Esperoct

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 
Esperoct 500 IU powder and solvent for solution for injection 
Esperoct 1000 IU powder and solvent for solution for injection 
Esperoct 1500 IU powder and solvent for solution for injection 
Esperoct 2000 IU powder and solvent for solution for injection 
Esperoct 3000 IU powder and solvent for solution for injection. 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Esperoct 500 IU powder and solvent for solution for injection 
Each powder vial contains nominally 500 IU turoctocog alfa pegol*. 
After reconstitution, 1 mL of solution contains approximately 125 IU turoctocog alfa pegol. 
 
Esperoct 1000 IU powder and solvent for solution for injection 
Each powder vial contains nominally 1000 IU turoctocog alfa pegol*. 
After reconstitution, 1 mL of solution contains approximately 250 IU turoctocog alfa pegol. 
 
Esperoct 1500 IU powder and solvent for solution for injection 
Each powder vial contains nominally 1500 IU turoctocog alfa pegol*. 
After reconstitution, 1 mL of solution contains approximately 375 IU turoctocog alfa pegol. 
 
Esperoct 2000 IU powder and solvent for solution for injection 
Each powder vial contains nominally 2000 IU turoctocog alfa pegol*. 
After reconstitution, 1 mL of solution contains approximately 500 IU turoctocog alfa pegol. 
 
Esperoct 3000 IU powder and solvent for solution for injection 
Each powder vial contains nominally 3000 IU turoctocog alfa pegol*. 
After reconstitution, 1 mL of solution contains approximately 750 IU turoctocog alfa pegol. 
 
The potency (IU) is determined using the European Pharmacopoeia chromogenic assay. The specific 
activity of turoctocog alfa pegol is approximately 9500 IU/mg protein. 
 
The active substance turoctocog alfa pegol is a covalent conjugate of the protein turoctocog alfa* with 
a 40 kDa polyethylene-glycol (PEG). 
 
*Human factor VIII, produced by recombinant DNA technology in a Chinese Hamster Ovary (CHO) 
cell line, and no additives of human or animal origin are used in the cell culture, purification, 
conjugation or formulation of Esperoct. 
 
Excipient with known effect 
 
Each reconstituted vial contains 30.5 mg of sodium (see section 4.4). 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection. 
 



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The powder is white to off-white. 
 
The solvent is clear and colourless. 
 
pH: 6.9. 
 
Osmolality: 590 mOsmol/kg. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment and prophylaxis of bleeding in patients 12 years and above with haemophilia A (congenital 
factor VIII deficiency). 
 
4.2 Posology and method of administration 
 
Treatment should be initiated under the supervision of a physician experienced in the treatment of 
haemophilia. 
 
Previously untreated patients 
 
The safety and efficacy of Esperoct in previously untreated patients have not yet been established. 
 
Treatment monitoring 
 
During the course of treatment, appropriate determination of factor VIII activity levels is advised to 
guide adjustments of the dosing regimen of Esperoct, if needed. Individual patients may vary in their 
response to factor VIII, demonstrating different half-lives and incremental recoveries. Dose based on 
bodyweight may require adjustment in underweight or overweight patients. In the case of major 
surgical interventions in particular, monitoring of the factor VIII substitution therapy by measurement 
of plasma factor VIII activity is necessary. 
 
The factor VIII activity of Esperoct can be measured using the conventional factor VIII assays, the 
chromogenic assay and the one-stage assay.  
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.  
When using a one-stage clotting assay some silica based reagents should be avoided as they cause 
underestimation. 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, dosing interval and duration of the substitution therapy depend on the severity of the 
factor VIII deficiency, on the location and extent of the bleeding, on the targeted factor VIII activity 
level and the patient’s clinical condition. The number of units of factor VIII administered is expressed 
in International Units (IU), which is related to the current WHO concentrate standard for factor VIII 
products. The activity of factor VIII in plasma is expressed either as percentage (relative to normal 
human plasma level) or in International Units per dL (relative to the current 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 
of human plasma. 
 



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On demand treatment and treatment of bleeding episodes 
 
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 (IU) = 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. 
 
Guidance for the dosing of Esperoct for the on-demand treatment and treatment of bleeding episodes 
is provided in table 1. Plasma factor VIII activity levels should be maintained at or above the 
described plasma levels (in IU per dL or % of normal). For treatment of bleeds a maximum single 
dose of Esperoct at 75 IU/kg and a maximum total dose of 200 IU/kg/24 hours may be administered. 
 
Table 1 Guidance for treatment of bleeding episodes with Esperoct 

Degree of haemorrhage Factor VIII level 
required (IU/dL 
or % of 
normal)a  

Frequency of 
doses (hours) 

Duration of therapy 

Mild 
Early haemarthrosis, mild 
muscle bleeding or mild 
oral bleeding 

20-40 12-24 Until the bleeding is resolved 

Moderate 
More extensive 
haemarthrosis, muscle 
bleeding, haematoma 

30-60 12-24 Until the bleeding is resolved 

Severe or 
life-threatening 
haemorrhages 

60-100 8-24 Until the threat is resolved 
 
 

a The required dose is determined using the following formula: 
Required units (IU) = body weight (kg) x desired factor VIII rise (%) (IU/dL) x 0.5 (IU/kg per IU/dL). 
 
Perioperative management 
 
The dose level and dosing intervals for surgery depend on the procedure and local practice. A 
maximum single dose of Esperoct at 75 IU/kg and a maximum total dose of 200 IU/kg/24 hours may 
be administered. 
The frequency of doses and duration of therapy should always be individually adjusted based on 
individual clinical response. 
 
Table 2 includes general recommendation for dosing of Esperoct for perioperative management. 
Consideration should be given to maintain a factor VIII activity at or above the target range. 
 
Table 2 Guidance for dosing of Esperoct for perioperative management 

Type of surgical 
procedure 

Factor VIII 
level required 
(%) (IU/dL)a  

Frequency of doses (hours) Duration of therapy 

Minor surgery 
Including tooth 
extraction 

30-60 Within one hour before 
surgery 
 

Single dose or repeat injection 
every 24 hours for at least 1 day 
until healing is achieved 



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Repeat after 24 hours if 
necessary 

Major surgery 80-100 
(pre- and 
post-operative) 

Within one hour before 
surgery to achieve factor VIII 
activity within the target 
range 
 
Repeat every 8 to 24 hours to 
maintain factor VIII activity 
within the target range 

Repeat injection every 8 to 
24 hours as necessary until 
adequate wound healing is 
achieved 
 
Consider to continue therapy for 
another 7 days to maintain a 
factor VIII activity of 30% to 
60% (IU/dL) 

a The required dose is determined using the following formula: 
Required units (IU) = body weight (kg) x desired factor VIII rise (%) (IU/dL) x 0.5 (IU/kg per IU/dL). 
 
Prophylaxis 
The recommended starting dose is 50 IU of Esperoct per kg body weight every 4 days. 
 
The maximum single dose is 75 IU/kg. 
 
Adjustments of doses and administration intervals may be considered based on achieved factor VIII 
levels and individual bleeding tendency. 
 
Paediatric population 
The dose in adolescents (12 years and above) is the same as for adults. 
In children below 12 years long-term safety has not been established. 
 
Method of administration 
 
Esperoct is for intravenous use. 
 
Esperoct should be administered by intravenous injection (over approximately 2 minutes) after 
reconstitution of the powder with 4 mL supplied solvent (sodium chloride 9 mg/mL (0.9%) solution 
for injection). 
 
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 protein. 
 
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 administraered product should be clearly recorded. 
 
Hypersensitivity 
 
Allergic-type hypersensitivity reactions are possible with Esperoct. 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 immediately discontinue the use of the medicinal product 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. 
 



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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 pro-coagulant 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 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 factor VIII may increase 
the cardiovascular risk. 
 
Catheter-related complications 
 
If a central venous access device (CVAD) is required, the risk of CVAD-related complications 
including local infections, bacteraemia and catheter site thrombosis should be considered. 
 
Paediatric population 
 
The listed warnings and precautions apply both to adults and adolescents (12-18 years). 
 
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 2.0 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) with other medicinal products have been 
reported. 
 
4.6 Fertility, pregnancy and lactation 
 
Animal reproduction studies have not been conducted with factor VIII. 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, factor VIII should be used during pregnancy and lactation 
only if clearly indicated. 
 
4.7 Effects on ability to drive and use machines 
 
Esperoct has no influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 



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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 Esperoct. 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 
 
The frequencies of adverse reactions as observed in 270 unique subjects across five prospective, 
multi-centre clinical studies in previously treated patients (PTPs) with severe haemophilia A (<1% 
endogenous factor VIII activity) and no history of inhibitors are listed in table 3. The categories of 
adverse reactions presented in table 3 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). 
 
Table 3  Frequency of adverse reactions in clinical trials for PTPs* 

MedDRA System Organ Class Adverse reactions Frequency 

Blood and lymphatic system disorders Factor VIII inhibition Uncommon (PTPs)** 

Immune system disorders Hypersensitivity Uncommon 

Skin and subcutaneous tissue disorders Rash 
Erythema 
Pruritus 

Common 

General disorders and administration sites 
conditions 

Injection site reactions*** Common 

* PTPs: Previously-treated patients. 
** Frequency is based on studies with all factor VIII products which included patients with severe haemophilia A. 
*** Preferred terms included in injection site reactions: Injection site reaction, Vessel puncture site haematoma, Infusion site reaction, 
Injection site erythema, Injection site rash, Vessel puncture site pain, and Injection site swelling. 
 
Description of selected adverse reactions 
 
Factor VIII inhibitors 
One confirmed case of factor VIII inhibitor occurred in an 18 year-old previously treated patient on 
prophylactic treatment with Esperoct. The patient had a factor VIII gene intron 22 inversion and was at 
a high risk of developing factor VIII inhibitors.  
There is no indication of an increased risk of factor VIII inhibitor development with treatment of 
Esperoct as compared to other factor VIII products. 
 
Anti-drug antibodies 
There was one case of persistent anti-drug antibodies concomitant with the confirmed case of factor VIII 
inhibitors (see Factor VIII inhibitors). Three patients had transiently positive test results for anti-drug 
antibodies after administration of Esperoct but no correlation with adverse events could be established. 



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Anti-PEG antibodies 
Thirty-two patients had pre-existing anti-PEG antibodies before administration of Esperoct. Twenty of 
the 32 patients were negative for anti-PEG antibodies post administration of Esperoct. Eleven patients 
developed transient low titre anti-PEG antibodies. No correlation with adverse events could be 
established. 
 
Paediatric population 
 
No difference in the safety profile was observed between previously treated adolescents (12-18 years) 
and adult patients. 
 
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: antihemorrhagics, blood coagulation factor VIII, ATC code: B02BD02. 
 
Mechanism of action 
 
Turoctocog alfa pegol is a purified recombinant human factor VIII (rFVIII) product with a 40 kDa 
polyethylene-glycol (PEG) conjugated to the protein. The PEG is attached to the O-linked glycan in 
the truncated B-domain of rFVIII (turoctocog alfa). The mechanism of action of turoctocog alfa pegol 
is based on the replacement of the deficient or absent factor VIII in patients with haemophilia A. 
When turoctocog alfa pegol is activated by thrombin at the site of injury, the B-domain containing the 
PEG moiety and the a3-region are cleaved off, thus generating activated recombinant factor VIII 
(rFVIIIa) which is similar in structure to native factor VIIIa. 
The factor VIII/von Willebrand factor complex consists of two molecules (factor VIII and von 
Willebrand factor) with different physiological functions. When injected into a haemophiliac patient, 
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 factor VIII replacement 
therapy the plasma levels of factor VIII are increased, thereby enabling a temporary correction of the 
factor deficiency and correction of the bleeding tendencies. 
 
Clinical efficacy during prophylaxis and treatment of bleeding episodes 
 

The clinical efficacy of Esperoct for prophylaxis and treatment of bleeds was investigated in five 
prospective, multi-centre clinical studies in 270 previously treated patients (PTPs) with severe 
haemophilia A. 

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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Prophylaxis in adults/adolescents 
 
The efficacy of Esperoct for prophylaxis and treatment of bleeds was evaluated in an open-label, 
non-controlled trial in adolescents and adult patients with severe haemophilia A ages 12 years and 
above. The prophylactic effect of Esperoct was demonstrated with a dosing at 50 IU per kg body 
weight every 4 days or every 3–4 days (twice weekly) in 175 patients. The median annualised 
bleeding rate (ABR) in adults and adolescents receiving Esperoct was 1.18 (Interquartile range IQR: 
0.00;4.25), whereas the spontaneous ABR was 0.00 (IQR: 0.00;1.82), traumatic ABR was 0.00 (IQR: 
0.00;1.74) and joint ABR was 0.85 (IQR: 0.00;2.84). When including imputations, (replacing missing 
data for withdrawn patients with a substituted value) the estimated mean ABR for all bleeds was 
3.70 (95% CI: 2.94;4.66). Of the 175 adults/adolescents on prophylaxis, 70 (40%) did not have any 
bleeds. The mean annual consumption for prophylaxis was 4641 IU/kg. 
 
Of note, annualized bleeding rate (ABR) is not comparable between different factor concentrates and  
between different clinical studies. 
 
Adults/adolescents who had a low bleeding rate of 0-2 bleeding episodes during the last 6 months and 
had obtained at least 50 doses of Esperoct had the option of being randomised to prophylaxis treatment 
every 7 days (75 IU/kg every 7 days) or every 4 days (50 IU/kg every 4 days). A total of 55 of the 120 
eligible patients chose to be randomised (17 to the every 4 days dosing and 38 to the 75 IU every 
7 days). The ABR for randomised patients was 1.77 (0.59; 5.32) for treatment every 4 days and 3.57 
(2.13; 6.00) for once weekly prophylaxis. Nine of these patients reverted back to prophylaxis every 
4 days during the randomised study phase. Overall, including all extensions parts, 31 of 61 patients on 
every 7 days prophylaxis switched back to every 4 days treatment. 
 
Prophylaxis in children (below 12 years) 
 
The use of Esperoct in children below 12 years is not indicated (see section 4.2 for information on 
paediatric use). 
The efficacy and safety of Esperoct for prophylaxis treatment of bleeds were evaluated in an 
open-label, single-arm, non-controlled trial in 68 children below 12 years with severe haemophilia A. 
The prophylactic effect of Esperoct was demonstrated with a dosing at 60 IU per kg body weight 
(50-75 IU/kg) twice weekly. The median and estimated mean annualised bleeding rate in children 
below 12 years receiving Esperoct twice weekly was 1.95 and 2.13 (95% CI: 1.48;3.06), whereas the 
spontaneous ABR was 0.00 and 0.58 (95% CI: 0.24;1.40), traumatic ABR was 0.00 and 1.52 (95% CI: 
1.07;2.17) and joint ABR was 0.00 and 1.03 (95% CI: 0.59;1.81), respectively. Of the 68 children 
below 12 years on prophylaxis, 29 (42.6%) did not have any bleeds. 
The mean annual consumption for prophylaxis was 6475 IU/kg. 
 
Clinical efficacy of Esperoct in treatment of bleeding episodes and during on-demand treatment 
 
The efficacy of Esperoct in the treatment of bleeding episodes was demonstrated in all age groups. 
The vast majority of bleeds treated with Esperoct were of mild/moderate severity. 
The overall success rate for the treatment of bleeds was 87.7% and 94.4% of all bleeds treated with 
1-2 injections. 
 
In 12 patients above 18 years of age, 1,126 bleedings were treated among patients receiving 
on-demand treatment with an average treatment dose of 38.1 IU/kg with a mean annual consumption 
of 1457 IU/kg. Of the total 1,126 bleeds, 86.9% were effectively treated with 1 injection and 96.8% 
were effectively treated with 1-2 injections of Esperoct. 
 
Clinical efficacy of Esperoct during major surgery 
 
Esperoct was effective in maintaining haemostasis during major surgery with a success rate of 95.6% 
in all major surgeries performed (43 out of 45 had the effect rated as ‘excellent‘ or ‘good‘). 
 
5.2 Pharmacokinetic properties 



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In total, 129 single-dose pharmacokinetic (PK) profiles of Esperoct were evaluated in 86 patients 
(including 24 paediatric patients of 0 to below 12 years). 
 
All pharmacokinetic studies with Esperoct were conducted in previously treated patients with severe 
haemophilia A (factor VIII <1%). Patients received a single dose of 50 IU/kg, and blood samples were 
collected prior to dosing and at multiple time points up to 96 hours after dosing. 
 
The half-life of Esperoct was 1.6 fold longer compared to unmodified factor VIII products in adults. 
 
Pharmacokinetic parameters 
 
A total of 108 single dose pharmacokinetic profiles at 50 IU/kg Esperoct were evaluated in 
69 patients. The single dose pharmacokinetic parameters are comparable between young children (0 to 
below 6 years) and older children (6 to below 12 years), and between adolescents (12 to17 years) and 
adults (18 years and above). 
As expected incremental recovery appeared to be lower while body weight adjusted clearance 
appeared to be higher in children compared to adults and adolescents. In general, there was a trend of 
increasing incremental recovery and decreasing clearance (mL/h/kg) with age. This corresponds to a 
higher volume of distribution per kilo body weight in children compared to adults (table 4). 
The single dose pharmacokinetic parameters determined after 28 weeks of prophylactic treatment with 
Esperoct were consistent with the initial pharmacokinetic parameters. 
 
Single-dose pharmacokinetic parameters of Esperoct are listed in table 4. The use of Esperoct in 
children below 12 years is not indicated. 
 
Table 4 Single-dose pharmacokinetic parameters of Esperoct 50 IU/kg in children, 

adolescents and adults by age using the chromogenic assay (geometric mean 
[CV%]) 

PK Parameter 
N=No. of patients 

0 to below 6 years 
N=13 

6 to below 12 years 
N=11 

12 to 
below18 years 

N=3 

18 years and above 
N=42 

Number of profiles 13 11 5 79 

IR (IU/dL) per 
(IU/kg)a 

1.80 (29) 1.99 (25) 2.79 (12) 2.63 (22) 

Maximum 
factor VIII activity 
(IU/dL)a 

101.2 (28) 119.6 (25) 133.2 (9) 134.4 (23) 

t1/2 (hours) 13.6 (20) 14.2 (26) 15.8 (43) 19.9 (34) 

AUCinf 
(IU*hour/dL) 

2147 (47) 2503 (42) 3100 (44) 3686 (35) 

CL (mL/hour/kg) 2.6 (45) 2.4 (40) 1.5 (43) 1.4 (32) 

Vss (mL/kg) 44.2 (34) 41.2 (25) 33.4 (10) 37.7 (27) 

MRT (hours) 17.0 (22) 17.3 (31) 21.7 (45) 25.2 (29)b 
Abbreviations: AUC = area under the factor VIII activity time profile; t1/2 = terminal half-life; MRT = mean residence time; CL = clearance; 
Vss = volume of distribution at steady–state; IR = Incremental recovery. 
a Incremental recovery and factor VIII were assessed 30 min post-dosing for patients 12 years and above and 60 min post-dosing (first 
sample) for children below12 years. 
b Calculation based on 67 profiles. 
 
The mean trough plasma factor VIII activity levels at steady–state during prophylactic treatment with 
Esperoct dosed with 50 IU/kg every 4 days is 3.0 IU/dL (95% CI: 2.6;3.4) in patients 12 years and 
above. 



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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 or reconstituted with injection solutions other than the provided sodium chloride solvent. 
 
The reconstituted product should not be administered in the same tubing or container with other 
medicinal products. 
 
6.3 Shelf life 
 
Unopened vial (before reconstitution): 
 
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 12 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 stored outside of the refrigerator, the product must not be returned for 
storage in the refrigerator.  
 
Record the beginning of storage outside refrigerator and the storage temperature in the space provided 
on the carton. 
 
After reconstitution 
 
Chemical and physical in-use stability have been demonstrated for: 
• 24 hours when stored in a refrigerator (2°C - 8°C) or 
• 4 hours at ≤30°C or 



12 

• 1 hour between ˃30°C and 40°C, only if the product was stored above room temperature 
(˃30°C up to 40°C) before reconstitution for no longer than 3 months. 

 
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 
users and would normally not be recommended for longer than as stated above, unless reconstitution 
has taken place in controlled and validated aseptic conditions.  
 
The reconstituted solution should be stored in the vial. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. 
Store in the original package 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 Esperoct contains: 
– 1 glass vial (type I) with powder closed with a chlorobutyl rubber stopper, an aluminium seal 

with a plastic snap-off cap 
– 1 sterile vial adapter for reconstitution 
– 1 pre-filled syringe of 4 mL solvent with backstop (polypropylene), a rubber plunger 

(bromobutyl) and a rubber tip cap (bromobutyl) 
– 1 plunger rod (polypropylene). 
 
6.6 Special precautions for disposal and other handling 
 
Esperoct 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 and colourless liquid free of 
visible particles. The reconstituted medicinal product should be inspected visually for particulate 
matter and discolouration prior to administration. The solution should be clear and colourless. Do not 
use solutions that are cloudy or have deposits. 
 
For instructions on reconstitution of the medicinal product before administration, see the package 
leaflet. 
 
The rate of administration should be determined by the patient’s comfort level over approximately 
2 minutes. 
 
An infusion set (butterfly needle with tubing), sterile alcohol swabs, gauze pads and plasters will also 
be needed. These devices are not included in the Esperoct package. 
 
Always use an aseptic technique. 
 
Disposal 
 
After the injection, safely dispose of the syringe with the infusion set and the vial with the vial adapter. 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Novo Nordisk A/S 



13 

Novo Allé 
DK-2880 Bagsværd 
Denmark 
 
 
8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/19/1374/001 
EU/1/19/1374/002 
EU/1/19/1374/003 
EU/1/19/1374/004 
EU/1/19/1374/005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 20 June 2019 
 
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/


14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER 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 



15 

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

 
Name and address of the manufacturer of the biological active substance 
 
Novo Nordisk US Bio Production Inc. 
9 Technology Drive 
West Lebanon 
New Hampshire 
03784 
United States 
 
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 (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal. 
The marketing authorisation holder shall submit the first periodic safety update report for this product 
within 6 months following authorisation. 
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP. 
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.  

 
• Obligation to conduct post-authorisation measures 
 
The MAH shall complete, within the stated timeframe, the below measures: 
 
Description Due date 



16 

Post-authorisation safety study (PASS): In order to investigate the potential effects of 
PEG accumulation in the choroid plexus of the brain and other tissues/organs, the MAH 
should conduct and submit the results of a post-authorisation safety study according to an 
agreed protocol. 

31/12/2027 

  



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
A. LABELLING 



19 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esperoct 500 IU powder and solvent for solution for injection 
 
turoctocog alfa Pegol 
(recombinant coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Powder: 500 IU turoctocog alfa pegol (approx. 125 IU/mL 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 a pre-filled syringe, 1 plunger rod and 1 vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use 
 
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 WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



20 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze 
 
During the shelf life, the product may be stored  
• at room temperature (≤30°C) for a single period no longer than 12 months or 
• above room temperature (>30°C - 40°C) for a single period no longer than 3 months 
 
Date removed from refrigerator: ____________ Stored at ≤30°C  or >30°C - 40°C   
 
Store in the original package 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 NUMBER 
 
EU/1/19/1374/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Esperoct 500 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 

    



21 

SN 
NN 



22 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Esperoct 500 IU powder for solution for injection 
turoctocog alfa Pegol 
IV 
 
 
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 



23 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esperoct 1000 IU powder and solvent for solution for injection 
 
turoctocog alfa Pegol 
(recombinant coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Powder: 1000 IU turoctocog alfa pegol (approx. 250 IU/mL 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 a pre-filled syringe, 1 plunger rod and 1 vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use 
 
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 WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



24 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze 
 
During the shelf life, the product may be stored 
• at room temperature (≤30°C) for a single period no longer than 12 months or 
• above room temperature (>30°C - 40°C) for a single period no longer than 3 months 
 
Date removed from refrigerator:___________________Stored at ≤30°C  or >30°C - 40°C   
 
Store in the original package 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 NUMBER 
 
EU/1/19/1374/002 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Esperoct 1000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 

    



25 

SN 
NN 



26 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Esperoct 1000 IU powder for solution for injection 
turoctocog alfa Pegol 
IV 
 
 
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 



27 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esperoct 1500 IU powder and solvent for solution for injection 
 
turoctocog alfa Pegol 
(recombinant coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Powder: 1500 IU turoctocog alfa pegol (approx. 375 IU/mL 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 a pre-filled syringe, 1 plunger rod and 1 vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use 
 
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 WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



28 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze 
 
During the shelf life, the product may be stored  
• at room temperature (≤30°C) for a single period no longer than 12 months or 
• above room temperature (>30°C - 40°C) for a single period no longer than 3 months 
 
Date removed from refrigerator: ____________ Stored at ≤30°C  or >30°C - 40°C   
 
Store in the original package 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/1/19/1374/003 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Esperoct 1500 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 

    



29 

SN 
NN 



30 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Esperoct 1500 IU powder for solution for injection 
turoctocog alfa Pegol 
IV 
 
 
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 



31 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esperoct 2000 IU powder and solvent for solution for injection 
 
turoctocog alfa Pegol 
(recombinant coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Powder: 2000 IU turoctocog alfa pegol (approx. 500 IU/mL 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 a pre-filled syringe, 1 plunger rod and 1 vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use 
 
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 WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



32 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze 
 
During the shelf life, the product may be stored  
• at room temperature (≤30°C) for a single period no longer than 12 months or  
• above room temperature (>30°C - 40°C) for a single period no longer than 3 months 
 
Date removed from refrigerator: ____________ Stored at ≤30°C  or >30°C - 40°C   
 
Store in the original package 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/1/19/1374/004 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Esperoct 2000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 

    



33 

SN 
NN 



34 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Esperoct 2000 IU powder for solution for injection 
turoctocog alfa Pegol 
IV 
 
 
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 



35 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Esperoct 3000 IU powder and solvent for solution for injection 
 
turoctocog alfa Pegol 
(recombinant coagulation factor VIII) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE 
 
Powder: 3000 IU turoctocog alfa pegol (approx. 750 IU/mL 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 a pre-filled syringe, 1 plunger rod and 1 vial adapter 
 
 
5. METHOD AND ROUTE OF ADMINISTRATION 
 
Read the package leaflet before use 
 
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 WARNINGS, IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 



36 

9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. Do not freeze 
 
During the shelf life, the product may be stored 
• at room temperature (≤30°C) for a single period no longer than 12 months or 
• above room temperature (>30°C - 40°C) for a single period no longer than 3 months 
 
Date removed from refrigerator: ____________ Stored at ≤30°C  or >30°C - 40°C   
 
Store in the original package 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/1/19/1374/005 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Esperoct 3000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 

    



37 

SN 
NN 



38 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Esperoct 3000 IU powder for solution for injection 
turoctocog alfa Pegol 
IV 
 
 
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 



39 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Esperoct 
 
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 
  



40 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
  



41 

Package leaflet: Information for the user 
 

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

 
turoctocog alfa pegol (pegylated human coagulation factor VIII (rDNA)) 

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

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
– Keep this leaflet. You may need to read it again. 
– If you have any further questions, ask your doctor. 
– This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours. 
– If you get any side effects, talk to your doctor. This includes any possible side effects not listed 

in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Esperoct is and what it is used for 
2. What you need to know before you use Esperoct 
3. How to use Esperoct 
4. Possible side effects 
5. How to store Esperoct 
6. Contents of the pack and other information 
 
 
1. What Esperoct is and what it is used for 
 
What Esperoct is 
Esperoct contains the active substance turoctocog alfa pegol and is a long-acting recombinant 
coagulation factor VIII product. Factor VIII is a protein found in the blood that helps to prevent and 
stop bleeding. 
 
What Esperoct is used for 
Esperoct is used to treat and prevent bleeding in people 12 years and above with haemophilia A 
(inborn factor VIII deficiency). 
 
In people with haemophilia A, factor VIII is missing or does not work properly. Esperoct 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 Esperoct 
 
Do not use Esperoct 
• 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 Esperoct if either of the above applies to you. If you are not sure, talk to your doctor before 
using this medicine. 



42 

 
Warnings and precautions 
 
Previous use of factor VIII medicine 
Tell your doctor if you have used factor VIII medicines before, especially if you developed inhibitors 
(antibodies) against the medicine, since there might be a risk that it happens again. 
 
Allergic reactions 
There is a risk that you may experience a severe and sudden allergic reaction (e.g. anaphylactic 
reaction) to Esperoct. 
 
Stop the injection and contact your doctor or an emergency unit immediately if you have early signs of 
allergic reactions. These early signs may include rash, hives, weals, itching on large areas of skin, 
redness and/or swelling of lips, tongue, face or hands, difficulty in swallowing or breathing, wheezing, 
tightness of the chest, pale and cold skin, fast heartbeat, or dizziness, headache, nausea and vomiting. 
 
Development of ‘FVIII inhibitors’ (antibodies) 
Inhibitors (antibodies) can develop during the treatment with all factor VIII medicines 
• These inhibitors, especially at high levels, stop the treatment working properly 
• You will be monitored carefully for development of these inhibitors 
• If your bleeding is not being controlled with Esperoct, tell your doctor immediately 
• Do not increase the total dose of Esperoct to control your bleed without talking to your doctor. 
 
Catheter-related problems 
If you have a catheter where medicines can be injected into your blood (central venous access device), 
you may develop infections or blood clots at the site of the catheter. 
 
Heart disease 
Talk to your doctor or pharmacist if you have heart disease or you are at risk of heart disease. 
 
Children 
Esperoct can not be used in children below 12 years of age. 
 
Other medicines and Esperoct 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before taking this medicine. 
 
Driving and using machines 
Esperoct has no influence on your ability to drive and use machines. 
 
Esperoct 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 daily dietary intake of sodium for an adult. 
 
 
3. How to use Esperoct 
 
Treatment with Esperoct will be started by a doctor who is experienced in the care of people with 
haemophilia A. 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure about how to use Esperoct. 
 
How Esperoct is given 



43 

Esperoct is given as an injection into a vein (intravenously), see “Instructions on how to use Esperoct” 
for more information. 
 
How much to use 
Your doctor will calculate your dose for you. This will depend on your body weight and whether it is 
used to prevent or to treat a bleeding. 
 
To prevent bleeding 
Adults and adolescents (12 years of age and above): The recommended starting dose is 50 IU of 
Esperoct per kg body weight every 4 days. Your doctor may choose another dose or how often the 
injections should be given, based on your need. 
 
To treat bleeding 
The dose of Esperoct 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. If you 
experience that the effect of Esperoct is insufficient, talk to your doctor. 
 
Use in children and adolescents 
Adolescents (12 years of age and above) can use the same dose as adults. 
 
If you use more Esperoct than you should 
If you use more Esperoct than you should, contact your doctor straight away. 
 
If you have to significantly increase your usage of Esperoct to stop a bleed, talk to your doctor 
immediately. For further information, see “Development of ‘FVIII inhibitors’ (antibodies)” in section 
2. 
 
If you forget to use Esperoct 
If you forget a dose, inject the missed dose as soon as you remember. Do not inject a double dose to 
make up for a forgotten dose. Proceed with the next injection as scheduled and continue as advised by 
your doctor. If you are in doubt, contact your doctor. 
 
If you stop using Esperoct 
Do not stop using Esperoct without talking to your doctor. 
If you stop using Esperoct, you may no longer be protected against bleeding or a current bleed may not 
stop. 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. 
 
Allergic reactions (hypersensitivity) 
Stop the injection immediately if you develop severe and sudden allergic reactions (anaphylactic 
reactions). You must contact your doctor or an emergency unit immediately if you have signs of an 
allergic reaction such as: 
• difficulty in swallowing or breathing 
• wheezing 
• chest tightness 
• redness and/or swelling of the lips, tongue, face or hands 
• rash, hives, weals or itching 
• pale and cold skin, fast heartbeat, or dizziness (low blood pressure) 
• headache, nausea or vomiting. 
 
Development of ‘FVIII inhibitors’ (antibodies) 
If you have previously received more than 150 days of treatment with factor VIII, inhibitors 
(antibodies) may develop (may affect up to 1 in 100 people). If this happens, your medicine may stop 



44 

working properly and you may experience persistent bleeding. If this happens, you should contact 
your doctor immediately. See “Development of ‘FVIII inhibitors’ (antibodies)” in section 2. 
 
The following side effects have been observed with Esperoct 
 
Common side effects (may affect up to 1 in 10 people) 
• skin reactions where the injection is given 
• itching (pruritus) 
• redness of skin (erythema) 
• rash. 
 
Uncommon side effects (may affect up to 1 in 100 people) 
• allergic reactions (hypersensitivity). These may become severe and could be life-threatening, see 

“Allergic reactions (hypersensitivity)” above for more information 
• factor VIII inhibitors (antibodies) in patients previously treated with factor VIII. 
 
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 Esperoct 
 
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, on the vial, 
and on the pre-filled syringe labels. The expiry date refers to the last day of that month. 
 
Before reconstitution (before the powder is mixed with the solvent): 
Store in a refrigerator (2°C - 8°C). Esperoct can be kept  
• at room temperature (≤30°C) for a single period for up to 12 months within the shelf life of the 

product or 
• above room temperature (>30°C up to 40°C) for a single period for up to 3 months within the 

shelf life of the product. 
 
When you start to store Esperoct outside the refrigerator, record the date and the storage temperature 
in the space provided on the carton.  
Once you have taken the product out of the refrigerator for storage you must not store it again in the 
refrigerator.Do not freeze. Store in the original package in order to protect from light. 
 
After reconstitution (after the powder has been mixed with the solvent): 
Once you have reconstituted Esperoct, it should be used immediately. If you cannot use the 
reconstituted solution immediately, it should be used within  
• 24 hours when stored in a refrigerator (2°C - 8°C) or  
• 4 hours at ≤30°C or 
• 1 hour between >30°C and 40°C, only if the product was stored above room temperature 

(>30°C up to 40°C) before reconstitution for no longer than 3 months. 
 
The powder in the vial appears as a white to off-white powder. Do not use the powder if the colour has 
changed. 
 
The reconstituted solution must be clear and colourless. Do not use the reconstituted solution if you 
notice any particles or discolouration. 
 

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


45 

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 Esperoct contains 
• The active substance is turoctocog alfa pegol (pegylated human coagulation factor VIII 

(rDNA)). Each vial of Esperoct contains nominally 500, 1000, 1500, 2000 or 3000 IU 
turoctocog alfa pegol. 

• 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 9 mg/mL (0.9%) solution for injection 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 125, 250, 375, 500 or 750 IU 
turoctocog alfa pegol per mL, respectively (based on the strength of turoctocog alfa pegol, i.e. 500, 
1000, 1500, 2000 or 3000 IU). 
 
What Esperoct looks like and contents of the pack 
Esperoct is available in packs containing 500 IU, 1000 IU, 1500 IU, 2000 IU, or 3000 IU. Each pack 
of Esperoct contains a vial with white to off-white powder, a 4 mL pre-filled syringe with a clear 
colourless solvent, 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. 
  



46 

Instructions on how to use Esperoct 
 
Read these instructions carefully before using Esperoct. 
 
Esperoct is supplied as a powder. Before injection, it must be reconstituted with the solvent supplied 
in the syringe. The solvent is a sodium chloride 9 mg/mL (0.9%) solution for injection. The 
reconstituted product must be injected into your vein (intravenous (IV) injection). The equipment in 
this package is designed to reconstitute and inject Esperoct. 
 
You will also need: 
• an infusion set (butterfly needle with tubing) 
• sterile alcohol swabs 
• gauze pads and plasters. 
These items are not included in the Esperoct 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 a vein, it is important to use a clean and 
germ- free (aseptic) technique. An incorrect technique can introduce germs that can infect your 
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 has expired. Use a new package instead. The expiry date is printed 
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 Esperoct powder 
• 1 vial adapter 
• 1 pre-filled syringe with solvent 
• 1 plunger rod (placed under the syringe) 



47 

 
Overview 

Plastic cap 
Rubber stopper 

(under plastic cap) 

Vial with Esperoct powder 

 

 
Vial adapter 

Protective cap 

Spike 
(under protective paper) 

Protective 
paper 

 

 Pre-filled syringe with solvent 

Syringe tip 
(under syringe cap) Scale 

Plunger 

Syringe cap 
 

 Plunger rod 

Thread Wide top 
end 

 



48 

1. Prepare the vial and the syringe 
 
• Take out the number of Esperoct 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 let them 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, see figure A. 
 
Do not use any other way to warm the vial and 
pre-filled syringe. 

 A 

 

• 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 

 



49 

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

 F 

 

• 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 

 



50 

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 and colourless and no particles should be 
visible. If you notice particles or 
discolouration, do not use it. Use a new package 
instead. 

 J 

 

Esperoct is recommended to be used immediately after it has been reconstituted. 
 
If you cannot use the reconstituted Esperoct solution immediately, it should be used within: 
• 24 hours when stored in a refrigerator (2°C – 8°C) or 
• 4 hours (≤30°C) or 
• 1 hour between >30C and 40°C, only if the product was stored above room temperature 

(>30°C up to 40°C) before reconstitution for no longer than 3 months. 
 
Store the reconstituted product in the vial. 
 
Do not freeze the reconstituted solution or store it in syringes. 
 
Keep the reconstituted solution out of direct light. 
 

 
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. 

 K 

 



51 

 
• If you do not need to use all of the 

reconstituted medicine from the vial, 
use the scale on the syringe to withdraw 
the dose you need, as instructed by your 
doctor or nurse. 
 
If, at any point, there is 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. 

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

chloride 9 mg/mL (0.9%) solution for injection. 



52 

Disposal 
 

• After injection, safely dispose of all 
unused Esperoct 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. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER 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