tongue, 
- difficulty in breathing, wheezing, tightness in the chest, 
- general feeling of being unwell, 
- dizziness and loss of consciousness. 
 
These symptoms can be early symptoms of an anaphylactic shock.  If any of these symptoms occur, 
stop the injection immediately and contact your doctor. Severe symptoms require prompt emergency 
treatment. 
 
Uncommon side effects may affect up to 1 in 100 people 
Tingling or numbness (paraesthesia), headache, injection site inflammation, injection site pain, back 
pain, vertigo, dry mouth, dizziness, a vague feeling of bodily discomfort, shortness of breath.  
 
Common side effects may affect up to 1 in 10 people 
Hypersensitivity, fever. 
 



46 

Very common side effects may affect more than 1 in 10 people 
Factor VIII inhibitors in previously untreated patients. 
 
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 you or your child´s medicines may stop working properly and you or your 
child may experience persistent bleeding. If this happens, you should contact your doctor immediately. 
 
Side effects related to central venous access devices (CVAD): 
Catheter-related infection, general (systemic) infection and local blood clot at the catheter site. 
 
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 Vihuma 
 
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. 
 
Store in a refrigerator (2°C – 8°C). Do not freeze. Keep the vial in the outer carton in order to protect 
from light. 
 
Before the Vihuma powder is reconstituted it may be kept at room temperature (up to 25°C) for a single 
period not exceeding 1 month. Please record the date from when you start to store Vihuma at room 
temperature on the product carton. Do not store Vihuma in the refrigerator again after it has been stored 
at room temperature. 
Use the reconstituted solution immediately after reconstitution. 
 
Do not use the product in case you notice visible signs of deterioration of the tamper proof of 
packaging especially of the syringe and/or the vial. 
 
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 Vihuma contains 
Powder: 
- The active substance is recombinant human coagulation factor VIII (simoctocog alfa).  

Each powder vial contains 250, 500, 1000, 2000, 2500, 3000 or 4000 IU of simoctocog alfa. 
- The other ingredients are sucrose, sodium chloride, calcium chloride dihydrate, arginine 

hydrochloride, sodium citrate dihydrate and poloxamer 188. See section 2, “Vihuma contains 
sodium”. 

 
Solvent: 
Water for injections 
 
What Vihuma looks like and contents of the pack 
Vihuma is provided as powder and solvent for solution for injection. The powder is a white to off-
white friable powder in a glass vial. The solvent is water for injections in a pre-filled glass syringe. 

http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000134.jsp&mid=WC0b01ac0580022c59


47 

After reconstitution, the solution is clear, colourless and free from foreign particles. 
 
 
Each pack of Vihuma contains: 
- 1 powder vial with 250, 500, 1000, 2000, 2500, 3000 or 4000 IU simoctocog alfa 
- 1 pre-filled syringe with 2.5 ml water for injections 
- 1 vial adapter 
- 1 butterfly needle 
- 2 alcohol swabs 
 
Marketing Authorisation Holder and Manufacturer 
Octapharma AB, Lars Forssells gata 23, 112 75 Stockholm, Sweden 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Biotest AG (Germany) 
Tél/Tel: +49 6103 801-0 
 

Lietuva 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

България 
Biotest AG (Germany) 
Teл.: +49 6103 801-0 
 

Luxembourg/Luxemburg 
Biotest AG (Germany) 
Tél/Tel: +49 6103 801-0 
 

Česká republika 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Magyarország 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Danmark 
Biotest AG (Germany) 
Tlf: +49 6103 801-0 
 

Malta 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Deutschland 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Nederland 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Eesti 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Norge 
Biotest AG (Germany) 
Tlf: +49 6103 801-0 
 

Ελλάδα 
Biotest AG (Germany) 
Τηλ: +49 6103 801-0 
 

Österreich 
Biotest Austria GmbH 
Tel: +43 1 545 15 61-0 
 

España 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Polska 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

France 
Biotest AG (Germany) 
Tél: +49 6103 801-0 
 

Portugal 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Hrvatska 
Octapharma Nordic AB (Sweden) 
Tel: +46 8 56643000 

România 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Ireland Slovenija 



48 

Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Ísland 
Biotest AG (Germany) 
Sími: +49 6103 801-0 
 

Slovenská republika 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Italia 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Suomi/Finland 
Biotest AG (Germany) 
Puh/Tel: +49 6103 801-0 
 

Κύπρος 
Biotest AG (Germany) 
Τηλ: +49 6103 801-0 
 

Sverige 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

Latvija 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

United Kingdom 
Biotest AG (Germany) 
Tel: +49 6103 801-0 
 

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

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


49 

--------------------------------------------------------------------------------------------------------------------------- 
 
The following information is intended for healthcare professionals only: 
 
On-demand treatment 
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, Factor VIII activity should not fall below the given 
plasma activity level (in % of normal or IU/dl) in 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 (%) (IU/dL) 

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

Haemorrhage   

Early haemarthrosis, muscle 
bleeding or oral bleeding  

20–40 Repeat every 12 to 24 hours. 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 to 24 hours 
for 3 to 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 Every 24 hours, 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 therapy 
for at least another 7 days to maintain a 
Factor VIII activity of 30% to 
60% (IU/dL).  

 
  



50 

INSTRUCTIONS FOR PREPARATION AND ADMINISTRATION 
 

1. Allow the solvent syringe (water for injections) and the powder in the closed vial to reach 
room temperature. You can do this by holding them in your hands until they feel as warm as 
your hands. Do not use any other way to heat the vial and pre-filled syringe. This temperature 
should be maintained during reconstitution. 

2. Remove the plastic flip-top cap from the powder vial to expose the central portions of the 
rubber stopper. Do not remove the gray stopper or metal ring around the top of the vial.  

 
3. Wipe the top of the vial with an alcohol swab. Allow the alcohol to dry.  
4. Peel back the paper cover from the vial adapter package. Do not remove the adapter from the 

package.  

  
5. Place the powder vial on an even surface and hold it. Take the adapter package and place the 

vial adapter over the centre of the rubber stopper of the powder vial. Press down firmly the 
adapter package until the adapter spike penetrates the rubber stopper. The adapter snaps to the 
vial when done. 



51 

 
6. Peel back the paper cover from the pre-filled syringe package. Hold the plunger rod at the end 

and do not touch the shaft. Attach the threaded end of the plunger rod to the solvent syringe 
plunger. Turn the plunger rod clockwise until a slight resistance is felt. 

 
7. Break off the tamper-proof plastic tip from the solvent syringe by snapping the perforation of 

the cap. Do not touch the inside of the cap or the syringe tip. In case the solution is not used 
immediately close the filled syringe with the tamper-proof plastic tip for storage. 

 
8. Remove the adapter packaging and discard. 
9. Firmly connect the solvent syringe to the vial adapter by turning clockwise until resistance is 

felt. 



52 

 
10. Slowly inject all solvent into the powder vial by pressing down the plunger rod. 

 
11. Without removing the syringe, gently move or swirl the vial in circles a few times to dissolve 

the powder. Do not shake. Wait until all the powder dissolves completely. 
12. Visually inspect the final solution for particles before administration. The solution should be 

clear and colourless, practically free from visible particles. Do not use solutions that are 
cloudy or have deposits. 

13. Turn the vial attached to the syringe upside down, and slowly draw the final solution into the 
syringe. Make sure that the entire content of the vial is transferred to the syringe.  

 
14. Detach the filled syringe from the vial adapter by turning counter clockwise and discard the 

empty vial. 



53 

15. The solution is now prepared for immediate use. Do not refrigerate. 
16. Clean the chosen injection site with one of the provided alcohol swabs. 
17. Attach the provided infusion set to the syringe. 

Insert the needle of the infusion set into the chosen vein. If you have used a tourniquet to make 
the vein easier to see, this tourniquet should be released before you start injecting the solution. 
No blood must flow into the syringe due to the risk of formation of fibrin clots. 

18. Inject the solution into the vein at a slow speed, not faster than 4 ml per minute. 
 
If you use more than one vial of powder for one treatment, you may use the same injection needle 
again. The vial adapter and the syringe are for single use only. 
 
 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE 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
	A. LABELLING
	B. PACKAGE LEAFLET