Jivi

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 250 IU powder and solvent for solution for injection 
Jivi 500 IU powder and solvent for solution for injection 
Jivi 1000 IU powder and solvent for solution for injection 
Jivi 2000 IU powder and solvent for solution for injection 
Jivi 3000 IU powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Jivi 250 IU powder and solvent for solution for injection  
After reconstitution with the solvent provided, one mL of solution contains approximately 100 IU 
(250 IU/2.5 mL) of human coagulation factor VIII, damoctocog alfa pegol. 
 
Jivi 500 IU powder and solvent for solution for injection  
After reconstitution with the solvent provided, one mL of solution contains approximately 200 IU 
(500 IU/2.5 mL) of human coagulation factor VIII, damoctocog alfa pegol. 
 
Jivi 1000 IU powder and solvent for solution for injection  
After reconstitution with the solvent provided, one mL of solution contains approximately 400 IU 
(1000 IU/2.5 mL) of human coagulation factor VIII, damoctocog alfa pegol. 
 
Jivi 2000 IU powder and solvent for solution for injection  
After reconstitution with the solvent provided, one mL of solution contains approximately 800 IU 
(2000 IU/2.5 mL) of human coagulation factor VIII, damoctocog alfa pegol. 
 
Jivi 3000 IU powder and solvent for solution for injection  
After reconstitution with the solvent provided, one mL of solution contains approximately 1200 IU 
(3000 IU/2.5 mL) of human coagulation factor VIII, damoctocog alfa pegol. 
 
The potency International Unit (IU) is determined using the European Pharmacopoeia chromogenic 
assay. 
The specific activity of Jivi is approximately 10000 IU/mg protein. 
 
The active substance, damoctocog alfa pegol, is a site specifically PEGylated B-domain deleted 
recombinant human coagulation factor VIII, produced in baby hamster kidney cells (BHK), with a 
60 kDa branched polyethylene-glycol (two 30 kDa PEG) moiety. The molecular weight of the protein 
is approximately 234 kDa. 
 
Jivi is produced without the addition of any human or animal derived protein in the cell culture 
process, purification, PEGylation or final formulation.  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection. 
 



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Powder: solid, white to slightly yellow. 
Solvent: clear solution. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment and prophylaxis of bleeding in previously treated patients ≥ 12 years of age with 
haemophilia A (congenital factor VIII deficiency). 
 
4.2 Posology and method of administration 
 
Treatment should be under the supervision of a physician experienced in the treatment of haemophilia. 
 
Treatment monitoring 
 
During the course of treatment, appropriate determination of factor VIII levels is advised to confirm 
that adequate FVIII levels have been achieved. Individual patients may vary in their response to 
factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight may require 
adjustment in overweight patients. In the case of major surgical interventions in particular, precise 
monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is 
indispensable. 
 
When using an in vitro activated partial 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, 
which can result in over- or under-estimation of factor VIII activity. It should be noted that there can 
be significant discrepancies between assay results obtained by specific reagents used in the aPTT-
based one stage clotting assay and the chromogenic assay. This is of importance when monitoring the 
factor VIII activity of Jivi, and when changing laboratory and/or reagents used in the assay. This 
applies also for modified long acting factor VIII products. 
Laboratories intending to measure Jivi activity should check their procedures for accuracy. A field 
study has indicated that the factor VIII activity of Jivi can be accurately measured in plasma using 
either a validated chromogenic substrate (CS) assay or a one-stage (OS) clotting assay using specific 
reagents. For Jivi some silica-based one-stage assays (e.g., APTT-SP, STA-PTT) may underestimate 
the factor VIII activity of Jivi in plasma samples; some reagents, e.g. with kaolin-based activators, 
have the potential for overestimation. 
 
The clinical effect of factor VIII is the most important element in evaluating the effectiveness of 
treatment. It may be necessary to adjust the individual dosing at patient level in order to attain 
satisfactory clinical results. If the calculated dose fails to attain the expected factor VIII levels or if 
bleeding is not controlled after administration of the calculated dosage, the presence of a circulating 
factor VIII-inhibitor or anti-PEG antibodies in the patient should be suspected (see section 4.4). 
 
Posology 
 
The dose and duration of substitution therapy depends on the severity of the factor VIII deficiency, the 
location and extent of the bleeding and on the patient's clinical condition. 
The number of units of factor VIII administered is expressed in International Units (IU), which are 
related to the current WHO concentrate standard for factor VIII products. Factor VIII activity in 
plasma is expressed either as a percentage (relative to normal human plasma) or preferably in IU 
(relative to an International Standard for factor VIII in plasma). 
 
One IU of factor VIII activity is equivalent to that quantity of factor VIII in one mL of normal human 
plasma.  
 



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On demand treatment 
 
The calculation of the required dose of factor VIII is based on the empirical finding that 1 IU 
factor VIII per kg body weight raises the plasma factor VIII activity by 1.5-2.5 % of normal activity. 
The required dose of Jivi is determined using the following formula: 
 
Required units = body weight (kg) x desired factor VIII rise (% or IU/dL) x reciprocal of observed 
recovery (i.e. 0.5 for recovery of 2.0%). 
 
The amount to be administered and the frequency of administration should always be oriented to the 
clinical effectiveness required 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) 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 for adolescents and adults 
 

Degree of haemorrhage/Type 
of surgical procedure 

 

Factor VIII level 
required (%) 

(IU/dL) 

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

Haemorrhage 
 
Early haemarthrosis, muscle 
bleeding or oral bleeding 
 

20-40 

 
 
Repeat injection every 24-48 hours. 
At least 1 day, until bleeding episode as 
indicated by pain is resolved or healing is 
achieved 
 

More extensive 
haemarthrosis, muscle 
bleeding or haematoma 
 

30-60 
Repeat injection every 24-48 hours for 
3 to 4 days or more until pain and acute 
disability are resolved. 

Life-threatening  
 
Haemorrhages 
 

 
60-100 

 
 
Repeat injection 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 
post-operative) 

Repeat dose every  
12-24 hours until adequate wound healing, 
then therapy for at least another 7 days to 
maintain factor VIII activity of 30-60% 
(IU/dL). 

 
Prophylaxis 
 
All treatment decisions for identifying appropriate prophylactic treatment regimens should be guided 
by clinical judgement based on individual patient characteristics and treatment response. 
 
For prophylaxis the dose is 45-60 IU/kg every 5 days. Based on patient clinical characteristics the dose 
can also be 60 IU/kg every 7 days or 30-40 IU/kg two times per week (see sections 5.1 and 5.2). 
 



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For overweight patients, the maximum dose per injection for prophylaxis should not be higher than 
approximately 6000 IU.  
 
Paediatric population 
Jivi is not indicated in previously untreated patients and in patients less than 12 years of age. 
 
Adolescent population 
On demand and prophylactic treatment dosing in adolescent patients is the same as for adult patients. 
 
Elderly population 
There is limited experience in patients ≥ 65 years. 
 
Method of administration 
 
Jivi is for intravenous use. 
 
Jivi should be injected intravenously over a period of 2 to 5 minutes depending on the total volume. 
The rate of administration should be determined by the patient’s comfort level (maximal rate of 
injection: 2.5 mL/min). 
 
For instructions on reconstitution of the medicinal product before administration, see section 6.6 and 
the package leaflet. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
Known allergic reactions to mouse or hamster proteins. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Hypersensitivity 
 
Allergic type hypersensitivity reactions are possible with Jivi. The medicinal product may contain 
traces of mouse and hamster proteins. Hypersensitivity reactions could also be related to antibodies 
against PEG (see paragraph Immune response to polyethylene glycol (PEG)). If symptoms of 
hypersensitivity occur, patients should be advised to discontinue the use of the medicinal product 
immediately and contact their physician. Patients should be informed of the early signs of 
hypersensitivity reactions including hives, generalized urticaria, tightness of the chest, wheezing, 
hypotension, and anaphylaxis. Symptomatic treatment for hypersensitivity should be instituted as 
appropriate. In case of anaphylaxis or shock, the current medical standards for treatment should be 
implemented. 
 



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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 Bethesda 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 (ED) but continues throughout life although the risk is uncommon. Rarely, inhibitors 
may develop after the first 50 exposure days. 
 
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. 
 
Immune response to polyethylene glycol (PEG) 
 
A clinical immune response associated with anti-PEG antibodies, manifested as symptoms of acute 
hypersensitivity and/or loss of drug effect has been observed primarily within the first 4 exposure 
days. Low post-injection factor VIII levels in the absence of detectable factor VIII inhibitors indicate 
that loss of drug effect is likely due to anti-PEG antibodies; in such cases Jivi should be discontinued 
and patients switched to a previously effective factor VIII product. 
 
A significant decrease in the risk of an immune response to PEG was observed with an increase in age. 
This effect may be related to a developmental change in immunity, and although it is difficult to define 
a clear cut-off age for the change in risk, this phenomenon predominantly occurs in young children 
with haemophilia. 
 
The implications of any potential risk to affected patients with a hypersensitivity reaction to pegylated 
proteins are unknown. Data show that in the affected subjects, following discontinuation of Jivi, the 
anti-PEG IgM antibodies decreased in titre and became undetectable over time . No cross-reactivity of 
anti-PEG IgM antibodies with other unmodified factor VIII products was observed. All patients could 
be successfully treated with their previous factor VIII products. 
 
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, 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. 
Jivi is not indicated in patients < 12 years of age and in previously untreated patients. 
 



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Sodium content 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 
‘sodium-free’. 
 
4.5 Interactions with other medicinal products and other forms of interaction 
 
Interactions of human coagulation factor VIII (rDNA) products with other medicinal products have 
not been reported. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy and breast-feeding 
 
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 breast-feeding 
only if clearly indicated. 
 
Fertility 
 
In the repeat dose systemic toxicity studies in rats and rabbits with Jivi, treatment related effects on 
male reproductive organs were not seen (see section 5.3). The effect on fertility in humans is 
unknown. 
 
4.7 Effects on ability to drive and use machines 
 
Jivi 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 
injection site, chills, flushing, generalized urticaria, headache, hives, hypotension, lethargy, nausea, 
restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed and 
may in some cases progress to severe anaphylaxis (including shock). 
 
Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated 
with factor VIII, including with Jivi (see section 5.1). If such inhibitors occur, the condition will 
manifest itself as an insufficient clinical response. In such cases, it is recommended that a specialized 
haemophilia centre be contacted. 
 
The most frequently reported adverse reactions in clinical trials in PTPs were headache, cough and 
pyrexia. 
 
Tabulated list of adverse reactions 
 
A total of 221 patients constituted the safety population from three pivotal Phase I and III studies 
[PROTECT VIII]. Median time on study for the 148 patients ≥12 years of age was 713 days. The total 
number of exposure days (ED) was 18432 with a median of 131 ED (range: 1 to 309) per subject; 
median time in study for paediatric patients < 12 years was 237 days with a total of 3219 ED and 
median of 53 ED (range 1-68) per subject. 
 



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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). 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
Table 2: Frequency of adverse drug reactions in clinical trials 
 
MedDRA Standard  
System Organ Class  

Adverse reactions  Frequency  
 

Blood and lymphatic system disorders FVIII inhibition Uncommon (PTPs)* 
 

Immune system disorders Hypersensitivity common 
Psychiatric disorders Insomnia common 
Nervous system disorders Headache very common 

Dizziness common 
Dysgeusia  uncommon 

Vascular disorders Flushing uncommon 
Respiratory, thoracic and mediastinal 
disorders 

Cough common 

Gastrointestinal disorders Abdominal pain, Nausea, 
Vomiting 

common 

Skin and subcutaneous tissue disorders Erythema***, Rash**** common 
Pruritus uncommon 

General disorders and administration 
site conditions 

Injection site reactions **, 
Pyrexia 

common 

* Frequency is based on studies with all factor VIII products which included patients with severe 
haemophilia A. PTPs = previously-treated patients” 

**includes injection site pruritus, injection site rash and vessel puncture site pruritus 
***includes erythema and erythema multiforme  
****includes rash and rash papular 
 
Description of selected adverse reactions 
 
Immunogenicity 
Immunogenicity was evaluated during clinical trials with Jivi in 159 (including surgery patients) 
previously treated adolescents (≥ 12 years of age) and adults diagnosed with severe haemophilia A 
(FVIII:C < 1%), and ≥ 150 previous exposure days. Median time on study was 713 days with a 
median of 131 exposure days (range: 1 to 309 days). 
 
FVIII inhibitors 
No de novo or confirmed cases of inhibitor against factor VIII occurred. A single unconfirmed positive 
result of a low titre of factor VIII inhibitor (1.7 BU/mL) was reported in one adult patient following a 
surgery. 
 
Anti¬PEG antibodies 
Immunogenicity against PEG with development of specific IgM anti-PEG antibodies was observed in 
one patient. The immune response was accompanied by a clinical hypersensitivity reaction after 
4 injections of Jivi. Antibodies to PEG disappeared after discontinuation of Jivi. 
 
Paediatric population 
In completed clinical studies with 73 paediatric PTPs < 12 years (44 PTPs < 6 years, 29 PTPs 
6¬<12 years), adverse reactions due to immune response to PEG were observed in children less than 



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6 years of age. In 10 of 44  patients (23%) in the age group of younger than 6 years of age loss of drug 
effect due to neutralising anti-PEG antibodies during the first 4 exposure days was observed. In 
3 of 44  patients (7%), loss of drug effect was combined with hypersensitivity reactions (see 
section 4.4). No triggers or predictors of the immune response to PEG could be identified. 
 
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 
 
There was one case of overdose in the clinical trials. No adverse events were reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: antihaemorrhagics: blood coagulation factor VIII, ATC code: B02BD02. 
 
Mechanism of action 
 
The factor VIII/von Willebrand factor complex consists of two molecules (factor VIII and von 
Willebrand factor) with different physiological functions. When infused into a patient with 
haemophilia, factor VIII binds to patient’s von Willebrand factor. 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 or absence of factor VIII:C that results in 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 the bleeding tendencies. 
 
Damoctocog alfa pegol is a PEGylated form of rFVIII. Site-specific PEGylation reduces clearance of 
factor VIII resulting in an extended half-life while maintaining the normal functions of the B-domain 
deleted rFVIII molecule (see section 5.2). Damoctocog alfa pegol does not contain von Willebrand 
factor. 
 
Clinical efficacy and safety 
 
Clinical studies 
 
A total of 232 previously treated patients with severe haemophilia A have been exposed in the clinical 
trial program which included one phase I study and two phase II/III studies. One-hundred and fifty 
nine (159) subjects were ≥ 12 years of age,  
 
Phase II/III: The pharmacokinetics, safety and efficacy of Jivi for on demand treatment, prophylaxis 

with three regimens (two times per week 30-40 IU/kg, every 5-days 45-60 IU/kg and every 
7-days 60 IU/kg) and haemostasis during major surgeries were evaluated in a multi-
national, open-label, uncontrolled, partially randomized study which was performed in 
compliance with the agreed Paediatric Investigation Plan. An extension study included 
patients completing the main study. The primary efficacy variable was annualized bleed 
rate (ABR). 

 



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One hundred and thirty four male PTPs received at least one injection of Jivi (including 
13 subjects aged 12 to 17 years of age) for prophylaxis (n=114) or on-demand treatment 
(n=20) for a period of 36 weeks. A total of 121 subjects received treatment during the 
extension study with a median duration of 464 days. Hemostasis during 20 major surgeries 
in 17 patients was evaluated in the surgery part. 

 
Phase III (Paediatric): Pharmacokinetics, safety, and efficacy of Jivi for three prophylaxis regimens 

(twice weekly, every 5 and every 7 days) and treatment of breakthrough bleeds were 
evaluated in a multi-national, uncontrolled, open-label trial in 73 paediatric patients 
(<12 years of age) during a period of 50 EDs and at least 6 months. This study has been 
performed in compliance with the agreed Paediatric Investigation Plan. Sixty one subjects 
(83.6%) completed the main study and 59 patients continued in the optional extension 
study.  

 
Prophylactic treatment in subjects ≥12 years 
 
During the main study period subjects were assigned to prophylaxis 2x/week (n=24), or randomized to 
every 5 days (n=43) or every 7 days (n=43) or received on-demand treatment (n=20) with Jivi. Ninety 
nine of 110 patients (90%) remained on the assigned regimen. Eleven patients in the every 7 days arm 
increased frequency. The median dose for all prophylaxis regimens was 46.9 IU/kg/injection. The 
median (Q1; Q3) ABR during prophylaxis was 2.09 (0.0; 6.1) for all bleeds and 0.0 (0;0 4.2) for 
spontaneous bleeds as compared to 23.4 (18; 37) total bleeds in the on-demand group. Forty-two out 
of 110 in the prophylaxis arms (38.2%) experienced no bleeding episode.  
 
During the extension study, 24 patients were treated 2x/week, 37 patients every 5-days, 29 patients 
every 7 days and 17 patients changed treatment regimen. The median dose for prophylaxis was 
47.7 IU/kg. The overall median (Q1; Q3) total ABR was 1.17 (0.0; 4.3) and 0.6 (0.0: 3.2) for 
spontaneous bleeds in the combined prophylaxis groups and total ABR was 33.0 in the on-demand 
group. 
Of note, ABR is not comparable between different factor concentrates and between different clinical 
studies. 
 
Treatment of bleeding 
 
Of the 702 bleeding events treated with Jivi during the main study, 636 (90.6%) were treated with 1 or 
2 injections, thereof 81.1% with 1 injection. The median (range) dose per injection was 31.7 IU/kg 
(14; 62). During the extension, 942 bleeds were treated with Jivi and 92.3% were controlled with 1 or 
2 injections, thereof 83% with 1 injection. The median (range) dose was 37.3 (18; 66) IU/kg/injection. 
 
Perioperative Management  
 
A total of 20 major surgical procedures were performed and assessed in 17 patients. The median total 
dose for major surgeries was 219 IU/kg (range: 50-1500 IU/kg, including postoperative period up to 
3 weeks). Perioperative haemostatic efficacy was rated as good or excellent during all major surgeries. 
Additional 34 minor surgeries were performed in 19 patients. Hemostasis was assessed as good or 
excellent in all available cases. 
 
Paediatric population < 12 years of age 
 
The use of Jivi in children below 12 years is not indicated (see section 4.2, for information on 
paediatric use).  
A total of 73  previously treated pediatric patients (44 subjects < 6 years and 29 subjects 
6 to <12 years) received prophylaxis treatment twice weekly, every 5 days or every 7 days in the phase 
III study. For 53 patients who completed the main study, the median (Q1; Q3) annualised bleeding rate 
was 2.87 (1.1; 6.1) and the spontaneous ABR was 0.0 (0.0; 2.6). For treatment of bleeds, 84.4 % of the 
bleeds were resolved with 1 injection, and 91.9% of the bleeds were resolved with 1 or 2 injections. 



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11 patients in the age group < 6 years dropped out due to an immune response to PEG associated with 
loss of efficacy and/or hypersensitivity reaction during the first four ED. 
 
5.2 Pharmacokinetic properties 
 
The pharmacokinetics (PK) of Jivi was compared to that of factor VIII in a crossover Phase I study. 
PK was also evaluated in 22 subjects (≥12 yrs) and in 16 of these subjects after 6 months of 
prophylaxis treatment in the Phase II/III study. 
 
The PK data (based on chromogenic assay) indicated that Jivi has a reduced clearance (CL), resulting 
in a terminal half-life that is 1.4-fold longer and a dose normalized AUC which is 1.4-fold higher, as 
compared to the comparative factor VIII product. Dose proportional increases were observed between 
the doses of 25 and 60 IU/kg indicating dose linearity between 25 IU/kg and 60 IU/kg. 
 
Table 3 summarizes the PK parameters after single dose of 60 IU/kg from the Phase II/III study where 
PK was evaluated in 22 subjects. Repeated PK measurements did not indicate any relevant changes in 
PK characteristics after long-term treatment.  
 
Table 3: Pharmacokinetic parameters (geometric mean (%CV) and arithmetic mean (SD)) for 
Jivi following a single 60 IU/kg dose based on chromogenic assay. 
 

Parameters (units)  Jivi 
Patients ≥12 years 

n=22 
AUC (IU*h/dL) 3710 (33.8) 

3900 ± 1280 
AUC, norm (h*kg/dL) 62.5 (33.7) 

65.7 ± 21.4 
Cmax (IU/dL) 163 (14.7) 

164 ± 23.8 
t½ (h) 17.1 (27.1) 

17.6 ± 4.26 
MRTIV (h) 24.4 (27.5) 

25.2 ± 6.19 
Vss (dL/kg) 0.391 (16.3) 

0.396 ± 0.0631 
CL (dL/h/kg) 0.0160 (33.7) 

0.0168 ± 0.00553 
AUC: area under the curve; AUC, norm: dose normalized AUC Cmax: maximum drug concentration; ,  
t½: terminal half¬life; MRT IV : mean residence time after an intravenous administration; VSS: apparent volume 
distribution at steady¬state; CL: clearance 

 
Incremental recovery was determined in 131 patients at several time points. The median (Q1; Q3) 
recovery was 2.6 (2.3; 3.0) by chromogenic assay. 
 
A population PK model was developed based on all available factor VIII measurements (from dense 
PK sampling and all recovery samples) throughout the 3 clinical studies allowing calculation of PK 
parameters for subjects in the various studies. The table 4 below provides PK parameters based on the 
population PK model. 
 



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Table 4: PK parameters (geometric mean [%CV]) based on population PK model, using 
chromogenic assay. 
 

PK parameter(unit) 12-<18 years 
N=12 

≥ 18 years 
N=133 

Total (≥ 12 years)  
N=145 

AUC (IU.h/dL)* 3341 (34.2) 4052 (31.1) 3997 (31.6) 

AUCnorm (kg.h/dL) 57.4 (32.6) 67.5 (30.6) 66.6 (31.0) 
t1/2 (h) 16.8 (25.2) 17.4 (28.8) 17.4 (28.4) 

Vss (dL/kg) 0.423 (15.5) 0.373 (15.6) 0.376 (15.9) 
CL (dL/h/kg) 0.0174 (34.2) 0.0148 (31.1) 0.0150 (31.6) 

*AUC calculated for a dose of 60 IU/kg 
 
5.3 Preclinical safety data 
 
Jivi was evaluated in pharmacology, single and repeated dose as well as juvenile toxicity studies in 
rats and rabbits. In a long-term, 6-months chronic toxicity study no indication of PEG accumulation or 
other effects related to administration of Jivi were seen. In addition 4 weeks toxicity studies with the 
PEG moiety of Jivi were conducted in two species. The PEG-linker moiety was also tested in a 
standard set of in vivo and in vitro genotoxicity studies and they did not indicate a potential for 
genotoxicity. These studies did not reveal any safety concerns for humans.  
 
Single dose studies in rats with the radio-labelled PEG moiety showed that there was no indication of 
retention or irreversible binding of radioactivity in the animal body. Specifically, no residual 
radioactivity was detected in the brain, indicating that the radio-labelled compound did not cross the 
blood brain barrier. In distribution and excretion studies in rats, the 60 kDa PEG moiety of Jivi was 
shown to be widely distributed to and eliminated from organs and tissues, and excreted in urine 
(68.4% up to day 231 after administration) and faeces (13.8% up to day 168 after administration). 
 
No long-term studies in animals to evaluate the carcinogenic potential of Jivi, or studies to determine 
the effects of Jivi on reproduction have been conducted. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder 
Sucrose 
Histidine 
Glycine 
Sodium chloride 
Calcium chloride dihydrate 
Polysorbate 80 
Acetic acid, glacial (for pH adjustment) 
 
Solvent 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 



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Only the components provided in the package should be used for reconstitution and injection because 
treatment failure can occur as a consequence of factor VIII adsorption to the internal surfaces of some 
injection equipment. 
 
6.3 Shelf¬life 
 
Unopened vial 
 
2 years. 
 
Reconstituted solution 
 
The chemical and physical in-use stability after reconstitution has been demonstrated for 3 hours at 
room temperature. Do not refrigerate after reconstitution. 
From a microbiological point of view the product should be used immediately after reconstitution. If 
not used immediately, the in-use storage times and conditions prior to use are the responsibility of the 
user. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2 °C ¬ 8 °C). 
Do not freeze.  
Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
Within its overall shelf life of 2 years, the product (when kept in its outer carton) may be stored at up 
to 25 °C for a limited period of 6 months. The end date of the 6 month storage period at a temperature 
up to 25 °C should be recorded on the product carton. This date should never exceed the expiry date 
printed on the outer carton. At the end of this period the product should not be put back in the 
refrigerator, but should be used or discarded. 
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
Each single package of Jivi contains: 
• one vial with powder (10 mL clear type 1 glass vial with grey bromobutyl rubber blend stopper 

and aluminium seal) 
• one pre-filled syringe with 2.5 mL solvent (clear type 1 glass cylinder syringe with grey 

bromobutyl rubber blend stopper) 
• one syringe plunger rod 
• one vial adapter (with integrated filter) 
• one venipuncture set 
 
Pack sizes 
 1 single pack. 
 1 multipack with 30 single packs. 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
Detailed instructions for preparation and administration are contained in the package leaflet provided 
with Jivi. 
 
Jivi powder should only be reconstituted with the supplied solvent (2.5 mL water for injections) in the 
prefilled-syringe and the vial adapter. The medicinal product must be prepared for injection under 
aseptic conditions. If any component of the package is opened or damaged, do not use this component. 



14 

After reconstitution the solution is clear and colourless and then drawn back into the syringe. 
Parenteral medicinal products should be inspected visually for particulate matter and discolouration 
prior to administration 
 
The reconstituted product must be filtered prior to administration to remove potential particulate 
matter in the solution. Filtering is achieved by using the vial adapter. 
 
Jivi is for single use only. 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBERS 
 
EU/1/18/1324/001 – 1 x (Jivi 250 IU) 
EU/1/18/1324/002 – 1 x (Jivi 500 IU) 
EU/1/18/1324/003 – 1 x (Jivi 1000 IU) 
EU/1/18/1324/004 – 1 x (Jivi 2000 IU) 
EU/1/18/1324/005 – 1 x (Jivi 3000 IU) 
EU/1/18/1324/006 – 30 x (Jivi 250 IU) 
EU/1/18/1324/007 – 30 x (Jivi 500 IU) 
EU/1/18/1324/008 – 30 x (Jivi 1000 IU) 
EU/1/18/1324/009 – 30 x (Jivi 2000 IU) 
EU/1/18/1324/010 – 30 x (Jivi 3000 IU) 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 22 November 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. 
 



15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 
 



16 

 

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

Name and address of the manufacturer of the biological active substance  

Bayer HealthCare LLC 
800 Dwight Way 
Berkeley 
CA 
94710 
United States 
 
Name and address of the manufacturer responsible for batch release 

Bayer AG 
Kaiser-Wilhelm-Allee 
51368 Leverkusen 
Germany 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 

 

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 (MAH) shall submit the first PSUR 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 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; 



17 

 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 
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 non-
interventional post-authorisation safety study according to an agreed protocol. 
 

Final study protocol 
should be submitted 
within 3 months 
after CHMP 
Opinion.  
 
Final study report 
should be submitted 
by 31 December 
2028  

 
 



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



20 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON OF A SINGLE PACK (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 250 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 250 IU contains 100 IU damoctocog alfa pegol per mL after reconstitution (250 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
For reconstitution using the vial adapter read package leaflet before use. 
 

 
 
 



21 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 
May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/001 – 1 x (Jivi 250 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



22 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 250 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 



23 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER LABEL OF MULTIPACK WITH 30 SINGLE PACKS (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 250 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 250 IU contains 100 IU damoctocog alfa pegol per mL after reconstitution (250 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
Multipack with 30 single packs, each containing: 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 



24 

May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/006 – 30 x (Jivi 250 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 250 
 
 



25 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



26 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INNER CARTON OF A MULTIPACK (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 250 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 250 IU contains 100 IU damoctocog alfa pegol per mL after reconstitution (250 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
Component of a multipack, can’t be sold separately. 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
For reconstitution using the vial adapter read package leaflet before use. 
 

 
 
 



27 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 
May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/006 – 30 x (Jivi 250 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



28 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 250 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 



29 

 
 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Jivi 250 IU powder for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
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 (damoctocog alfa pegol) . 
 
 
6. OTHER 
 
Bayer-Logo 
 



30 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON OF A SINGLE PACK (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 500 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 500 IU contains 200 IU damoctocog alfa pegol per mL after reconstitution (500 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
For reconstitution using the vial adapter read package leaflet before use. 
 

 
 
 



31 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 
May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/002 – 1 x (Jivi 500 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



32 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 500 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 



33 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER LABEL OF MULTIPACK WITH 30 SINGLE PACKS (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 500 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 500 IU contains 200 IU damoctocog alfa pegol per mL after reconstitution (500 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
Multipack with 30 single packs, each containing: 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 



34 

May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/007 – 30 x (Jivi 500 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 500 
 
 



35 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



36 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INNER CARTON OF A MULTIPACK (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 500 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 500 IU contains 200 IU damoctocog alfa pegol per mL after reconstitution (500 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
Component of a multipack, can’t be sold separately. 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
For reconstitution using the vial adapter read package leaflet before use. 
 

 
 
 



37 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 
May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/007 – 30 x (Jivi 500 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



38 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 500 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 



39 

 
 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Jivi 500 IU powder for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
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 (damoctocog alfa pegol). 
 
 
6. OTHER 
 
Bayer-Logo 
 



40 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON OF A SINGLE PACK (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 1000 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 1000 IU contains 400 IU damoctocog alfa pegol per mL after reconstitution (1000 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
For reconstitution using the vial adapter read package leaflet before use. 
 

 
 
 



41 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 
May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/003 – 1 x (Jivi 1000 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



42 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 1000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 



43 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER LABEL OF MULTIPACK WITH 30 SINGLE PACKS (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 1000 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 1000 IU contains 400 IU damoctocog alfa pegol per mL after reconstitution (1000 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
Multipack with 30 single packs, each containing: 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 



44 

May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/008 – 30 x (Jivi 1000 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 1000 
 
 



45 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



46 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INNER CARTON OF A MULTIPACK (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 1000 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 1000 IU contains 400 IU damoctocog alfa pegol per mL after reconstitution (1000 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
Component of a multipack, can’t be sold separately. 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
For reconstitution using the vial adapter read package leaflet before use. 
 

 
 
 



47 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 
May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/008 – 30 x (Jivi 1000 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



48 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 1000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 



49 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Jivi 1000 IU powder for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
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 (damoctocog alfa pegol). 
 
 
6. OTHER 
 
Bayer-Logo 
 



50 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON OF A SINGLE PACK (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 2000 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 2000 IU contains 800 IU damoctocog alfa pegol per mL after reconstitution (2000 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
For reconstitution using the vial adapter read package leaflet before use. 
 

 
 
 



51 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 
May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/004 -1 x ( Jivi 2000 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



52 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 2000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 



53 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER LABEL OF MULTIPACK WITH 30 SINGLE PACKS (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 2000 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 2000 IU contains 800 IU damoctocog alfa pegol per mL after reconstitution (2000 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
Multipack with 30 single packs, each containing: 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 



54 

May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/009 – 30 x (Jivi 2000 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 2000 
 
 



55 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



56 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INNER CARTON OF A MULTIPACK (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 2000 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 2000 IU contains 800 IU damoctocog alfa pegol per mL after reconstitution (2000 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
Component of a multipack, can’t be sold separately. 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
For reconstitution using the vial adapter read package leaflet before use. 
 

 
 
 



57 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 
May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/009 – 30 x (Jivi 2000 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



58 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 2000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 



59 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Jivi 2000 IU powder for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
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 (damoctocog alfa pegol). 
 
 
6. OTHER 
 
Bayer-Logo 
 



60 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON OF A SINGLE PACK (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 3000 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 3000 IU contains 1200 IU damoctocog alfa pegol per mL after reconstitution (3000 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
For reconstitution using the vial adapter read package leaflet before use. 
 

 
 
 



61 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 
May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/005 – 1 x (Jivi 3000 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



62 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 3000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 
 



63 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER LABEL OF MULTIPACK WITH 30 SINGLE PACKS (INCLUDING BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 3000 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 3000 IU contains 1200 IU damoctocog alfa pegol per mL after reconstitution (3000 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
Multipack with 30 single packs, each containing: 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 



64 

May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/010 – 30 x (Jivi 3000 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 3000 
 
 



65 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 
 



66 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
INNER CARTON OF A MULTIPACK (WITHOUT BLUE BOX) 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Jivi 3000 IU powder and solvent for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Jivi 3000 IU contains 1200 IU damoctocog alfa pegol per mL after reconstitution (3000 IU / 2.5 mL). 
 
 
3. LIST OF EXCIPIENTS 
 
Sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, polysorbate 80, acetic acid 
glacial and water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection. 
 
Component of a multipack, can’t be sold separately. 
 
1 vial with powder, 1 pre-filled syringe with 2.5 mL water for injections, 1 vial adapter and 
1 venipuncture set. 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. Single dose only. 
Read the package leaflet before use. 
 
For reconstitution using the vial adapter read package leaflet before use. 
 

 
 
 



67 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 

 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
EXP (End of the 6 month period, if stored up to 25 °C): ................ 
Do not use after this date. 
 
May be stored at temperatures up to 25 °C for up to 6 months within the expiry date indicated on the 
label. Note the new expiry date on the carton. 
 
After reconstitution:  
 The product must be used within 3 hours. 
 Do not refrigerate after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Before reconstitution: 
 Store in a refrigerator. 
 Do not freeze. 
 Keep the vial and the pre-filled syringe in the outer carton in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
Any unused solution must be discarded. 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Bayer AG 
51368 Leverkusen 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/18/1324/010 – 30 x (Jivi 3000 IU) 
 
 
13. BATCH NUMBER 
 
Lot 
 
 



68 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
 
16. INFORMATION IN BRAILLE 
 
Jivi 3000 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
 



69 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
POWDER VIAL  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Jivi 3000 IU powder for solution for injection 
 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa 
pegol) 
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 (damoctocog alfa pegol). 
 
 
6. OTHER 
 
Bayer-Logo 
 



70 

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

ADMINISTRATION 
 
Water for injections 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
2.5 mL 
 
 
6. OTHER 
 
 
 



71 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 



72 

Package Leaflet: Information for the user 
 

Jivi 250 IU powder and solvent for solution for injection 
Jivi 500 IU powder and solvent for solution for injection 

Jivi 1000 IU powder and solvent for solution for injection 
Jivi 2000 IU powder and solvent for solution for injection 
Jivi 3000 IU powder and solvent for solution for injection 

 
PEGylated B-domain deleted recombinant human coagulation factor VIII (damoctocog alfa pegol) 
 
 

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

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
1. What Jivi is and what it is used for 
2. What you need to know before you use Jivi 
3. How to use Jivi  
4. Possible side effects 
5. How to store Jivi  
6. Contents of the pack and other information 
 
 
1. What Jivi is and what it is used for 
 
Jivi contains the active substance damoctocog alfa pegol. It is produced by recombinant technology 
without addition of any human- or animal-derived components in the manufacturing process. 
Factor VIII is a protein naturally found in the blood that helps to clot it. The protein in damoctocog 
alfa pegol has been modified (pegylated) to prolong its action in the body. 
 
Jivi is used to treat and prevent bleeding in previously treated adults and adolescents aged from 
12 years with haemophilia A (hereditary factor VIII deficiency). It is not for use in children younger 
than 12 years of age. 
 
 
2. What you need to know before you use Jivi 
 
Do not use Jivi if you are 
 allergic to damoctocog alfa pegol or any of the other ingredients of this medicine (listed in 

section 6). 
 allergic to mouse or hamster proteins. 
 
Warnings and precautions 
Talk to your doctor or pharmacist if you have 
 tightness in the chest, fall in blood pressure (often shown by feeling dizzy when getting up 

quickly), itchy nettle-rash, wheezing, feeling sick or faint. These may be signs of a rare severe 



73 

sudden allergic reaction to this medicine. Stop injecting the product immediately and get 
medical help at once if this occurs. 

 bleeding that is not being controlled with your usual dose of this medicine. Speak with your 
doctor immediately if this occurs. You may have developed antibodies against factor VIII 
(inhibitors) or antibodies against polyethylene glycol (PEG). These make Jivi less effective at 
preventing and controlling bleeding. Your doctor may carry out tests to confirm this and ensure 
that your Jivi dose provides adequate factor VIII levels. Your doctor may switch you back to 
your previous factor VIII treatment, if needed. 

 previously developed factor VIII inhibitors to a different product. 
 heart disease or you are at risk of heart disease.  
 to use a central venous access device for this medicine. You may be at risk of device-related 

complications where the catheter is inserted including: 
 local infections  
 bacteria in the blood 
 a blood clot in the blood vessel 

 
Children 
Jivi is not for use in children younger than 12 years of age. 
 
Other medicines and Jivi 
Jivi is not known to influence or be influenced by other medicines. Tell your doctor or pharmacist if 
you are using, have recently used or might use any other medicines. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before using this medicine. 
 
Driving and using machines 
Jivi has no influence on your ability to drive and use machines. 
 
Jivi contains sodium 
This medicine contains less than 1 mmol (23 mg) sodium per dose, and is therefore considered to be 
essentially ‘sodium-free’. 
 
 
3. How to use Jivi 
 
Treatment with Jivi will be started by a doctor who is experienced in the care of patients with 
haemophilia A. After suitable training patients or carers may be able to give Jivi at home. 
Always use this medicine exactly as described in this leaflet and as your doctor or pharmacist has told 
you. Check with your doctor or pharmacist if you are not sure. The dose of factor VIII units is 
measured in International Units (IU). 
 
Treatment of bleeding 
To treat a bleed, your doctor will calculate and adjust your dose and how often it should be given, 
depending on factors such as: 
 your weight 
 the severity of your haemophilia A 
 where the bleeding is and how serious it is 
 whether you have inhibitors and how high their level is 
 the factor VIII level that is needed. 
 



74 

Prevention of bleeding 
To prevent bleeding your doctor will select an appropriate dose and frequency depending on your 
need: 
 45–60 IU per kg body weight every 5 days or 
 60 IU per kg body weight every 7 days or 
 30-40 IU per kg body weight two times per week. 
 
Laboratory tests 
Laboratory tests at suitable intervals help to ensure you always have adequate factor VIII levels. For 
major surgery in particular, your blood clotting must be closely monitored. 
 
Duration of treatment 
Usually Jivi treatment for haemophilia is needed lifelong. 
 
How Jivi is given 
Jivi is injected into a vein over 2 to 5 minutes depending on the total volume and your comfort level. 
The maximum rate is 2.5 mL per minute. Jivi should be used within 3 hours after reconstitution. 
 
How Jivi is prepared for injection 
Use only the components (vial adapter, pre-filled syringe containing solvent and venipuncture set) 
provided with each package of this medicine. Please contact your doctor if these components cannot 
be used. Do not use if any component of the package is opened or damaged. 
 
The reconstituted product must be filtered by using the vial adapter before injection to remove any 
possible particles in the solution.  
 
This medicine must not be mixed with other injections. Do not use solutions that are cloudy or contain 
visible particles. Follow the instructions for use given by your doctor and provided at the end of this 
leaflet. 
 
If you use more Jivi than you should 
Tell your doctor if this occurs. No symptoms of overdose have been reported. 
 
If you forget to use Jivi 
Inject your next dose immediately and continue at regular intervals as advised by your doctor.  
Do not use a double dose to make up for a forgotten dose. 
 
If you stop using Jivi 
Do not stop using this medicine without checking with your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor or pharmacist. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The most serious side effects are allergic reactions or severe allergic reaction. Stop injecting Jivi 
immediately and speak to your doctor at once if such reactions occur. The following symptoms 
could be an early warning of these reactions: 
 chest tightness/general feeling of being unwell 
 burning and stinging at the application site 
 nettle¬rash, flushing 
 a reduction in blood pressure, which may make you feel faint upon standing 
 feeling sick (nausea) 
 



75 

For patients who have received previous treatment with factor VIII (more than 150 days of treatment) 
inhibitor antibodies (see section 2) may form uncommonly (less than 1 in 100 patients). If this happens 
your medicine may stop working properly and you may experience persistent bleeding. If this 
happens, you should contact your doctor immediately. 
 
The following side effects may occur with this medicine: 
 
Very common (may affect more than 1 in 10 people): 
 headache 
 
Common (may affect up to 1 in 10 people): 
 stomach pain  
 nausea, vomiting 
 fever 
 allergic reactions (may present as hives, generalized urticaria, tightness of the chest, wheezing, 

shortness of breath, low blood pressure, for early symptoms see above) 
 local reactions at the injection site such as bleeding under the skin, intense itching, swelling, 

burning sensation, temporary redness 
 dizziness 
 trouble falling asleep 
 cough 
 rash, skin reddening 
 
Uncommon (may affect up to 1 in 100 people): 
 taste disturbance 
 flushing 
 itching 
 
Reporting of side effects 

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 
leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 
By reporting side effects, you can help provide more information on the safety of this medicine. 
 
 
5. How to store Jivi  
 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on labels and cartons. The expiry date 
refers to the last day of that month. 
 
Store in a refrigerator (2 °C - 8 °C). Do not freeze. 
Keep the medicine in its original package in order to protect from light. 
 
This medicine may be stored at room temperature (up to 25 °C) for up to 6 months when you keep it in 
its outer carton. If you store it at room temperature it expires after 6 months, or the expiry date if this 
is earlier. 
The new expiry date must be noted on the outer carton when the medicine is removed from the 
refrigerator. 
 
Do not refrigerate the solution after reconstitution. The reconstituted solution must be used within 
3 hours. 
 
Do not use this medicine if you notice any particles or the solution is cloudy. 
 
This medicine is for single use only. Any unused solution must be discarded. 



76 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist or 
physician 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 Jivi contains 
 
The active substance is PEGylated B-domain deleted recombinant human coagulation factor VIII 
(damoctocog alfa pegol). Each vial of Jivi contains nominally 250 or 500 or 1000 or 2000 or 3000 IU 
damoctocog alfa pegol. 
The other ingredients are sucrose, histidine, glycine, sodium chloride, calcium chloride dihydrate, 
polysorbate 80, acetic acid glacial and water for injections. 
 
What Jivi looks like and contents of the pack 
 
Jivi is provided as a powder and solvent for solution for injection. The powder is dry, and white to 
slightly yellow. The solvent is a clear liquid. After reconstitution the solution is clear. 
 
Each single pack of Jivi contains 
 a glass vial of powder 
 a pre-filled syringe of solvent 
 a separate plunger rod 
 a vial adapter 
 a venipuncture set 
 
Jivi is available in pack sizes of: 
 1 single pack 
 1 multipack with 30 single packs 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder 
Bayer AG 
51368 Leverkusen 
Germany 
 
Manufacturer 
Bayer AG 
Kaiser-Wilhelm-Allee 
51368 Leverkusen 
Germany 
 
 



77 

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Bayer SA-NV 
Tél/Tel: +32-(0)2-535 63 11 

Lietuva 
UAB Bayer 
Tel. +37 05 23 36 868 

България 
Байер България ЕООД 
Tел.: +359 02 4247280 

Luxembourg/Luxemburg 
Bayer SA-NV 
Tél/Tel: +32-(0)2-535 63 11 

Česká republika 
Bayer s.r.o. 
Tel: +420 266 101 111 

Magyarország 
Bayer Hungária KFT 
Tel:+36 14 87-41 00 

Danmark 
Bayer A/S 
Tlf: +45 45 23 50 00 

Malta 
Alfred Gera and Sons Ltd. 
Tel: +35 621 44 62 05 

Deutschland 
Bayer Vital GmbH 
Tel: +49 (0)214-30 513 48 

Nederland 
Bayer B.V. 
Tel: +31-(0)297-28 06 66 

Eesti 
Bayer OÜ 
Tel: +372 655 8565 

Norge 
Bayer AS 
Tlf: +47 23 13 05 00 

Ελλάδα 
Bayer Ελλάς ΑΒΕΕ 
Τηλ: +30-210-61 87 500 

Österreich 
Bayer Austria Ges.m.b.H. 
Tel: +43-(0)1-711 46-0 

España 
Bayer Hispania S.L. 
Tel: +34-93-495 65 00 

Polska 
Bayer Sp. z o.o. 
Tel: +48 22 572 35 00 

France 
Bayer HealthCare 
Tél (N° vert): +33-(0)800 87 54 54 

Portugal 
Bayer Portugal, Lda. 
Tel: +351 21 416 42 00 

Hrvatska 
Bayer d.o.o. 
Tel: +385-(0)1-6599 900 

România 
SC Bayer SRL 
Tel: +40 21 529 59 00 

Ireland 
Bayer Limited 
Tel: +353 1 2999313 

Slovenija 
Bayer d. o. o. 
Tel: +386 (0)1 58 14 400 

Ísland 
Icepharma hf. 
Sími: +354 540 8000 

Slovenská republika 
Bayer spol. s r.o. 
Tel. +421 2 59 21 31 11 

Italia 
Bayer S.p.A. 
Tel: +39 02 397 8 1 

Suomi/Finland 
Bayer Oy 
Puh/Tel: +358- 20 785 21 

Κύπρος 
NOVAGEM Limited 
Tηλ: +357 22 48 38 58 

Sverige 
Bayer AB 
Tel: +46 (0) 8 580 223 00 

Latvija 
SIA Bayer 
Tel: +371 67 84 55 63 

United Kingdom 
Bayer plc 
Tel: +44-(0)118 206 3000 

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



78 

Detailed instructions for reconstitution and administration of Jivi 
You will need alcohol swabs, gauze pads, plasters and tourniquet. These items are not included in the 
Jivi package. 
 
1. Wash your hands thoroughly using soap and warm water. 
 
2. Hold an unopened vial and also a syringe in your hands to warm it to a comfortable temperature 

(do not exceed 37 °C). 
 
3. Remove the protective cap from the vial (A). Wipe the rubber stopper on the 

vial with an alcohol swab and allow the stopper to air dry before use. 
 

 
4. Place the powder vial on a firm, non-slip surface. Peel off the paper cover on 

the plastic housing of the vial adapter. Do not remove the adapter from the 
plastic housing. Holding the adapter housing, place over the product vial and 
firmly press down (B). The adapter will snap over the vial cap. Do not 
remove the adapter housing at this point. 

  
5. Hold the pre-filled syringe of solvent upright. Grasp the plunger rod as per 

the diagram and attach the rod by turning it firmly clockwise into the 
threaded stopper (C). 

 

 
6. Holding the syringe by the barrel, snap the syringe cap off the tip (D). Do not 

touch the syringe tip with your hand or any surface. Set the syringe aside for 
further use. 

 

 
7. Now remove and discard the adapter housing (E). 
 

 
8. Attach the pre-filled syringe to the threaded vial adapter by turning 

clockwise (F). 
 

 
9. Inject the solvent by slowly pushing down on the plunger rod (G). 
 

 
10. Swirl vial gently until all material is dissolved (H). Do not shake vial. Be sure 

that the powder is completely dissolved. Look to check there are no particles 
or discoloration before you use the solution. Do not use solutions containing 
visible particles or that are cloudy. 

 
 



79 

11. Hold the vial on end above the vial adapter and syringe (I). Fill the syringe 
by drawing the plunger out slowly and smoothly. Ensure that the full content 
of the vial is drawn into the syringe. Hold the syringe upright and push the 
plunger until no air is left in the syringe. 

 
 

12. Apply a tourniquet to your arm. 
 
13. Determine the point of injection and clean the skin. 
 
14. Puncture the vein and secure the venipuncture set with a plaster. 
 
15. Holding the vial adapter in place, remove the syringe from the vial adapter 

(the adapter should remain attached to the vial). Attach the syringe to the 
venipuncture set (J). Ensure that no blood enters the syringe  

 

 
16. Remove tourniquet. 
 
17. Inject the solution into a vein over 2 to 5 minutes, keeping an eye on the position of the needle. 

The speed of injection should be based on your comfort, but should not be faster than 2.5 mL 
per minute. 

 
18. If a further dose is needed, use a new syringe with product reconstituted as described above. 
 
19. If no further dose is required, remove the venipuncture set and syringe. Hold a pad firmly over 

the injection site on your outstretched arm for about 2 minutes. Finally, apply a small pressure 
dressing to the injection site and consider if a plaster is necessary. 

 
20. It is recommended that every time you use Jivi, you note down the name and batch number of 

the product. 
 
21. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist or 

physician how to throw away medicines you no longer use. These measures will help protect the 
environment 

 
 


	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