NovoEight

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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1. NAME OF THE MEDICINAL PRODUCT 
 
NovoEight 250 IU powder and solvent for solution for injection 
NovoEight 500 IU powder and solvent for solution for injection 
NovoEight 1000 IU powder and solvent for solution for injection 
NovoEight 1500 IU powder and solvent for solution for injection 
NovoEight 2000 IU powder and solvent for solution for injection 
NovoEight 3000 IU powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
NovoEight 250 IU powder and solvent for solution for injection. 
Each powder vial contains nominally 250 IU human coagulation factor VIII (rDNA), turoctocog alfa.  
 
After reconstitution NovoEight contains approximately 62.5 IU/ml of human coagulation factor VIII 
(rDNA), turoctocog alfa.  
 
NovoEight 500 IU powder and solvent for solution for injection. 
Each powder vial contains nominally 500 IU human coagulation factor VIII (rDNA), turoctocog alfa.  
 
After reconstitution NovoEight contains approximately 125 IU/ml of human coagulation factor VIII 
(rDNA), turoctocog alfa. 
 
NovoEight 1000 IU powder and solvent for solution for injection. 
Each powder vial contains nominally 1000 IU human coagulation factor VIII (rDNA), turoctocog alfa. 
 
After reconstitution NovoEight contains approximately 250 IU/ml of human coagulation factor VIII 
(rDNA), turoctocog alfa. 
 
NovoEight 1500 IU powder and solvent for solution for injection. 
Each powder vial contains nominally 1500 IU human coagulation factor VIII (rDNA), turoctocog alfa.  
 
After reconstitution NovoEight contains approximately 375 IU/ml of human coagulation factor VIII 
(rDNA), turoctocog alfa.  
 
NovoEight 2000 IU powder and solvent for solution for injection. 
Each powder vial contains nominally 2000 IU human coagulation factor VIII (rDNA), turoctocog alfa.  
 
After reconstitution NovoEight contains approximately 500 IU/ml of human coagulation factor VIII 
(rDNA), turoctocog alfa.  
 
NovoEight 3000 IU powder and solvent for solution for injection. 
Each powder vial contains nominally 3000 IU human coagulation factor VIII (rDNA), turoctocog alfa.  
 
After reconstitution NovoEight contains approximately 750 IU/ml of human coagulation factor VIII 
(rDNA), turoctocog alfa.  
 
The potency (IU) is determined using the European Pharmacopoeia (Ph. Eur) chromogenic assay. The 
specific activity of NovoEight is approximately 8,300 IU/mg protein. 
 
Turoctocog alfa (human coagulation factor VIII (rDNA)) is a purified protein that has 1,445 amino 
acids with an approximate molecular mass of 166 kDA. It is produced by recombinant DNA 
technology in Chinese hamster ovary (CHO) cells, and prepared without the addition of any human or 
animal derived protein in the cell culture process, purification or final formulation. 
 



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Turoctocog alfa is a B-domain truncated recombinant human coagulation factor VIII (B-domain 
consists of 21 amino acids of the wild type B-domain) without any other modifications in the amino 
acid sequence. 
 
Excipient with known effect  
The medicinal product contains 30.5 mg sodium per reconstituted vial. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection. 
 
White or slightly yellow powder or friable mass.  
 
Clear and colourless solution for injection. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII 
deficiency). 
 
NovoEight can be used for all age groups. 
 
4.2 Posology and method of administration 
 
Treatment should be under the supervision of a doctor 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 injections. 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 a single dose pharmacokinetic study 
in adult patients the maximum exposure (Cmax) and the total exposure (AUC) increased with increasing 
body mass index (BMI) indicating that dose adjustments may be required. An increase in dose may be 
required for underweight patients (BMI <18.5 kg/m2) and a decrease in dose may be required for obese 
patients (BMI ≥30 kg/m2), but there is insufficient data to recommend specific dose adjustments, see 
section 5.2. 
 
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 the patient’s clinical condition. 
 



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The number of units of factor VIII administered is expressed in International Units (IU), which are 
related to the current WHO standard for factor VIII products. The activity of factor VIII in plasma is 
expressed either as percentage (relative to normal level human plasma) or in International Units 
(relative to an International Standard for factor VIII in plasma).  
 
One International Unit (IU) of factor VIII activity is equivalent to that quantity of factor VIII in one ml 
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 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). 
 
The amount to be administered and the frequency of administration should always be oriented to the 
clinical effectiveness in the individual case. 
 
In the case of the following haemorrhagic events, the factor VIII activity should not fall below the 
given plasma activity level (in % of normal or IU/dl) in the corresponding period. The following table 
can be used to guide dosing in bleeding episodes and surgery: 
 
Table 1 Guide for dosing in bleeding episodes and surgery 
Degree of haemorrhage/Type of 
surgical procedure 

FVIII 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 achieved 

 
 
More extensive haemarthrosis, 
muscle bleeding or haematoma 

 
 
30–60 

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

 
Life threatening haemorrhages 

 
60–100 

 
Repeat infusion every 8 to 24 hours 
until threat is resolved 
 

Surgery   
Minor surgery including tooth 
extraction 
 

30–60 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 
recommended doses are 20–40 IU of factor VIII per kg body weight every second day or 20–50 IU of 
factor VIII per kg body weight 3 times weekly. In adults and adolesents (>12 years) a less frequent 



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regimen (40-60 IU/kg every third day or twice weekly) may be applicable. In some cases, especially in 
younger patients, shorter dosage intervals or higher doses may be necessary.  
 
Surgery 
There is limited experience of surgery in paediatric patients. 
 
Elderly  
There is no experience in patients >65 years.  
 
Paediatric population 
For long term prophylaxis against bleeding in patients below the age of 12, doses of 25–50 IU of 
factor VIII per kg body weight every second day or 25–60 IU of factor VIII per kg body weight 
3 times weekly are recommended. For paediatric patients above the age of 12 the dose 
recommendations are the same as for adults. 
 
Method of administration 
Intravenous use.  
 
The recommended infusion rate for NovoEight is 1–2 ml/min. The rate should be determined by the 
patient’s comfort level. 
 
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. 
 
Known allergic reaction to hamster proteins. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve traceability of biological medicinal products, the name and the batch number of 
the administered product should be clearly recorded. 
 
Hypersensitivity 
Allergic type hypersensitivity reactions are possible with NovoEight. The product contains traces of 
hamster proteins, which in some patients may cause allergic reactions. 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 50 exposure 
days but continues throughout life although the risk is uncommon. 
 
The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titre 
posing less of a risk of insufficient clinical response than high titre inhibitors.  
In general, all patients treated with coagulation factor VIII products should be carefully monitored for 
the development of inhibitors by appropriate clinical observation and laboratory test. If the expected 
factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate 



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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 event 
In patients with existing cardiovascular risk factors, substitiution therapy with FVIII may increase the 
cardiovascular risk. 
 
Catheter-related complications 
If a central venous access device (CVAD) is required, risk of CVAD-related complications including 
local infections, bacteraemia and catheter site thrombosis should be considered. 
 
It is strongly recommended that every time that NovoEight 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 
The medicinal product contains 30.5 mg sodium per reconstituted vial, equivalent to 1.5% of the 
WHO recommended maximum daily intake of 2 g sodium for an adult.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interactions of human coagulation factor VIII (rDNA) products with other medicinal products have 
been reported. 
 
4.6 Fertility, pregnancy and lactation 
 
Animal reproduction studies have not been conducted with NovoEight. Based on the rare occurrence 
of haemophilia A in women, experience regarding the use of factor VIII during pregnancy and 
breastfeeding is not available. Therefore, factor VIII should be used during pregnancy and lactation 
only if clearly indicated.  
 
4.7 Effects on ability to drive and use machines 
 
NovoEight 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 angioedema, burning and stinging at the 
infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, 
restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed 
rarely and may in some cases progress to severe anaphylaxis (including shock). 
 
Very rarely development of antibodies to hamster protein with related hypersensitivity reactions has 
been observed. 
 
Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated 
with factor VIII, including with NovoEight. 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 is contacted. 
 
Tabulated list of adverse reactions 



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The table 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), and not known (cannot be estimated from the available data). 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
Table 2 Frequency of adverse drug reactions in clinical trials  
System Organ Class Frequencya in 

PTPs 
Frequencya in 
PUPs 

Adverse reaction 

Blood and lymphatic 
system disorders 

Uncommonb Very commonb FVIII inhibition  

Psychiatric disorders Uncommon  Insomnia 
Nervous system 
disorders 

Uncommon  Headache, dizziness, burning 
sensation 

Cardiac disorders Uncommon  Sinus tachycardia, acute 
myocardial infarction 

Vascular disorders Uncommon  Hypertension, lymphoedema, 
hyperaemia 

 Common Flushing, Thrombophlebitis 
superficial 

Skin and subcutaneous 
tissue disorders  

 Common Rash, rash erythematous 
Uncommon  Rash, lichenoid keratosis, skin 

burning sensation 
Musculoskeletal and 
connective tissue 
disorders 

Uncommon   Musculoskeletal stiffness, 
arthropathy, pain in extremity, 
musculoskeletal pain 

 Common Haemarthrosis, Muscle 
haemorrhage 

Respiratory, thoracic 
and mediastinal 
disorders 

 Common Cough  

General disorders and 
administration site 
conditions 

Common   Injection site reactionsc 
 Common Pyrexia, catheter site erythema 
Uncommon   Fatigue, feeling hot, oedema 

peripheral, pyrexia 
Investigations Common  Hepatic enzymes increasedd 

 Common Anti factor VIII antibody 
positive 

Uncommon   Heart rate increased  
Gastrointestinal 
disorders 

 Common Vomiting 

Injury, poisoning and 
procedural 
complications 

Common  Incorrect dose administered 
 Common Infusion related reaction 
Uncommon   Contusion 

Product issues  Common Thrombosis in device 
a Calculated based on total number of unique patients in all clinical trials (301), of which 242 

were previously treated patients (PTPs) and 60 were previously untreated patients (PUPs).  
b Frequency is based on studies with all FVIII products which included patients with severe 

haemophilia A.  
c Injection site reactions include injection site erythema, injection site extravasation and injection 

site pruritus. 
d Hepatic enzymes increased include alanine aminotransferase, aspartate aminotransferase, 

gamma-glutamyltransferase and bilirubin. 
 



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Description of selected adverse reactions 
During all clinical studies with NovoEight in previously treated patients, a total of 35 adverse 
reactions were reported in 23 of 242 patients exposed to NovoEight. The most frequently reported 
adverse reactions were injection site reactions, incorrect dose administered and hepatic enzymes 
increased. Of the 35 adverse reactions, 2 were reported in 1 out of 31 patients below 6 years of age, 
none in patients from 6 to ≤12 years of age, 1 event in 1 out of 24 patients (12 to <18 years of age) and 
32 were reported in 21 out of 155 adults (≥18 years). 
 
Paediatric population 
In clinical trials involving 63 previously treated paediatric patients between 0 and 12 years of age and 
24 adolescents between 12 and 18 years of age with severe haemophilia A no difference in the safety 
profile of NovoEight was observed between paediatric patients and adults. 
 
In the trial with previously untreated patients, between 0 and 6 years of age, a total of 46 adverse 
reactions were reported in 33 of 60 patients exposed to NovoEight. The most frequently reported 
adverse reaction was Factor VIII inhibition, see section 4.4. High risk genetic mutations were 
identified in 92.3% of the overall and 93.8% of the high titre confirmed inhibitors. No other factors 
were significantly associated with inhibitor development.  
 
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 recombinant coagulation factor VIII have been reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor VIII, ATC code: B02BD02. 
 
Mechanism of action 
NovoEight contains turoctocog alfa, a human coagulation factor VIII (rDNA), with a truncated B-
domain. This glycoprotein has the same structure as human factor VIII when activated, and post-
translational modifications that are similar to those of the plasma-derived molecule. The tyrosine 
sulphation site present at Tyr1680 (native full length), which is important for the binding to von 
Willebrand factor, has been found to be fully sulphated in the turoctocog alfa molecule. When infused 
into a haemophilia patient, factor VIII binds to endogenous von Willebrand Factor in the patient’s 
circulation. The factor VIII/von Willebrand factor complex consists of two molecules (factor VIII and 
von Willebrand factor) with different physiological functions. Activated factor VIII acts as a co-factor 
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 a result of accidental or surgical trauma. By replacement therapy the plasma levels 
of factor VIII are increased, thereby enabling a temporary correction of the factor deficiency and 
correction of bleeding tendencies.  
 
Of note, annualised bleeding rate (ABR) is not comparable between different factor concentrates and 
between different clinical studies. 
 
Clinical efficacy 

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


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Four multi-centre, open-labelled, non-controlled trials have been conducted to evaluate the safety and 
efficacy of NovoEight in the prevention and treatment of bleeds and during surgery in patients with 
severe haemophilia A (FVIII activity ≤1%). Three of these trials were performed in previously treated 
patients and the fourth in previously untreated patients. The trials included 298 exposed patients; 175 
adolescents or adult patients without inhibitors from the age of 12 years (≥150 exposure days), 63 
previously treated paediatric patients without inhibitors below 12 years of age (≥50 exposure days) 
and 60 previously untreated patients below 6 years of age.  
188 out of 238 previously treated patients continued into the safety extension trial. Treatment with 
NovoEight was shown to be safe and had the intended haemostatic and preventive effect.  
Of the 3,293 reported bleeds observed in 298 of the patients, 2,902 (88.1%) of the bleeds were 
resolved with 1-2 infusions of NovoEight. 
 
Table 3 Consumption of NovoEight and haemostatic success rates in previously untreated 
patients (PUP) and previously treated patients (PTP) 
 Younger 

children 
(0 – 
<6 years) 
PUP 

Younger 
children 
(0 – 
<6 years) 
PTP 

Older 
children 
(6 – 
<12 years) 
PTP 

Adolescents 
(12 – 
<18 years) 
PTP 

Adults 
(≥18 years) 
PTP 

Total 

Number of 
patients 

60 31 32 24 151 298 

Dose used for 
prevention 
per patient 
(IU/kg BW)  
Mean (SD) 
Min ; Max 

 
 
 
 
45.2 (14.4) 
4.5 ; 363.8 

 
 
 
 
41.5 (8.1) 
3.4 ; 196.3. 

 
 
 
 
38.4 (9.4) 
3.2 ; 62.5 

 
 
 
 
28.5 (9.3) 
17.4 ; 73.9 

 
 
 
 
28.5 (8.3) 
12.0 ; 97.4 

 
 
 
 
32.8 (10.9) 
3.2 ; 363.8 

Dose used for 
treatment of 
bleed (IU/kg 
BW) 
Mean (SD) 
Min ; Max 

 
 
 
43.6 (15.2) 
11.9 ; 118.9 

 
 
 
44.0 (12.6) 
21.4 ; 193.8 

 
 
 
40.4 (10.5) 
24.0 ; 71.4 

 
 
 
29.3 (10.3) 
12.4 ; 76.8 

 
 
 
35.0 (12.3) 
6.4 ; 104.0 

 
 
 
37.5 (13.4) 
6.4 ; 193.8 

Success ratea 
% 

87.0% 92.2% 
 

88.4% 
 

85.1% 
 

89.6% 
 

88.9% 
 

BW: Body weight, SD: Standard deviation 
a Success is defined as either 'Excellent' or 'Good'. 
 
A total of 30 surgeries were performed in 25 patients of which 26 were major surgeries and 4 were 
minor. Haemostasis was successful in all surgeries and no treatment failures were reported. 
 
Data on Immune Tolerance Induction (ITI) has been collected in patients with haemophilia A who had 
developed inhibitors to factor VIII. During clinical trial in PUPs, 21 patients were treated with ITI and 
18 (86%) patients completed ITI with a negative inhibitor test result.  
 
5.2 Pharmacokinetic properties 
 
All pharmacokinetic (PK) studies with NovoEight were conducted after i.v. administration of 50 IU/kg 
NovoEight in previously treated patients with severe haemophilia A (FVIII ≤1%). The analysis of 
plasma samples was conducted using both the one-stage clotting assay and the chromogenic assay.  
The assay performance of NovoEight in FVIII:C assays was evaluated and compared to a marketed 
full length recombinant FVIII product. The study showed that comparable and consistent results were 
obtained for both products and that NovoEight can be reliably measured in plasma without the need of 
a separate NovoEight standard. 
 
The single dose pharmacokinetic parameters of NovoEight are listed in Table 4 for the one-stage 
clotting assay and in Table 5 for the chromogenic assay.  



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Table 4 Single-dose pharmacokinetic parameters of NovoEight (50 IU/kg) by age - one stage 
clotting assay - Mean (SD) 
Parameter  0 − <6 years 6 − <12 years ≥12 years  

n=14 n=14 n=33 
Incremental recovery 
(IU/dl)/(IU/kg) 

1.8 (0.7)  2.0 (0.4) 2.2 (0.4) 

AUC ((IU*h)/dl) 992 (411)  1109(374) 1526 (577) 
CL (ml/h/kg) 6.21 (3.66) 5.02 (1.68) 3.63 (1.09) 
t½ (h) 7.65 (1.84)  8.02 (1.89) 11.00 (4.65) 
Vss (ml/kg) 56.68 (26.43)  46.82 (10.63) 47.40 (9.21) 
Cmax (IU/dl) 100 (58)  107 (35) 123 (41) 
Mean residence time 
(h) 

9.63 (2.50)  9.91 (2.57) 14.19 (5.08) 

Abbreviations: AUC = area under the factor VIII activity time profile; CL = clearance; t1/2 = terminal 
half-life; Vss = volume of distribution at steady-state; Cmax = maximum factor VIII activity. 
 
Table 5 Single-dose pharmacokinetic parameters of NovoEight (50 IU/kg) by age - chromogenic 
assay - Mean (SD) 
Parameter 0 − <6 years 6 − <12 years ≥12 years  

n=14 n=14 n=33 
Incremental recovery 
(IU/dl)/(IU/kg) 

2.2 (0.6) 2.5 (0.6) 2.9 (0.6) 

AUC ((IU*h)/dl) 1223 (436) 1437 (348) 1963 (773) 
CL (ml/h/kg) 4.59 (1.73) 3.70 (1.00) 2.86 (0.94) 
t½ (h) 9.99 (1.71) 9.42 (1.52) 11.22 (6.86) 
Vss (ml/kg) 55.46 (23.53) 41.23 (6.00) 38.18 (10.24) 
Cmax (IU/dl) 112 (31) 125 (27) 163 (50) 
Mean residence time 
(h) 

12.06 (1.90) 11.61 (2.32) 14.54 (5.77) 

Abbreviations: AUC = area under the factor VIII activity time profile; CL = clearance; t1/2 = terminal 
half-life; Vss = volume of distribution at steady-state; Cmax = maximum factor VIII activity. 
 
The pharmacokinetic parameters were comparable between paediatric patients below 6 years of age 
and the paediatric patients from 6 to below 12 years of age. Some variation was observed in the 
pharmacokinetic parameters of NovoEight between paediatric and adult patients. The higher CL and 
the shorter t½ seen in paediatric patients compared to adult patients with haemophilia A may be due in 
part to the known higher plasma volume per kilogram body weight in younger patients. 
 
A single dose pharmacokinetic trial (50 IU/kg) was performed in 35 haemophilia patients (≥18 years 
of age) in different BMI categories. The maximum exposure (Cmax) and the total exposure (AUC) 
increase with increasing BMI indicating that dose adjustments may be required for underweight (BMI 
<18.5 kg/m2) and obese patients (BMI ≥30 kg/m2), see section 4.2.  
 
Table 6 Single-dose pharmacokinetic parameters of NovoEight (50 IU/kg) by BMI classesa – 
One-stage clotting assay - Mean (SD) 
PK parameter Underweight 

N=5 
Normal weight 
N=7 

Overweight 
N=8 

Obese class I 
N=7 

Obese class II/III 
N=7 

Incremental 
recovery 
(IU/dl)/(IU/kg) 

1.7 (0.2) 2.0 (0.2) 2.4 (0.4) 2.3 (0.3)b 2.6 (0.3) 

AUC ((IU*h)/dl) 1510 (360) 1920 (610) 1730 (610) 2030 (840) 2350 (590) 
CL (ml/h/kg) 3.91 (0.94) 3.20 (1.00) 3.63 (1.24) 3.37 (1.79) 2.51 (0.63) 
t½ (h) 11.3 (2.0) 11.7 (3.5) 9.4 (2.9) 11.2 (3.5) 11.1 (2.7) 



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Vss (ml/kg) 56.8 (5.4) 44.8 (6.5) 39.6 (6.0) 42.0 (9.0) 35.0 (4.6) 
Cmax (IU/dl) 100 (11) 121 (10) 144 (26) 140 (21) 161 (32) 
Mean residence 
time (h) 

15.1 (3.0) 15.3 (4.8) 11.9 (3.7) 14.4 (4.6) 14.6 (3.7) 

a BMI groups: Underweight: BMI <18.5 kg/m2, Normal weight: BMI 18.5-24.9 kg/m2, Overweight: 
BMI 25-29.9 kg/m2, Obese class I: BMI 30-34.9 kg/m2, Obese class II/III: BMI ≥35 kg/m2. 
b Based on 6 patients only. 
 
Table 7 Single-dose pharmacokinetic parameters of NovoEight (50 IU/kg) by BMI classesa – 
Chromogenic assay - Mean (SD) 
PK parameter Underweight 

N=5 
Normal weight 
N=7 

Overweight 
N=9 

Obese class I 
N=7 

Obese class 
II/III N=7 

Incremental 
recovery 
(IU/dl)/(IU/kg) 

2.2 (0.4) 2.9 (0.3) 3.0 (0.5) 3.2 (0.5) 3.5 (0.5) 

AUC ((IU*h)/dl) 1860 (700) 2730 (860) 2310 (1020) 2780 (1210) 3050 (730) 
CL (ml/h/kg) 3.28 (0.87) 2.25 (0.73) 2.84 (1.09) 2.58 (1.56) 1.94 (0.52) 
t½ (h) 11.7 (2.4) 11.5 (3.6) 9.7 (3.4) 10.4 (3.2) 10.5 (2.5) 
Vss (ml/kg) 49.1 (10.4) 31.2 (4.5) 31.6 (5.8) 28.9 (5.1) 25.7 (4.0) 
Cmax (IU/dl) 138 (29) 185 (24) 194 (31) 200 (33) 227 (32) 
Mean residence 
time (h) 

15.5 (3.2) 15.2 (4.9) 12.6 (4.8) 13.5 (4.6) 13.9 (3.7) 

a BMI groups: Underweight: BMI <18.5 kg/m2, Normal weight: BMI 18.5-24.9 kg/m2, Overweight: 
BMI 25-29.9 kg/m2, Obese class I: BMI 30-34.9 kg/m2, Obese class II/III: BMI ≥35 kg/m2. 
 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special concern for humans based on conventional studies of safety 
pharmacology and repeated dose toxicity. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder: 
Sodium chloride 
L-histidine 
Sucrose 
Polysorbate 80 
L-methionine 
Calcium chloride dihydrate 
Sodium hydroxide (for pH adjustment) 
Hydrochloric acid (for pH adjustment) 
 
Solvent: 
Sodium chloride 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 



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Unopened vial 
30 months when stored in a refrigerator (2°C – 8°C).  
 
During the shelf life, the product may be kept at: 
• room temperature (≤ 30°C) for a single period no longer than 9 months 
 or 
• above room temperature (30°C up to 40°C) for a single period no longer than 3 months. 
 
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 and the storage temperature on the product carton.  
 
After reconstitution: 
Chemical and physical in-use stability have been demonstrated for: 
• 24 hours stored at 2°C – 8°C 
• 4 hours stored at 30°C, for product which has been kept for a single period no longer than 

9 months at room temperature (≤30°C) 
• 4 hours stored up to 40°C, for product which has been kept for a single period no longer than 

3 months at above room temperature (30°C up to 40°C). 
 
From a microbiological point of view, the medicinal 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 and would normally not be longer than as stated above, unless reconstitution 
has taken place in controlled and validated aseptic conditions. 
 
Any unused reconstituted product stored at room temperature (≤30°C) or up to 40°C for more than 
4 hours should be discarded. 
 
6.4 Special precautions for storage 
 
Store in 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 (≤30°C) or up to 40°C and storage conditions after reconstitution of 
the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container  
 
Each pack of NovoEight 250 IU, 500 IU, 1000 IU, 1500 IU, 2000 IU and 3000 IU powder and solvent 
for solution for injection contains: 
 
– 1 glass vial (type I) with powder and chlorobutyl rubber stopper  
– 1 sterile vial adapter for reconstitution 
– 1 pre-filled syringe of 4 ml solvent with backstop (polypropylene), a rubber plunger 

(bromobutyl) and a syringe cap with a stopper (bromobutyl)  
– 1 plunger rod (polypropylene). 
 
6.6 Special precautions for disposal and other handling 
 
NovoEight is to be administered intravenously after reconstitution of the powder with the solvent 
supplied in the syringe. After reconstitution the solution appears as a clear or slightly opalescent 
solution. Do not use solutions that are cloudy or have deposits. 
 



13 

You will also need an infusion set (tubing and butterfly needle), sterile alcohol swabs, gauze pads and 
plasters. These devices are not included in the NovoEight package.  
 
Always use an aseptic technique.  
 
Reconstitution 
 
A) 
Take the vial, the vial adapter and the pre-filled 
syringe out of the carton. Leave the plunger rod 
untouched in the carton. Bring the vial and the 
pre-filled syringe to 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. 
 

 
 

 

 A 

 
 

B) 
Remove the plastic cap from the vial. If the 
plastic cap is loose or missing, do not use the 
vial. Wipe the rubber stopper on the vial with a 
sterile alcohol swab and allow it to air dry for a 
few seconds before use. 

 

 

 B 

 
 

C) 
Remove the protective paper from the vial 
adapter. If the protective paper is not fully 
sealed or if it is broken, do not use the vial 
adapter. 
Do not take the vial adapter out of the protective 
cap with your fingers.  

 

 

 C 

 
 

D) 
Turn over the protective cap and snap the vial 
adapter onto the vial. Once attached do not 
remove the vial adapter from the vial. 

 

 

 D 

 
 



14 

E) 
Lightly squeeze the protective cap with your 
thumb and index finger as shown. Remove the 
protective cap from the vial adapter. 

 
 E 

 
 

F) 
Grasp the plunger rod by the wide top and 
immediately connect the plunger rod to the 
syringe by turning it clockwise into the plunger 
inside the pre-filled syringe until resistance is 
felt. 
 

 

 

 F 

 
 

G) 
Remove the syringe cap from the pre-filled 
syringe by bending it down until the perforation 
breaks. Do not touch the syringe tip under the 
syringe cap. 

 

 

 G 

 
 

H) 
Screw the pre-filled syringe securely onto the 
vial adapter until resistance is felt. 

 

 

 H 

 
 

I) 
Hold the pre-filled syringe slightly tilted with 
the vial pointing downwards. Push the plunger 
rod to inject all the solvent into the vial. 

 

 

 I 

 
 



15 

J) 
Keep the plunger rod pressed down and swirl 
the vial gently until all the powder is dissolved. 
Do not shake the vial as this will cause foaming.  

 

 

 J 

 
 

 
It is recommended to use NovoEight immediately after reconstitution. For storage conditions of the 
reconstituted medicinal product see section 6.3. 
 
If a larger dose is needed, repeat steps A to J with additional vials, vial adapters and pre-filled 
syringes. 
 
Administration of the reconstituted solution 
 
K) 
Keep the plunger rod pushed completely in. 
Turn the syringe with the vial upside down. Stop 
pushing the plunger rod and let it move back on 
its own while the reconstituted solution fills the 
syringe. Pull the plunger rod slightly downwards 
to draw the reconstituted solution into the 
syringe. 
 
In case you only need part of the entire vial, use 
the scale on the syringe to see how much 
reconstituted solution you withdraw, as 
instructed by your doctor or nurse. 
 
While holding the vial upside down, tap the 
syringe gently to let any air bubbles rise to the 
top. Push the plunger rod slowly until all air 
bubbles are gone. 
 

 
 

 

 K 

 
 

L) 
Unscrew the vial adapter with the vial.  
 
 
 
 
 
 
 
NovoEight is now ready for injection. Locate a 
suitable site and slowly inject NovoEight into 
the vein over a period of 2-5 minutes. 

 

 

 L 

 
 

 



16 

Disposal 
After injection, safely dispose of all unused NovoEight solution, the syringe with the infusion set, the 
vial with the vial adapter and other waste materials as instructed by your pharmacist.  
 
Do not throw it out with the ordinary household waste.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
8. MARKETING AUTHORISATION NUMBERS  
 
NovoEight 250 IU 
EU/1/13/888/001 
 
NovoEight 500 IU 
EU/1/13/888/002 
 
NovoEight 1000 IU 
EU/1/13/888/003 
 
NovoEight 1500 IU 
EU/1/13/888/004 
 
NovoEight 2000 IU 
EU/1/13/888/005 
 
NovoEight 3000 IU 
EU/1/13/888/006 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 13 November 2013 
Date of latest renewal: 30 July 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 

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


17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

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

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 

SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 
 



18 

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

 
Name and address of the manufacturers of the biological active substance  
 
BioReliance Ltd 
Todd Campus, West of Scotland Science Park, 
Glasgow, G20 0XA 
United Kingdom 
 
Novo Nordisk US Bio Production Inc. 
9 Technology Drive 
West Lebanon 
NH 03784 
USA 
 
Name and address of the manufacturer responsible for batch release 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
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 (PSUR) 
 
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.  



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 



21 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
NovoEight 250 IU powder and solvent for solution for injection 
 
turoctocog alfa (human coagulation factor VIII (rDNA)) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One ml of NovoEight contains approximately 62.5 IU of human coagulation factor VIII (rDNA), 
turoctocog alfa after reconstitution  
 
 
3. LIST OF EXCIPIENTS 
 
Powder: Sodium chloride, L-histidine, sucrose, polysorbate 80, L-methionine, calcium chloride 
dihydrate, sodium hydroxide, hydrochloric acid 
Solvent: Sodium chloride, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection  
 
Pack contains: 1 powder vial, 4 ml solvent in pre-filled syringe, plunger rod and vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Intravenous use  
 
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 WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



22 

Store in a refrigerator. Do not freeze 
 
During storage, the product may be kept at: 
• room temperature (≤ 30°C) for a single period no longer than 9 months or  
• above room temperature (30°C up to 40°C) for a single period no longer than 3 months 
 
Taken out of refrigerator: _____________Stored at ≤30°C __ Stored at 30°C up to 40°C __ 
 
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 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBERS  
 
EU/1/13/888/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
NovoEight 250 IU 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 



23 

NN:



24 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
NovoEight 250 IU powder for solution for injection 
 
turoctocog alfa 
 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
250 IU  
 
 
6. OTHER 
 
Novo Nordisk A/S 



25 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
NovoEight 500 IU powder and solvent for solution for injection 
 
turoctocog alfa (human coagulation factor VIII (rDNA)) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One ml of NovoEight contains approximately 125 IU of human coagulation factor VIII (rDNA), 
turoctocog alfa after reconstitution  
 
 
3. LIST OF EXCIPIENTS 
 
Powder: Sodium chloride, L-histidine, sucrose, polysorbate 80, L-methionine, calcium chloride 
dihydrate, sodium hydroxide, hydrochloric acid 
Solvent: Sodium chloride, water for injections  
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection  
 
Pack contains: 1 powder vial, 4 ml solvent in pre-filled syringe, plunger rod and vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Intravenous use  
 
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 WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



26 

Store in a refrigerator. Do not freeze 
 
During storage, the product may be kept at: 
• room temperature (≤ 30°C) for a single period no longer than 9 months or  
• above room temperature (30°C up to 40°C) for a single period no longer than 3 months 
 
Taken out of refrigerator: _____________Stored at ≤30°C __ Stored at 30°C up to 40°C __ 
 
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 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBERS  
 
EU/1/13/888/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
NovoEight 500 IU 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 



27 

NN: 



28 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
NovoEight 500 IU powder for solution for injection 
 
turoctocog alfa 
 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
500 IU  
 
 
6. OTHER 
 
Novo Nordisk A/S 



29 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
NovoEight 1000 IU powder and solvent for solution for injection 
 
turoctocog alfa (human coagulation factor VIII (rDNA)) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One ml of NovoEight contains approximately 250 IU of human coagulation factor VIII (rDNA), 
turoctocog alfa after reconstitution  
 
 
3. LIST OF EXCIPIENTS 
 
Powder: Sodium chloride, L-histidine, sucrose, polysorbate 80, L-methionine, calcium chloride 
dihydrate, sodium hydroxide, hydrochloric acid 
Solvent: Sodium chloride, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection  
 
Pack contains: 1 powder vial, 4 ml solvent in pre-filled syringe, plunger rod and vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Intravenous use  
 
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 WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



30 

Store in a refrigerator. Do not freeze 
 
During storage, the product may be kept at: 
• room temperature (≤ 30°C) for a single period no longer than 9 months or  
• above room temperature (30°C up to 40°C) for a single period no longer than 3 months 
 
Taken out of refrigerator: _____________Stored at ≤30°C __ Stored at 30°C up to 40°C __ 
 
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 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBERS  
 
EU/1/13/888/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
NovoEight 1000 IU 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 



31 

NN: 



32 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
NovoEight 1000 IU powder for solution for injection 
 
turoctocog alfa 
 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1000 IU  
 
 
6. OTHER 
 
Novo Nordisk A/S 



33 

 
 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
NovoEight 1500 IU powder and solvent for solution for injection 
 
turoctocog alfa (human coagulation factor VIII (rDNA)) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One ml of NovoEight contains approximately 375 IU of human coagulation factor VIII (rDNA), 
turoctocog alfa after reconstitution  
 
 
3. LIST OF EXCIPIENTS 
 
Powder: Sodium chloride, L-histidine, sucrose, polysorbate 80, L-methionine, calcium chloride 
dihydrate, sodium hydroxide, hydrochloric acid 
Solvent: Sodium chloride, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection  
 
Pack contains: 1 powder vial, 4 ml solvent in pre-filled syringe, plunger rod and vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Intravenous use  
 
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 WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



34 

 
Store in a refrigerator. Do not freeze 
 
During storage, the product may be kept at: 
• room temperature (≤ 30°C) for a single period no longer than 9 months or  
• above room temperature (30°C up to 40°C) for a single period no longer than 3 months 
 
Taken out of refrigerator: _____________Stored at ≤30°C __ Stored at 30°C up to 40°C __ 
 
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 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBERS  
 
EU/1/13/888/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
NovoEight 1500 IU 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 



35 

SN: 
NN: 



36 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
NovoEight 1500 IU powder for solution for injection 
 
turoctocog alfa 
 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1500 IU  
 
 
6. OTHER 
 
Novo Nordisk A/S 



37 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
NovoEight 2000 IU powder and solvent for solution for injection 
 
turoctocog alfa (human coagulation factor VIII (rDNA)) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One ml of NovoEight contains approximately 500 IU of human coagulation factor VIII (rDNA), 
turoctocog alfa after reconstitution  
 
 
3. LIST OF EXCIPIENTS 
 
Powder: Sodium chloride, L-histidine, sucrose, polysorbate 80, L-methionine, calcium chloride 
dihydrate, sodium hydroxide, hydrochloric acid 
Solvent: Sodium chloride, water for injections  
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection  
 
Pack contains: 1 powder vial, 4 ml solvent in pre-filled syringe, plunger rod and vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Intravenous use  
 
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 WARNINGS, IF NECESSARY 
 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 



38 

 
Store in a refrigerator. Do not freeze 
 
During storage, the product may be kept at: 
• room temperature (≤ 30°C) for a single period no longer than 9 months or  
• above room temperature (30°C up to 40°C) for a single period no longer than 3 months 
 
Taken out of refrigerator: _____________Stored at ≤30°C __ Stored at 30°C up to 40°C __ 
 
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 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBERS  
 
EU/1/13/888/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
NovoEight 2000 IU 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 



39 

SN: 
NN:



40 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
NovoEight 2000 IU powder for solution for injection  
 
turoctocog alfa 
 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2000 IU  
 
 
6. OTHER 
 
Novo Nordisk A/S 



41 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
Carton 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
NovoEight 3000 IU powder and solvent for solution for injection 
 
turoctocog alfa (human coagulation factor VIII (rDNA)) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
One ml of NovoEight contains approximately 750 IU of human coagulation factor VIII (rDNA), 
turoctocog alfa after reconstitution  
 
 
3. LIST OF EXCIPIENTS 
 
Powder: Sodium chloride, L-histidine, sucrose, polysorbate 80, L-methionine, calcium chloride 
dihydrate, sodium hydroxide, hydrochloric acid 
Solvent: Sodium chloride, water for injections  
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Powder and solvent for solution for injection  
 
Pack contains: 1 powder vial, 4 ml solvent in pre-filled syringe, plunger rod and vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Intravenous use  
 
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 WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 



42 

Store in a refrigerator. Do not freeze 
 
During storage, the product may be kept at: 
• room temperature (≤ 30°C) for a single period no longer than 9 months or  
• above room temperature (30°C up to 40°C) for a single period no longer than 3 months 
 
Taken out of refrigerator: _____________Stored at ≤30°C __ Stored at 30°C up to 40°C __ 
 
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 
 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
12. MARKETING AUTHORISATION NUMBERS  
 
EU/1/13/888/006 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
NovoEight 3000 IU 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 
 
PC: 
SN: 



43 

NN:



44 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Vial 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
NovoEight 3000 IU powder for solution for injection 
 
turoctocog alfa 
 
Intravenous use 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
3000 IU  
 
 
6. OTHER 
 
Novo Nordisk A/S 



45 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
Pre-filled syringe 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION 
 
Solvent for NovoEight 
 
Sodium chloride 9 mg/ml 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
4 ml 
 
 
6. OTHER 
 
Novo Nordisk A/S 



46 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



47 

Package leaflet: Information for the user 
 

NovoEight 250 IU powder and solvent for solution for injection 
NovoEight 500 IU powder and solvent for solution for injection 
NovoEight 1000 IU powder and solvent for solution for injection 
NovoEight 1500 IU powder and solvent for solution for injection 
NovoEight 2000 IU powder and solvent for solution for injection 
NovoEight 3000 IU powder and solvent for solution for injection 

 
turoctocog alfa (human coagulation factor VIII (rDNA)) 

 
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 NovoEight is and what it is used for  
2. What you need to know before you use NovoEight  
3. How to use NovoEight  
4. Possible side effects  
5. How to store NovoEight  
6. Contents of the pack and other information 
 
 
1. What NovoEight is and what it is used for 
 
NovoEight contains the active substance turoctocog alfa, human coagulation factor VIII. Factor VIII is 
a protein naturally found in the blood that helps it to clot. 
 
NovoEight is used to treat and prevent bleeding episodes in patients with haemophilia A (inborn factor 
VIII deficiency) and can be used for all age groups. 
 
In patients with haemophilia A, factor VIII is missing or not working properly. NovoEight replaces 
this faulty or missing ‘factor VIII’ and helps blood to form clots at the site of bleeding. 
 
 
2. What you need to know before you use NovoEight 
 
Do not use NovoEight: 
• if you are allergic to the active substance or to any of the other ingredients of this medicine 

(listed in section 6) 
• if you are allergic to hamster proteins. 
 
Do not use NovoEight if either of the above applies to you. If you are not sure, talk to your doctor 
before using this medicine. 
 
Warnings and precautions 
 
Talk to your doctor before using NovoEight. 
 
There is a rare chance that you may experience an anaphylactic reaction (a severe, sudden allergic 
reaction) to NovoEight. Early signs of allergic reactions are rash, hives, weals, generalised itching, 



48 

swelling of lips and tongue, difficulty in breathing, wheezing, tightness of the chest, general feeling of 
being unwell, and dizziness. 
 
If any of these symptoms occur, stop the injection immediately and contact your doctor.  
 
Talk to your doctor if you think that your bleed is not being controlled with the dose you receive, as 
there can be several reasons for this. Some people using this medicine can develop antibodies to factor 
VIII (also known as factor VIII inhibitors). Factor VIII inhibitors make NovoEight less effective in 
preventing or controlling bleeding. If this happens you may need a higher dose of NovoEight or a 
different medicine to control your bleed. Do not increase the total dose of NovoEight to control your 
bleed without talking to your doctor. You should tell your doctor if you have been previously treated 
with factor VIII products, especially if you developed inhibitors, since there might be a higher risk that 
it happens again. 
 
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 NovoEight, tell your doctor immediately. 
 
Other medicines and NovoEight 
Tell your doctor if you are taking, have recently taken or might take any other medicines.  
 
Pregnancy and breastfeeding  
If you are pregnant or breastfeeding, think that you may be pregnant or are planning to have a baby, 
ask your doctor for advice before taking this medicine. 
 
Driving and using machines 
NovoEight has no influence on your ability to drive and use machines. 
 
NovoEight contains sodium 
This medicine contains 30.5 mg sodium (main component of cooking/table salt) per reconstituted vial.  
This is equivalent to 1.5% of the recommended maximum dietary intake of sodium for an adult. 
 
Talk to your doctor if you are on a controlled sodium diet. 
 
 
3. How to use NovoEight 
 
Treatment with NovoEight 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 has told you. Check with your doctor 
if you are not sure. 
 
Your doctor will calculate your dose for you. This will depend on your weight and what the medicine 
is being used for.  
 
Prevention of bleeding 
The usual dose of NovoEight is 20 to 50 international units (IU) per kg of body weight. The injection 
is given every 2 to 3 days. In some cases, especially in younger patients, more frequent injections or 
higher doses may be needed. 
 
Treatment of bleeding 
The dose of NovoEight 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. 
 
Use in children and adolescents 
NovoEight can be used in children of all ages. In children (below the age of 12) higher doses or more 
frequent injections may be needed. Adolescents (above the age of 12) can use the same dose as adults. 



49 

 
How NovoEight is given 
NovoEight is given as an injection into a vein. See ‘Instructions on how to use NovoEight’ for more 
information. 
 
If you use more NovoEight than you should 
If you use more NovoEight than you should, tell your doctor or go to a hospital straight away. 
 
If you forget to use NovoEight 
You should contact your doctor if you have missed a dose and do not know how to compensate for 
this.  
 
If you stop using NovoEight 
If you stop using NovoEight you may no longer be protected against bleeding or a current bleed may 
not stop. Do not stop using NovoEight without talking to your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. The 
following side effects may occur with this medicine. 
 
If severe, sudden allergic reactions (anaphylactic reactions) occur (very rare), the injection must be 
stopped immediately. You must contact your doctor immediately if you have one of the following 
early symptoms: 
 
• difficulty in breathing, shortness of breath or wheezing 
• chest tightness 
• swelling of the lips and tongue 
• rash, hives, weals or generalised itching 
• feeling dizzy or loss of consciousness 
• low blood pressure (having pale and cold skin, fast heartbeat). 
 
Severe symptoms, including difficulty in swallowing or breathing and red or swollen face or hands, 
require prompt emergency treatment. 
 
If you have a severe allergic reaction, your doctor may change your medicine.  
 
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 to 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. 
 
Common side effects (may affect up to 1 in 10 people) 
• blood tests showing changes in the way the liver functions 
• reactions (redness and itching) around the site where you injected the medicine. 
 
Common side effects (may affect up to 1 in 10 people) in patients who have not previously 
treated with Factor VIII medicines 
• blushing of the skin 
• inflammation of vein 
• bleeding into joint spaces 
• bleeding in muscle tissue 
• cough 



50 

• redness around the site where you placed catheter 
• vomiting. 
 
Uncommon side effects (may affect up to 1 in 100 people) 
• feeling tired 
• headache 
• feeling dizzy 
• difficulty sleeping (insomnia) 
• fast heartbeat 
• increased blood pressure 
• rash 
• fever 
• feeling hot 
• stiffness of muscles 
• pain in muscles 
• pain in legs and arms 
• swelling of legs and feet 
• joint disease 
• bruising 
• heart attack. 
 
Side effects in children and adolescents 
The side effects observed in children and adolescents are the same as observed in adults. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. 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 NovoEight 
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date, which is stated after ‘EXP’ on the carton and on the vial 
and the pre-filled syringe labels. 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 NovoEight powder is reconstituted it may be kept at: 
 
• room temperature (≤ 30°C) for a single period no longer than 9 months 
 or 
• above room temperature (30°C up to 40°C) for a single period no longer than 3 months.  
 
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 and the storage temperature on the product carton. 
 
Once you have reconstituted NovoEight it should be used right away. If you cannot use the 
reconstituted NovoEight solution immediately, it should be used within: 
• 24 hours stored at 2°C – 8°C 

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


51 

• 4 hours stored at ≤ 30°C, for product which has been kept for a single period no longer than 
9 months at room temperature (≤30°C) 

• 4 hours stored up to 40°C, for product which has been kept for a single period no longer than 
3 months at above room temperature (30°C up to 40°C). 

 
Store the reconstituted product in the vial. If not used straight away the medicine may no longer be 
sterile and could cause infection. Do not store the solution without your doctor’s advice. 
 
The powder in the vial appears as a white or slightly yellow powder. Do not use the powder if the 
colour has changed. 
 
The reconstituted solution will be clear to slightly opalescent. Do not use this medicine if you notice 
that it is cloudy or contains visible particles. 
 
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 NovoEight contains  
– The active substance is turoctocog alfa (human coagulation factor VIII (rDNA)). Each vial of 

NovoEight contains nominally 250, 500, 1000, 1500, 2000 or 3000 IU turoctocog alfa. 
– The other ingredients are L-histidine, sucrose, polysorbate 80, sodium chloride, L-methionine, 

calcium chloride dihydrate, sodium hydroxide and hydrochloric acid.  
– The ingredients in the solvent are sodium chloride and water for injections. 
 
After reconstitution with the supplied solvent (sodium chloride 9 mg/ml (0.9%) solution for injection), 
the prepared solution for injection contains 62.5, 125, 250, 375, 500 or 750 IU turoctocog alfa per ml, 
respectively, (based on the strength of turoctocog alfa, i.e. 250, 500, 1000, 1500, 2000 or 3000 IU). 
 
What NovoEight looks like and contents of the pack 
NovoEight is a powder and solvent for solution for injection. Each pack of NovoEight contains a vial 
with white or slightly yellow powder, a 4 ml pre-filled syringe with a clear colourless solution, a 
plunger rod and a vial adapter.  
 
Marketing Authorisation Holder and Manufacturer 
Novo Nordisk A/S 
Novo Allé 
DK-2880 Bagsværd, Denmark 
 
 
This leaflet was last revised in  
 
 
Other sources of information  
 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 

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


52 

 
Instructions on how to use NovoEight 
 
READ THESE INSTRUCTIONS CAREFULLY BEFORE USING NOVOEIGHT. 
 
NovoEight is supplied as a powder. Before injection (administration) it must be reconstituted with 
the solvent supplied in the syringe. The solvent is a sodium chloride 9 mg/ml (0.9%) solution. The 
reconstituted NovoEight must be injected into your vein (intravenous injection). The equipment in 
this package is designed to reconstitute and inject NovoEight.  
 
You will also need an infusion set (tubing and butterfly needle), sterile alcohol swabs, gauze pads 
and plasters. These devices are not included in the NovoEight package. 
 
Do not use the equipment without proper training from your doctor or nurse. 
 
Always wash your hands and ensure that the area around you is clean. 
 
When you prepare and inject medicine directly into the veins, it is important to use a clean and 
germ free (aseptic) technique. Improper technique can introduce germs that can infect the blood. 
 
Do not open the equipment until you are ready to use it. 
 
Do not use the equipment if it has been dropped, or if it is damaged. Use a new package instead. 
 
Do not use the equipment if it is expired. Use a new package instead. The expiry date is printed 
after ‘EXP’ on the outer carton, on the vial, on the vial adapter, and on the pre-filled syringe. 
 
Do not use the equipment if you suspect it is contaminated. Use a new package instead. 
 
Do not dispose of any of the items until after you have injected the reconstituted solution. 
 
The equipment is for single use only. 
 
Contents 
 
The package contains: 
 
• 1 vial with NovoEight powder 
• 1 vial adapter 
• 1 pre-filled syringe with solvent  
• 1 plunger rod (placed under the syringe) 
 
 



53 

 

 
Overview 
Vial with NovoEight powder 

Plastic cap 
Rubber stopper 

(under plastic cap) 

 

 

Protective cap 
Vial adapter 

Spike 
(under protective paper) 

Protective 
paper 

 
 
 

 

 

Syringe cap 

Syringe tip 
(under syringe 

cap) 

Pre-filled syringe with solvent 

Scale 

Plunger 

 

 

Thread 

Plunger rod 

Wide top 
end 

 
 
1. Prepare the vial and the syringe 
 
• Take out the number of NovoEight 

packages you need. 
 
• Check the expiry date. 
 
• Check the name, strength and 

colour of the package, to make sure it 
contains the correct product. 

 
• Wash your hands and dry them 

properly using a clean towel or air dry. 
 
• Take the vial, the vial adapter and the 

pre-filled syringe out of the carton. 
Leave the plunger rod untouched in 
the carton. 

 
• Bring the vial and the pre-filled 

syringe to 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 

 
 
 

 

 A 

 



54 

vial and pre-filled syringe. 
• Remove the plastic cap from the vial. 

If the plastic cap is loose or missing, 
do not use the vial. 

 
• Wipe the rubber stopper with a 

sterile alcohol swab and allow it to air 
dry for a few seconds before use to 
ensure that it is as germ free as 
possible. 

 
• Do not touch the rubber stopper 

with your fingers as this can transfer 
germs. 

 

 B 

 
 

2. Attach the vial adapter 
 
• Remove the protective paper from 

the vial adapter. 
 
If the protective paper is not fully 
sealed or if it is broken, do not use 
the vial adapter. 
 
Do not take the vial adapter out of 
the protective cap with your fingers. 
If you touch the spike on the vial 
adapter, germs from your fingers can 
be transferred. 

 
 

 

 C 

 

• Place the vial on a flat and solid 
surface. 
 

• Turn over the protective cap, and 
snap the vial adapter onto the vial. 
 
Once attached, do not remove the 
vial adapter from the vial. 

 

 D 

 
 

• Lightly squeeze the protective cap 
with your thumb and index finger as 
shown. 
 
Remove the protective cap from the 
vial adapter. 
 
Do not lift the vial adapter from the 
vial when removing the protective cap. 

 E 

 

3. Attach the plunger rod and the syringe 
 
• Grasp the plunger rod by the wide top 

end and take it out of the carton. Do 
not touch the sides or the thread of 
the plunger rod. If you touch the 
sides or the thread, germs from your 
fingers can be transferred. 

 
• Immediately connect the plunger rod 

to the syringe by turning it clockwise 

 
 

 

 F 

 



55 

into the plunger inside the pre-filled 
syringe until resistance is felt. 

• Remove the syringe cap from the pre-
filled syringe by bending it down until 
the perforation breaks. 

 
• Do not touch the syringe tip under 

the syringe cap. If you touch the 
syringe tip, germs from your fingers 
can be transferred. 

 
If the syringe cap is loose or missing, 
do not use the pre-filled syringe. 

 

 G 

 

• Screw the pre-filled syringe securely 
onto the vial adapter until resistance is 
felt. 

 

 H 

 
 

4. Reconstitute the powder with the 
solvent 
 
• Hold the pre-filled syringe slightly 

tilted with the vial pointing 
downwards. 

 
• Push the plunger rod to inject all the 

solvent into the vial. 

 

 I 

 

• Keep the plunger rod pressed down 
and swirl the vial gently until all the 
powder is dissolved. 
 
Do not shake the vial as this will 
cause foaming. 
 

• Check the reconstituted solution. It 
must be clear to slightly opalescent 
(slightly unclear). If you notice visible 
particles or discolouration, do not 
use it. Use a new package instead. 

 

 J 

 
NovoEight is recommended to be used immediately after it has been reconstituted. This is 
because if left, the medicine may no longer be sterile and could cause infections. 
 
If you cannot use the reconstituted NovoEight solution immediately, it should be used within 
4 hours when stored at room temperature or up to 40°C and within 24 hours when stored at 2°C – 
8°C. Store the reconstituted product in the vial. 
 
Do not freeze reconstituted NovoEight solution or store it in syringes. 
Do not store the solution without your doctor’s advice. 
 
Keep reconstituted NovoEight solution out of direct light. 
 



56 

 
If your dose requires more than one vial, repeat steps A to J with additional vials, vial adapters and 
pre-filled syringes until you have reached your required dose. 
 
• Keep the plunger rod pushed 

completely in. 
 
• Turn the syringe with the vial upside 

down. 
 
• Stop pushing the plunger rod and let 

it move back on its own while the 
reconstituted solution fills the syringe. 

 
• Pull the plunger rod slightly 

downwards to draw the reconstituted 
solution into the syringe. 

 
• In case you only need part of the 

entire vial, use the scale on the 
syringe to see how much 
reconstituted solution you withdraw, 
as instructed by your doctor or 
nurse. 
 
If, at any point, there is too much air in 
the syringe, inject the air back into the 
vial. 

 
• While holding the vial upside down, 

tap the syringe gently to let any air 
bubbles rise to the top. 

 
• Push the plunger rod slowly until all 

air bubbles are gone. 
 
 

 

 K 

 

• Unscrew the vial adapter with the 
vial. 

 
• Do not touch the syringe tip. If you 

touch the syringe tip, germs from your 
fingers can be transferred. 

 

 

 L 

 
5. Inject the reconstituted solution 
 
NovoEight is now ready to be injected into your vein. 
 
• Inject the reconstituted solution as instructed by your doctor or nurse. 
 
• Inject slowly over 2 to 5 minutes. 
 
• Do not mix NovoEight with any other intravenous infusions or medicines. 
 
Injecting NovoEight via needleless connectors for intravenous (IV) catheters  
 
Caution: The pre-filled syringe is made of glass and is designed to be compatible with standard 



57 

luer-lock connections. Some needleless connectors with an internal spike are incompatible with the 
pre-filled syringe. This incompatibility may prevent administration of the medicine and/or result in 
damage to the needleless connector. 
 
Injecting the solution via a central venous access device (CVAD) such as a central venous catheter 
or a subcutaneous port: 
• Use a clean and germ free (aseptic) technique. Follow the instructions for proper use for your 
connector and CVAD in consultation with your doctor or nurse. 
• Injecting into a CVAD may require using a sterile 10 ml plastic syringe for withdrawal of the 
reconstituted solution. This should be done right after step J. 
• If the CVAD line needs to be flushed before or after NovoEight injection, use sodium chloride 
9 mg/ml solution for injection. 
 
 
Disposal 
 
• After injection, safely dispose of all 

unused NovoEight solution, the 
syringe with the infusion set, the vial 
with the vial adapter and other waste 
materials as instructed by your 
pharmacist. 
 
Do not throw it out with the ordinary 
household waste. 

 

 

 M 

 

 
Do not disassemble the equipment before disposal.  
 
Do not reuse the equipment. 

 


	ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET