Adynovi

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

2 

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

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

See section 4.8 for how to report adverse reactions. 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 250 IU / 5 ml powder and solvent for solution for injection 

ADYNOVI 500 IU / 5 ml powder and solvent for solution for injection 

ADYNOVI 1000 IU / 5 ml powder and solvent for solution for injection 

ADYNOVI 2000 IU / 5 ml powder and solvent for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

ADYNOVI 250 IU / 5 ml powder and solvent for solution for injection 

Each vial contains nominally 250 IU human coagulation factor VIII (rDNA), rurioctocog alfa pegol, 

corresponding to a concentration of 50 IU/ml after reconstitution with 5 ml solvent.  

 

ADYNOVI 500 IU / 5 ml powder and solvent for solution for injection 

Each vial contains nominally 500 IU human coagulation factor VIII (rDNA), rurioctocog alfa pegol, 

corresponding to a concentration of 100 IU/ml after reconstitution with 5 ml solvent.  

 

ADYNOVI 1000 IU / 5 ml powder and solvent for solution for injection 

Each vial contains nominally 1000 IU human coagulation factor VIII (rDNA), rurioctocog alfa pegol, 

corresponding to a concentration of 200 IU/ml after reconstitution with 5 ml solvent.  

 

ADYNOVI 2000 IU / 5 ml powder and solvent for solution for injection  

Each vial contains nominally 2000 IU human coagulation factor VIII (rDNA), rurioctocog alfa pegol, 

corresponding to a concentration of 400 IU/ml after reconstitution with 5 ml solvent. 

 

The potency (International Units) is determined using the chromogenic assay. The specific activity of 

ADYNOVI is approximately 4000-6500 IU/mg protein. 

 

The active substance rurioctocog alfa pegol is a covalent conjugate of the protein octocog alfa* with a 

20 kDa polyethylene glycol (PEG).  

 

* Human factor VIII produced by recombinant DNA technology in a Chinese Hamster Ovary (CHO) 

cell line. 

 

Excipient(s) with known effect 

Each powder vial contains 0.45 mmol (10 mg) sodium, see section 4.4. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder and solvent for solution for injection. 

 

Powder: White to off-white friable powder. 

Solvent: Clear and colourless solution. 

 

 



 

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4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment and prophylaxis of bleeding in patients 12 years and above with haemophilia A (congenital 

factor VIII deficiency). 

 

4.2 Posology and method of administration 

 

Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.  

 

Previously untreated patients 

The safety and efficacy of ADYNOVI in previously untreated patients have not yet been established. 

No data are available. 

 

Treatment monitoring 

During the course of treatment, appropriate determination of factor VIII levels is advised to guide the 

dose to be administered and the frequency of repeated infusions. Individual patients may vary in their 

response to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight 

may require adjustment in underweight or overweight patients. In the case of major surgical 

interventions in particular, precise monitoring of the substitution therapy by means of coagulation 

analysis (plasma factor VIII activity) is indispensable.  

A field study has indicated that plasma factor VIII levels can be monitored using either a chromogenic 

substrate assay or a one stage clotting assay routinely used in clinical laboratories. 

 

Posology  

The dose and duration of the substitution therapy depend on the severity of the factor VIII deficiency, 

on the location and extent of the bleeding and on the patient's clinical condition. 

 

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 

International Units (relative to an International Standard for factor VIII in plasma).  

 

One International Unit (IU) of factor VIII activity is equivalent to that quantity of factor VIII in one ml 

of normal human plasma. 

 

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 2 IU/dl. The required 

dose is determined using the following formula: 

 

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

 

The amount to be administered and the frequency of administration should always be oriented to the 

clinical effectiveness in the individual case. 

 

In the case of the following haemorrhagic events, factor VIII activity should not fall below the given 

plasma activity level (in % of normal or IU/dl) in the corresponding period.  

 

The following Table 1 can be used to guide dosing in bleeding episodes and surgery: 

 



 

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Table 1 Guide for dosing in bleeding episodes and surgery 

Degree of haemorrhage/type 

of surgical procedure 

Factor VIII level 

required (% or IU/dl) 

Frequency of doses (hours)/duration 

of therapy (days) 

Haemorrhage   

Early haemarthrosis, muscle 

bleeding or oral bleeding. 

20 – 40 Repeat injections every 12 to 24 hours. 

At least 1 day, until the bleeding 

episode, as indicated by pain, is 

resolved or healing is achieved. 

 

More extensive haemarthrosis, 

muscle bleeding or haematoma 

30 – 60 Repeat injections every 12 to 24 hours 

for 3 – 4 days or more until pain and 

acute disability are resolved. 

 

Life threatening haemorrhages. 60 – 100 Repeat injections every 8 to 24 hours 

until threat is resolved. 

Surgery   

Minor 

Including tooth extraction. 

30 – 60 Every 24 hours at least 1 day, until 

healing is achieved. 

 

Major 80 – 100 

 

(pre- and postoperative) 

Repeat injections every 8 to 24 hours 

until adequate wound healing, then 

continue therapy for at least 

another 7 days to maintain a factor VIII 

activity of 30% to 60% (IU/dl). 

 

Prophylaxis  

 

For long term prophylaxis, the recommended dose is 40 to 50 IU of ADYNOVI per kg bodyweight 

twice weekly in 3 to 4 day intervals. Adjustments of doses and administration intervals may be 

considered based on achieved FVIII levels and individual bleeding tendency (see section 5.2). 

 

Paediatric population  

 

On demand treatment dosing in paediatric patients (12 to 18 years of age) is the same as for adult 

patients. Prophylactic treatment for patients from 12 to <18 years is the same as for adult patients. The 

long-term safety of ADYNOVI in children below 12 years has not yet been established. Adjustments 

of doses and administration intervals may be considered based on achieved FVIII levels and individual 

bleeding tendency (see section 5.2).  

 

Method of administration  

 

ADYNOVI is for intravenous use.  

The rate of administration should be determined to ensure the comfort of the patient up to a maximum 

of 10 ml/min. 

 

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

 

4.3 Contraindications 

 

Hypersensitivity to the active substance, to the parent molecule octocog alfa or to any of the excipients 

listed in section 6.1.  

 

Known allergic reaction to mouse or hamster protein. 

 



 

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4.4 Special warnings and precautions for use 

 

Hypersensitivity  

Allergic type hypersensitivity reactions are possible with ADYNOVI. The medicinal product contains 

traces of mouse and hamster proteins. If symptoms of hypersensitivity occur, patients should be 

advised to discontinue use of the medicinal product immediately and contact their physician. Patients 

should be informed of the early signs of hypersensitivity reactions including hives, generalised 

urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis.  

 

In case of anaphylactic shock, standard medical treatment for shock should be implemented.  

 

Inhibitors  

The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in the 

management of individuals with haemophilia A. These inhibitors are usually IgG immunoglobulins 

directed against the factor VIII procoagulant activity, which are quantified in Bethesda Units (BU) 

per ml of plasma using the modified assay. The risk of developing inhibitors is correlated to the 

severity of the disease as well as the exposure to factor VIII, this risk being highest within the 

first 20 exposure days. Rarely, inhibitors may develop after the first 100 exposure days.  

 

Cases of recurrent inhibitor (low titre) have been observed after switching from one factor VIII 

product to another in previously treated patients with more than 100 exposure days who have a 

previous history of inhibitor development. Therefore, it is recommended to monitor all patients 

carefully for inhibitor occurrence following any product switch.  

 

The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titre 

inhibitors which are transiently present or remain consistently low titre posing less of a risk of 

insufficient clinical response than high titre inhibitors. 

 

In general, all patients treated with coagulation factor VIII products should be carefully monitored for 

the development of inhibitors by appropriate clinical observations and laboratory tests. If the expected 

factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate 

dose, testing for factor VIII inhibitor presence should be performed. In patients with high levels of 

inhibitor, factor VIII therapy may not be effective and other therapeutic options should be considered. 

Management of such patients should be directed by physicians with experience in the care of 

haemophilia and factor VIII inhibitors. 

 

Immune tolerance induction (ITI) 

No clinical data for use of ADYNOVI in ITI are available. 

 

Cardiovascular events 

In patients with existing cardiovascular risk factors, substitution therapy with factor VIII may increase 

the cardiovascular risk. 

 

Catheter-related complications in treatment 

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. 

 

Excipient related considerations 

After reconstitution this medicinal product contains 0.45 mmol sodium (10 mg) per vial. To be taken 

into consideration by patients on a controlled sodium diet. 

 

Name and batch number of the medicinal product 

It is strongly recommended that every time that ADYNOVI is administered to a patient, the name and 

batch number of the product are recorded in order to maintain a link between the patient and the batch 

of the medicinal product. 

 



 

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Paediatric population  

The listed warnings and precautions apply both to adults and children. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No interactions of human coagulation factor VIII (rDNA) products with other medicinal products have 

been reported. 

 

4.6 Fertility, pregnancy and lactation 

 

Animal reproduction studies have not been conducted with factor VIII. Based on the rare occurrence 

of haemophilia A in women, experience regarding the use of factor VIII during pregnancy and 

breast-feeding is not available. Therefore, factor VIII should be used during pregnancy and lactation 

only if clearly indicated. 

 

4.7 Effects on ability to drive and use machines 

 

ADYNOVI 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, generalised urticaria, headache, hives, hypotension, lethargy, nausea, 

restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed 

rarely and may in some cases progress to severe anaphylaxis (including shock).  

 

Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated 

with factor VIII, including with ADYNOVI. If such inhibitors occur, the condition will manifest itself 

as an insufficient clinical response. In such cases, it is recommended that a specialised haemophilia 

centre be contacted. 

 

Tabulated list of adverse reactions  

The safety of ADYNOVI was evaluated in 243 previously treated patients with severe haemophilia A 

(factor VIII less than 1% of normal), who received at least one dose of ADYNOVI in 3 completed 

multi-center, prospective, open label clinical studies and 2 ongoing clinical studies. The median 

number of exposure days to ADYNOVI per subject was 103.5 (min-max: 1- 278).  

 

The table presented below is according to the MedDRA system organ classification (System Organ 

Class and Preferred Term Level).  

 

Frequencies have been evaluated according to the following convention: very common (≥1/10); 

common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare 

(<1/10,000), not known (cannot be estimated from the available data). Within each frequency 

grouping, adverse reactions are presented in order of decreasing seriousness. 

 



 

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Table 2: Adverse reactions reported for ADYNOVI  

MedDRA 

Standard System Organ Class 

Adverse reactions 

 

Frequency per patient 

 

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

Immune system disorders Hypersensitivity Uncommon 

Nervous system disorders Headache Common 

Vascular disorders Flushing Uncommon 

Gastrointestinal disorders Diarrhoea Common 

Nausea Common 

Skin and subcutaneous tissue disorders Rash Common 

* Frequency is based on studies with all FVIII products which included patients with severe 

haemophilia A. PTPs = previously-treated patients. 

 

Description of selected adverse reactions  

 

Hypersensitivity 

The observed event of hypersensitivity was a mild transient non-serious rash, occurring in 

one 2-year-old patient who had developed a previous rash while on ADYNOVI. 

 

Paediatric population 

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. 

The safety of ADYNOVI was evaluated in 38 subjects < 6 years and 34 subjects 6 to < 12 years of age 

having accumulated a total of 2880 EDs and 2975 EDs respectively. The mean (SD) age 

was 3.3 (1.55) and 8.1 (1.92) years respectively. 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V 

 

4.9 Overdose 

 

No symptoms of overdose with recombinant coagulation factor VIII have been reported. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor VIII, ATC code: B02BD02. 

 

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 haemophilic 

patient, factor VIII binds to von Willebrand factor in the patient’s circulation. Activated factor VIII 

acts as a cofactor for activated factor IX, accelerating the conversion of factor X to activated factor X. 

Activated factor X converts prothrombin into thrombin. Thrombin then converts fibrinogen into fibrin 

and a clot can be formed. Haemophilia A is a X-chromosomal linked hereditary disorder of blood 

coagulation due to decreased levels of factor VIII:C and results in profuse bleeding into joints, 

muscles or internal organs, either spontaneously or as results of accidental or surgical trauma. By 

replacement therapy the plasma levels of factor VIII are increased, thereby enabling a temporary 

correction of the factor deficiency and correction of the bleeding tendencies. 

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


 

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Rurioctocog alfa pegol, is a pegylated recombinant human factor VIII with an extended half-life. 

Rurioctocog alfa pegol is a covalent conjugate of octocog alfa consisting of 2,332 amino acids with 

polyethylene glycol (PEG) reagent (MW 20 kDa). The therapeutic activity of rurioctocog alfa pegol is 

derived from octocog alfa, which is produced by recombinant DNA technology from a Chinese 

hamster ovary cell line. Octocog alfa is then covalently conjugated with the PEG reagent. The PEG 

moiety is conjugated to octocog alfa to increase the plasma half-life.  

 

Clinical efficacy and safety 

The safety, efficacy, and pharmacokinetics of ADYNOVI were evaluated in a pivotal multicenter, 

open-label, prospective clinical trial that compared the efficacy of a twice weekly prophylactic 

treatment regimen to on-demand treatment and determined haemostatic efficacy in the treatment of 

bleeding episodes. A total of 137 male PTPs (12 to 65 years of age) with severe haemophilia A 

received at least one infusion with ADYNOVI. Twenty-five of the 137 subjects were adolescents 

(12 to less than 18 years of age). 

 

Prophylactic treatment 

Subjects received either prophylactic treatment (n = 120) with ADYNOVI at a dose of 40-50 IU 

per kg twice weekly or on-demand treatment (n = 17) with ADYNOVI at a dose of 10-60 IU per kg 

for a 6-month period. The median dosing interval was 3.6 days and the mean dose (SD) 

was 48.7 (4.4) IU/kg. One hundred eighteen of 120 (98%) prophylaxis subjects remained on the 

starting recommended regimen without dose adjustment, and 2 subjects increased their dose 

to 60 IU/kg during prophylaxis due to bleeding in target joints.  

 

In the per-protocol population, i.e. dosed according to the protocol specific dosing requirements, a 

total of 101 subjects received a twice a week regimen in the prophylaxis arm, and 17 subjects were 

treated episodically in the on-demand arm. The median annualised bleed rate (ABR) in the on-demand 

treatment arm was 41.5 compared to 1.9 while on a twice a week prophylaxis regimen. The median 

joint ABR (Q1 ; Q3) in the on-demand arm was 38.1 (24.5 ; 44.6) compared to 0.0 (0.0 ; 2.0) while on 

prophylaxis, and the median spontaneous ABR was 21.6 (11.2 ; 33.2) on the on-demand arm 

compared to 0.0 (0.0 ; 2.2) while on prophylaxis. Results for the full-analysis population were similar 

to those for the per-protocol population. Of note, ABR is not comparable between different factor 

concentrates and between different clinical studies. 

 

Forty out of 101 subjects (40%) experienced no bleeding episodes, 58 out of 101 subjects (57%) 

experienced no joint bleeding episodes, and 58 out of 101 subjects (57%) experienced no spontaneous 

bleeding episodes in the prophylaxis arm. All subjects in the on-demand arm experienced a bleeding 

episode, including a joint or spontaneous bleeding episode. 

 

Treatment of bleeding episodes 

A total of 518 bleeding episodes were treated with ADYNOVI in the per-protocol population. Of 

these, 361 bleeding episodes (n=17 subjects) occurred in the on-demand arm and 157 (n=61 subjects) 

occurred in the prophylaxis arm. The median dose per infusion to treat all bleeding episodes in the 

per-protocol population was 32.0 (Interquartile Range (IQR): 21.5) IU per kg. Overall, 95.9% of 

bleeding episodes were controlled with 1 to 2 infusions and 85.5% were controlled with 

only 1 infusion. Of the 518 bleeding episodes, 96.1% were rated excellent (full relief of pain and 

cessation of objective signs of bleeding after a single infusion) or good (definite pain relief and/or 

improvement in signs of bleeding after a single infusion) in their response to treatment with 

ADYNOVI. 

 

Paediatric population < 12 years of age 

A total of 66 PTPs with severe haemophilia A were dosed (32 subjects aged < 6 years and 34 subjects 

aged 6 to < 12 years) in the paediatric study. The prophylactic regimen was 40 to 60 IU/kg of 

ADYNOVI twice a week. The mean dose (SD) was 54.3 (6.3) IU/kg and the median frequency of 

infusions per week was 1.87. The median overall ABR was 2.0 (IQR: 3.9) for the 65 subjects in the 

per-protocol population and the median ABRs for spontaneous and joint bleeding episodes were 

both 0 (IQR: 1.9). Twenty four out of 65 subjects (37%) experienced no bleeding episodes, 47 out 



 

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of 65 subjects (72%) experienced no joint bleeding episodes, and 43 out of 65 subjects (66%) 

experienced no spontaneous bleeding episodes on prophylaxis. 

 

Of the 70 bleeding episodes observed during the paediatric study, 82.9% were controlled 

with 1 infusion and 91.4% were controlled with 1 or 2 infusions. Control of bleeding was rated 

excellent (full relief of pain and cessation of objective signs of bleeding after a single infusion) or 

good (definite pain relief and/or improvement in signs of bleeding after a single infusion) in 63 out 

of 70 (90.0%) bleeding episodes.  

 

Perioperative management (surgical prophylaxis) 

A total of 21 major surgical procedures and 5 additional minor surgeries were performed and assessed 

in 21 unique subjects in the surgery study. For major surgeries, the preoperative loading dose ranged 

from 36 IU/kg to 109 IU/kg (median: 63 IU/kg); and postoperative total dose ranged from 186 IU/kg 

to 1320 IU/kg (median: 490 IU/kg). The median total dose for major surgeries was 553 IU/kg 

(range: 248-1394 IU/kg) and the median total dose of minor surgeries was 106 IU/kg (range: 76-

132 IU/kg). 

 

Perioperative haemostatic efficacy was rated as excellent (blood loss less than or equal to that 

expected for the same type of procedure performed in a non-haemophilic patient, and required blood 

components for transfusions less than or similar to that expected in non-haemophilic population) for 

all 26 (21 major, 5 minor) procedures. The median (IQR) observed intraoperative blood loss (n = 14) 

was 10.0 (20.0) ml compared to the predicted average blood loss (n = 14) of 150.0 (140.0) ml for 

major orthopaedic surgeries. 

 

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

ADYNOVI in one or more subsets of the paediatric population in the treatment of congenital 

factor VIII deficiency. See 4.2 for information on paediatric use. 

 

5.2 Pharmacokinetic properties 

 

The pharmacokinetics (PK) of ADYNOVI were evaluated in a crossover study with octocog alfa 

in 26 subjects (18 adults and 8 adolescents) and in 22 subjects (16 adults and 6 adolescents) 

after 6 months of treatment with ADYNOVI. Plasma factor VIII activity was measured by the 

one stage clotting assay and chromogenic assay. 

 

ADYNOVI has an extended half-life of 1.4 to 1.5-fold compared to recombinant human coagulation 

factor VIII (octocog alfa) in the adolescent and adult population, as determined based on one stage 

clotting and chromogenic assays, respectively. An increase in AUC and a decrease in clearance as 

compared to the parent molecule, octocog alfa, were also observed. Incremental recovery was 

comparable with both products. The change in PK parameters was similar in both the adult and 

adolescent populations and between one-stage clotting and chromogenic substrate assays. 

 

Paediatric pharmacokinetics 

Pharmacokinetic parameters calculated from 39 subjects less than 18 years of age (intent-to-treat 

analysis) are available for 14 children (2 to less than 6 years), 17 older children (6 to less 

than 12 years) and 8 adolescent subjects (12 to < 18 years of age). The half-life extension in the 

paediatric population was 1.3 to 1.5 fold using both the one stage clotting and chromogenic assays. 

The mean clearance (based on body weight) of ADYNOVI was higher and the mean half-life was 

lower in children less than 12 years of age than adults.  

A higher dose may be required in children less than 12 years of age, see section 4.2.  

 



 

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Table 3: Pharmacokinetic parameters using the chromogenic assay 

(Arithmetic mean ± SD) 

PK parameters 

ADYNOVI 

Adults 

(18 years and 

older) 

N = 18 

Dose:  

45 ± 5 IU/kg 

ADYNOVI 

Adolescents 

(12-<18 years) 

N = 8 

Dose:  

45 ± 5 IU/kg 

ADYNOVI 

Paediatric 

patients 

(6-<12 years) 

N = 17 

Dose:  

50 ± 10 IU/kg 

ADYNOVI 

Paediatric 

patients 

(< 6 years) 

N = 14 

Dose:  

50 ± 10 IU/kg 

Design Individual PK with full samplinga Population PK with sparse sampling
b 

Terminal 

half--life [h] 
15.01 ± 3.89 13.80 ± 4.01 11.93 ± 2.58 12.99 ± 8.75 

MRT [h] 19.70 ± 5.05 17.73 ± 5.44 17.24 ± 3.73 18.74 ± 12.60 

CL [mL/(kg·h)]d 2.16 ± 0.75 2.58 ± 0.84 2.80 ± 0.67 3.49 ± 1.21 

Incremental 

recovery 

[(IU/dL)/(IU/kg)] 

2.87 ± 0.61 2.34 ± 0.62 
nac 

(2.19± 0.40) 

nac 

(1.90 ± 0.27) 

AUC0-Inf 

[IU·h/dL] 
2589 ± 848 1900 ± 841 2259 ± 514 2190 ± 1593 

Vss [dL/kg] 0.40 ± 0.09 0.54 ± 0.22 0.46 ± 0.04 0.54 ± 0.03 

Cmax [IU/dL] 145 ± 29 117 ± 28 
nac 

(130 ± 24) 

nac 

(117 ± 16) 

Abbreviations: Cmax: maximum observed activity; AUC: area under the curve; MRT: mean residence 

time; CL: clearance; Vss: body weight adjusted volume of distribution at steady-state,  
a Individual PK with 12 post-infusion samples. 
b Population PK model with 3 post-infusion samples based on randomized drawing schedule. 
c NA, Not applicable, as Incremental Recovery and Cmax in children were determined by individual 

PK. Results for Incremental Recovery and Cmax determined by individual PK in parenthesis. 
d The clearance value of 12.18 ml/(kg·h) for subject 122001 in age group 12 to < 18 years was not 

included in the analysis of clearance. 

 

5.3 Preclinical safety data 

 

In the repeat dose toxicity study in Cynomologous monkey, two animals showed vacuolation in the 

kidney in the mid dose group (350IU/kg). The vacuolations did not recover after 2 weeks. The human 

relevance of kidney vacuolation observed in the preclinical study is unknown. 

 

Nonclinical data are limited to 1 month exposure and no studies in juvenile animals were conducted 

with ADYNOVI. Thus it was not possible to conclude on the potential risks of PEG accumulation in 

various tissues/organs relevant for chronic use of ADYNOVI in the paediatric population.  

No studies on genotoxicity, carcinogenicity or reproductive toxicity have been performed with 

ADYNOVI. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Powder 

Mannitol  

Trehalose dihydrate  

Histidine  

Glutathione  

Sodium chloride  

Calcium chloride dihydrate 



 

11 

Tris(hydroxymethyl)aminomethane  

Polysorbate 80  

 

Solvent 

Sterilised water for injections 

 

6.2 Incompatibilities 

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 

products.  

 

6.3 Shelf life 

 

Unopened vial 

2 years.  

 

Before opening the product may be stored at room temperature (up to 30 °C) for a period of up 

to 3 months. The end of the 3-month storage at room temperature should be recorded on the product 

carton. This date should never exceed the one initially mentioned on the outer carton. At the end of 

this period the product shall not be put back in the refrigerator, but shall be used or discarded. 

 

After reconstitution 

Chemical and physical in-use stability has been demonstrated for 3 hours at a temperature not 

above 30 °C. From a microbiological point of view, unless the method of reconstitution precludes the 

risk of microbial contamination, the product should be used immediately. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. Do not refrigerate. 

 

6.4 Special precautions for storage 

 

Store refrigerated (2°to 8 °C). 

Do not freeze. 

ADYNOVI with BAXJECT II Hi-Flow device: Keep the vial in the outer carton in order to protect 

from light. 

ADYNOVI in BAXJECT III system: Keep the sealed blister in the outer carton in order to protect 

from light. 

 

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

 

6.5 Nature and contents of container  

 

Type I glass vial, closed with a chlorobutyl rubber stopper, containing 250 IU, 500 IU, 1000 IU or 

2000 IU of powder. 

Type I glass vial, closed with a chlorobutyl rubber stopper, containing 5 ml of sterilised water for 

injections. 

The medicinal product is provided in one of the following configurations: 

 

- ADYNOVI with BAXJECT II Hi-Flow device: Each pack contains a powder vial, a solvent vial 
and a device for reconstitution (BAXJECT II Hi-Flow). 

- ADYNOVI in BAXJECT III system: Each pack contains a ready to use BAXJECT III system in 
a sealed blister, withthe powder vial and the solvent vial preassembled for reconstitution. 

 

6.6 Special precautions for disposal and other handling 

 

The reconstituted medicinal product should be inspected visually for particulate matter and 

discoloration prior to administration. The solution should be clear or slightly opalescent. Solutions that 

are cloudy or have deposits should not be used.  

After reconstitution, the solution has a pH of 6.7 to 7.3. The osmolality is ≥ 380 mOsmol/kg. 



 

12 

 

Preparation and reconstitution using the BAXJECT II Hi-Flow device 

For reconstitution use only the solvent vial and the reconstitution device provided in the pack. 

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

reconstitution procedure. 

2. Allow the vials of powder and solvent to reach room temperature (between 15 °C and 25 °C) 

before use. 

3. Remove plastic caps from the powder and solvent vials. 

4. Clean rubber stoppers with an alcohol wipe and allow to dry prior to use. 

5. Open the BAXJECT II Hi-Flow device package by peeling away the lid, without touching the 

inside (Figure A). Do not remove the device from the package. 

6. Turn the package over. Press straight down to fully insert the clear plastic spike through the 

solvent vial stopper (Figure B).  

7. Grip the BAXJECT II Hi-Flow package at its edge and pull the package off the device 

(Figure C). Do not remove the blue cap from the BAXJECT II Hi-Flow device. Do not touch 

the exposed purple plastic spike. 

8. Turn the system over so that the solvent vial is on top. Quickly insert the purple plastic spike 

fully into the powder vial stopper by pushing straight down (Figure D). The vacuum will draw 

the solvent into the powder vial. 

9. Swirl gently until the powder is completely dissolved. Do not refrigerate after reconstitution. 

 

Figure A Figure B Figure C 

   
Figure D Figure E Figure F 

   
 

Administration 

• Visually inspect the reconstituted solution for particulate matter and discoloration prior to 
administration.  

o The appearance of the reconstituted solution is clear and colourless.  
o Do not use if particulate matter or discoloration is observed. 

• Administer as soon as possible, but no later than 3 hours after reconstitution.  
 

Administration Steps: 

 

1. Remove the blue cap from the BAXJECT II Hi-Flow device (Figure E). Do not draw air into 

the syringe. Connect the syringe to the BAXJECT II Hi-Flow. Use of a Luer-lock syringe is 

recommended.  



 

13 

2. Turn the system upside down (powder vial now on top). Draw the reconstituted solution into the 

syringe by pulling the plunger back slowly (Figure F).  

3. Disconnect the syringe; attach a suitable needle and inject intravenously. If a patient is to 

receive more than one vial of ADYNOVI, the contents of multiple vials may be drawn into the 

same syringe.  

A separate BAXJECT II Hi-Flow device is required to reconstitute each vial of ADYNOVI with 

the solvent. 

4. Administer over a period of up to 5 minutes (maximum infusion rate 10 ml per min).  

 

It is strongly recommended that every time ADYNOVI is administered, the name and batch number of 

the product are recorded. Peel-off labels are provided on the powder vial. 

 

Reconstitution with the BAXJECT III system 

Do not use if the lid is not completely sealed on the blister 

 

1. If the product is still stored in a refrigerator, take the sealed blister (contains powder and solvent 

vials preassembled with the system for reconstitution) from the refrigerator and let it reach room 

temperature (between 15 °C and 25 °C). 

2. Wash your hands thoroughly using soap and warm water. 

3. Open the ADYNOVI blister by peeling away the lid. Remove the BAXJECT III system from 

the blister. 

4. Place the powder vial on a flat surface with the solvent vial on top (Figure 1). The solvent vial 

has a blue stripe. Do not remove the blue cap until instructed in a later step. 

5. With one hand holding the powder vial in the BAXJECT III system, press down firmly on the 

solvent vial with the other hand until the system is fully collapsed and the solvent flows down 

into the powder vial (Figure 2). Do not tilt the system until the transfer is complete. 

6. Verify that the solvent transfer is complete. Swirl gently until all material is dissolved 

(Figure 3). Be sure that the powder is completely dissolved, otherwise not all reconstituted 

solution will pass through the device filter. The product dissolves rapidly (usually in less 

than 1 minute). After reconstitution the solution should be clear, colourless and free from 

particles. 

 

Figure 1 Figure 2 Figure 3 

   
 

Administration 

• Visually inspect the reconstituted solution for particulate matter and discoloration prior to 
administration.  

o The appearance of the reconstituted solution is clear and colourless.  
o Do not use if particulate matter or discoloration is observed. 

• Administer as soon as possible, but no later than 3 hours after reconstitution.  
 

Administration Steps: 

 

1. Remove the blue cap from the BAXJECT III device. Do not draw air into the syringe. 

Connect the syringe to the BAXJECT III device. Use of a Luer-lock syringe is recommended.  

2. Turn the system upside down (powder vial now on top). Draw the reconstituted solution into the 

syringe by pulling the plunger back slowly.  



 

14 

3. Disconnect the syringe; attach a suitable needle and inject intravenously. If a patient is to 

receive more than one vial of ADYNOVI, the contents of multiple vials may be drawn into the 

same syringe.  

4. Administer over a period of up to 5 minutes (maximum infusion rate 10 ml per min).  

 

It is strongly recommended that every time ADYNOVI is administered, the name and batch number of 

the product are recorded. Peel-off labels are provided on the blister. 

 

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

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH  

Industriestrasse 67  

A-1221 Vienna  

Austria 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/17/1247/003 

EU/1/17/1247/004 

EU/1/17/1247/007 

EU/1/17/1247/008 

EU/1/17/1247/011 

EU/1/17/1247/012 

EU/1/17/1247/013 

EU/1/17/1247/014 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 08 January 2018 

 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

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

 

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


 

15 

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 

 

ADYNOVI 250 IU / 2 ml powder and solvent for solution for injection 

ADYNOVI 500 IU / 2 ml powder and solvent for solution for injection 

ADYNOVI 1000 IU / 2 ml powder and solvent for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

ADYNOVI 250 IU / 2 ml powder and solvent for solution for injection 

Each vial contains nominally 250 IU human coagulation factor VIII (rDNA), rurioctocog alfa pegol, 

corresponding to a concentration of 125 IU/ml after reconstitution with 2 ml solvent. 

 

ADYNOVI 500 IU / 2 ml powder and solvent for solution for injection 

Each vial contains nominally 500 IU human coagulation factor VIII (rDNA), rurioctocog alfa pegol, 

corresponding to a concentration of 250 IU/ml after reconstitution with 2 ml solvent. 

 

ADYNOVI 1000 IU / 2 ml powder and solvent for solution for injection 

Each vial contains nominally 1000 IU human coagulation factor VIII (rDNA), rurioctocog alfa pegol, 

corresponding to a concentration of 500 IU/ml after reconstitution with 2 ml solvent. 

 

The potency (International Units) is determined using the chromogenic assay. The specific activity of 

ADYNOVI is approximately 4000-6500 IU/mg protein. 

 

The active substance rurioctocog alfa pegol is a covalent conjugate of the protein octocog alfa* with a 

20 kDa polyethylene glycol (PEG).  

 

* Human factor VIII produced by recombinant DNA technology in a Chinese Hamster Ovary (CHO) 

cell line. 

 

Excipient(s) with known effect 

Each powder vial contains 0.45 mmol (10 mg) sodium, see section 4.4. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder and solvent for solution for injection. 

 

Powder: White to off-white friable powder. 

Solvent: Clear and colourless solution. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment and prophylaxis of bleeding in patients 12 years and above with haemophilia A (congenital 

factor VIII deficiency). 

 



 

16 

4.2 Posology and method of administration 

 

Treatment should be under the supervision of a physician experienced in the treatment of haemophilia.  

 

Previously untreated patients 

The safety and efficacy of ADYNOVI in previously untreated patients have not yet been established. 

No data are available. 

 

Treatment monitoring: 

During the course of treatment, appropriate determination of factor VIII levels is advised to guide the 

dose to be administered and the frequency of repeated infusions. Individual patients may vary in their 

response to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight 

may require adjustment in underweight or overweight patients. In the case of major surgical 

interventions in particular, precise monitoring of the substitution therapy by means of coagulation 

analysis (plasma factor VIII activity) is indispensable.  

A field study has indicated that plasma factor VIII levels can be monitored using either a chromogenic 

substrate assay or a one stage clotting assay routinely used in clinical laboratories. 

 

Posology  

The dose and duration of the substitution therapy depend on the severity of the factor VIII deficiency, 

on the location and extent of the bleeding and on the patient's clinical condition. 

 

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 

International Units (relative to an International Standard for factor VIII in plasma).  

 

One International Unit (IU) of factor VIII activity is equivalent to that quantity of factor VIII in one ml 

of normal human plasma. 

 

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 2 IU/dl. The required 

dose is determined using the following formula: 

 

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

 

The amount to be administered and the frequency of administration should always be oriented to the 

clinical effectiveness in the individual case. 

 

In the case of the following haemorrhagic events, factor VIII activity should not fall below the given 

plasma activity level (in % of normal or IU/dl) in the corresponding period.  

 

The following Table 1 can be used to guide dosing in bleeding episodes and surgery: 

 



 

17 

Table 1 Guide for dosing in bleeding episodes and surgery 

Degree of haemorrhage/type 

of surgical procedure 

Factor VIII level 

required (% or IU/dl) 

Frequency of doses (hours)/duration 

of therapy (days) 

Haemorrhage   

Early haemarthrosis, muscle 

bleeding or oral bleeding. 

20 – 40 Repeat injections every 12 to 24 hours. 

At least 1 day, until the bleeding 

episode, as indicated by pain, is 

resolved or healing is achieved. 

 

More extensive haemarthrosis, 

muscle bleeding or haematoma 

30 – 60 Repeat injections every 12 to 24 hours 

for 3 – 4 days or more until pain and 

acute disability are resolved. 

 

Life threatening haemorrhages. 60 – 100 Repeat injections every 8 to 24 hours 

until threat is resolved. 

Surgery   

Minor 

Including tooth extraction. 

30 – 60 Every 24 hours at least 1 day, until 

healing is achieved. 

 

Major 80 – 100 

 

(pre- and postoperative) 

Repeat injections every 8 to 24 hours 

until adequate wound healing, then 

continue therapy for at least 

another 7 days to maintain a factor VIII 

activity of 30% to 60% (IU/dl). 

 

Prophylaxis  

 

For long term prophylaxis, the recommended dose is 40 to 50 IU of ADYNOVI per kg bodyweight 

twice weekly in 3 to 4 day intervals. Adjustments of doses and administration intervals may be 

considered based on achieved FVIII levels and individual bleeding tendency (see section 5.2). 

 

Paediatric population  

 

On demand treatment dosing in paediatric patients (12 to 18 years of age) is the same as for adult 

patients. Prophylactic treatment for patients from 12 to <18 years is the same as for adult patients. The 

long-term safety of ADYNOVI in children below 12 years has not yet been established. Adjustments 

of doses and administration intervals may be considered based on achieved FVIII levels and individual 

bleeding tendency (see section 5.2).  

 

Method of administration  

 

ADYNOVI is for intravenous use 

The rate of administration should be determined to ensure the comfort of the patient up to a maximum 

of 10 ml/min. 

 

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

 

4.3 Contraindications 

 

Hypersensitivity to the active substance, to the parent molecule octocog alfa or to any of the excipients 

listed in section 6.1.  

 

Known allergic reaction to mouse or hamster protein. 

 



 

18 

4.4 Special warnings and precautions for use 

 

Hypersensitivity  

Allergic type hypersensitivity reactions are possible with ADYNOVI. The medicinal product contains 

traces of mouse and hamster proteins. If symptoms of hypersensitivity occur, patients should be 

advised to discontinue use of the medicinal product immediately and contact their physician. Patients 

should be informed of the early signs of hypersensitivity reactions including hives, generalised 

urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis.  

 

In case of anaphylactic shock, standard medical treatment for shock should be implemented.  

 

Inhibitors  

The formation of neutralising antibodies (inhibitors) to factor VIII is a known complication in the 

management of individuals with haemophilia A. These inhibitors are usually IgG immunoglobulins 

directed against the factor VIII procoagulant activity, which are quantified in Bethesda Units (BU) 

per ml of plasma using the modified assay. The risk of developing inhibitors is correlated to the 

severity of the disease as well as the exposure to factor VIII, this risk being highest within the 

first 20 exposure days. Rarely, inhibitors may develop after the first 100 exposure days.  

 

Cases of recurrent inhibitor (low titre) have been observed after switching from one factor VIII 

product to another in previously treated patients with more than 100 exposure days who have a 

previous history of inhibitor development. Therefore, it is recommended to monitor all patients 

carefully for inhibitor occurrence following any product switch.  

 

The clinical relevance of inhibitor development will depend on the titre of the inhibitor, with low titre 

inhibitors which are transiently present or remain consistently low titre posing less of a risk of 

insufficient clinical response than high titre inhibitors. 

 

In general, all patients treated with coagulation factor VIII products should be carefully monitored for 

the development of inhibitors by appropriate clinical observations and laboratory tests. If the expected 

factor VIII activity plasma levels are not attained, or if bleeding is not controlled with an appropriate 

dose, testing for factor VIII inhibitor presence should be performed. In patients with high levels of 

inhibitor, factor VIII therapy may not be effective and other therapeutic options should be considered. 

Management of such patients should be directed by physicians with experience in the care of 

haemophilia and factor VIII inhibitors. 

 

Immune tolerance induction (ITI) 

No clinical data for use of ADYNOVI in ITI are available. 

 

Cardiovascular events 

In patients with existing cardiovascular risk factors, substitution therapy with factor VIII may increase 

the cardiovascular risk. 

 

Catheter-related complications in treatment 

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. 

 

Excipient related considerations 

After reconstitution this medicinal product contains 0.45 mmol sodium (10 mg) per vial. To be taken 

into consideration by patients on a controlled sodium diet. 

 

Name and batch number of the medicinal product 

It is strongly recommended that every time that ADYNOVI is administered to a patient, the name and 

batch number of the product are recorded in order to maintain a link between the patient and the batch 

of the medicinal product. 

 



 

19 

Paediatric population  

The listed warnings and precautions apply both to adults and children. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

No interactions of human coagulation factor VIII (rDNA) products with other medicinal products have 

been reported. 

 

4.6 Fertility, pregnancy and lactation 

 

Animal reproduction studies have not been conducted with factor VIII. Based on the rare occurrence 

of haemophilia A in women, experience regarding the use of factor VIII during pregnancy and 

breast-feeding is not available. Therefore, factor VIII should be used during pregnancy and lactation 

only if clearly indicated. 

 

4.7 Effects on ability to drive and use machines 

 

ADYNOVI 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, generalised urticaria, headache, hives, hypotension, lethargy, nausea, 

restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed 

rarely and may in some cases progress to severe anaphylaxis (including shock).  

 

Development of neutralising antibodies (inhibitors) may occur in patients with haemophilia A treated 

with factor VIII, including with ADYNOVI. If such inhibitors occur, the condition will manifest itself 

as an insufficient clinical response. In such cases, it is recommended that a specialised haemophilia 

centre be contacted. 

 

Tabulated list of adverse reactions  

The safety of ADYNOVI was evaluated in 243 previously treated patients with severe haemophilia A 

(factor VIII less than 1% of normal), who received at least one dose of ADYNOVI in 3 completed 

multi-center, prospective, open label clinical studies and 2 ongoing clinical studies. The median 

number of exposure days to ADYNOVI per subject was 103.5 (min-max: 1-278).  

 

The table presented below is according to the MedDRA system organ classification (System Organ 

Class and Preferred Term Level).  

 

Frequencies have been evaluated according to the following convention: very common (≥1/10); 

common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare 

(<1/10,000), not known (cannot be estimated from the available data). Within each frequency 

grouping, adverse reactions are presented in order of decreasing seriousness. 

 



 

20 

Table 2: Adverse reactions reported for ADYNOVI  

MedDRA 

Standard System Organ Class 

Adverse reactions 

 

Frequency per patient 

 

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

Immune system disorders Hypersensitivity Uncommon 

Nervous system disorders Headache Common 

Vascular disorders Flushing Uncommon 

Gastrointestinal disorders Diarrhoea Common 

Nausea Common 

Skin and tubcutaneous Tissue disorders Rash Common 

* Frequency is based on studies with all FVIII products which included patients with severe 

haemophilia A. PTPs = previously-treated patients. 

 

Description of selected adverse reactions  

 

Hypersensitivity 

The observed event of hypersensitivity was a mild transient non-serious rash, occurring in 

one 2-year-old patient who had developed a previous rash while on ADYNOVI. 

 

Paediatric population 

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. 

The safety of ADYNOVI was evaluated in 38 subjects < 6 years and 34 subjects 6 to < 12 years of age 

having accumulated a total of 2880 EDs and 2975 EDs respectively. The mean (SD) age 

was 3.3 (1.55) and 8.1 (1.92) years respectively. 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V 

 

4.9 Overdose 

 

No symptoms of overdose with recombinant coagulation factor VIII have been reported. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor VIII, ATC code: B02BD02. 

 

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 haemophilic 

patient, factor VIII binds to von Willebrand factor in the patient’s circulation. Activated factor VIII 

acts as a cofactor for activated factor IX, accelerating the conversion of factor X to activated factor X. 

Activated factor X converts prothrombin into thrombin. Thrombin then converts fibrinogen into fibrin 

and a clot can be formed. Haemophilia A is a X-chromosomal linked hereditary disorder of blood 

coagulation due to decreased levels of factor VIII:C and results in profuse bleeding into joints, 

muscles or internal organs, either spontaneously or as results of accidental or surgical trauma. By 

replacement therapy the plasma levels of factor VIII are increased, thereby enabling a temporary 

correction of the factor deficiency and correction of the bleeding tendencies. 

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


 

21 

 

Rurioctocog alfa pegol, is a pegylated recombinant human factor VIII with an extended half-life. 

Rurioctocog alfa pegol is a covalent conjugate of octocog alfa consisting of 2,332 amino acids with 

polyethylene glycol (PEG) reagent (MW 20 kDa). The therapeutic activity of rurioctocog alfa pegol is 

derived from octocog alfa, which is produced by recombinant DNA technology from a Chinese 

hamster ovary cell line. Octocog alfa is then covalently conjugated with the PEG reagent. The PEG 

moiety is conjugated to octocog alfa to increase the plasma half-life.  

 

Clinical efficacy and safety 

The safety, efficacy, and pharmacokinetics of ADYNOVI were evaluated in a pivotal multicenter, 

open-label, prospective clinical trial that compared the efficacy of a twice weekly prophylactic 

treatment regimen to on-demand treatment and determined haemostatic efficacy in the treatment of 

bleeding episodes. A total of 137 male PTPs (12 to 65 years of age) with severe haemophilia A 

received at least one infusion with ADYNOVI. Twenty-five of the 137 subjects were adolescents 

(12 to less than 18 years of age). 

 

Prophylactic treatment 

Subjects received either prophylactic treatment (n = 120) with ADYNOVI at a dose of 40-50 IU 

per kg twice weekly or on-demand treatment (n = 17) with ADYNOVI at a dose of 10-60 IU per kg 

for a 6-month period. The median dosing interval was 3.6 days and the mean dose (SD) 

was 48.7 (4.4) IU/kg. One hundred eighteen of 120 (98%) prophylaxis subjects remained on the 

starting recommended regimen without dose adjustment, and 2 subjects increased their dose 

to 60 IU/kg during prophylaxis due to bleeding in target joints.  

 

In the per-protocol population, i.e. dosed according to the protocol specific dosing requirements, a 

total of 101 subjects received a twice a week regimen in the prophylaxis arm, and 17 subjects were 

treated episodically in the on-demand arm. The median annualised bleed rate (ABR) in the on-demand 

treatment arm was 41.5 compared to 1.9 while on a twice a week prophylaxis regimen. The median 

joint ABR (Q1 ; Q3) in the on-demand arm was 38.1 (24.5 ; 44.6) compared to 0.0 (0.0 ; 2.0) while on 

prophylaxis, and the median spontaneous ABR was 21.6 (11.2 ; 33.2) on the on-demand arm 

compared to 0.0 (0.0 ; 2.2) while on prophylaxis. Results for the full-analysis population were similar 

to those for the per-protocol population. Of note, ABR is not comparable between different factor 

concentrates and between different clinical studies. 

 

Forty out of 101 subjects (40%) experienced no bleeding episodes, 58 out of 101 subjects (57%) 

experienced no joint bleeding episodes, and 58 out of 101 subjects (57%) experienced no spontaneous 

bleeding episodes in the prophylaxis arm. All subjects in the on-demand arm experienced a bleeding 

episode, including a joint or spontaneous bleeding episode. 

 

Treatment of bleeding episodes 

A total of 518 bleeding episodes were treated with ADYNOVI in the per-protocol population. Of 

these, 361 bleeding episodes (n=17 subjects) occurred in the on-demand arm and 157 (n=61 subjects) 

occurred in the prophylaxis arm. The median dose per infusion to treat all bleeding episodes in the 

per-protocol population was 32.0 (Interquartile Range (IQR): 21.5) IU per kg. Overall, 95.9% of 

bleeding episodes were controlled with 1 to 2 infusions and 85.5% were controlled with 

only 1 infusion. Of the 518 bleeding episodes, 96.1% were rated excellent (full relief of pain and 

cessation of objective signs of bleeding after a single infusion) or good (definite pain relief and/or 

improvement in signs of bleeding after a single infusion) in their response to treatment with 

ADYNOVI. 

 

Paediatric population < 12 years of age 

A total of 66 PTPs with severe haemophilia A were dosed (32 subjects aged < 6 years and 34 subjects 

aged 6 to < 12 years) in the paediatric study. The prophylactic regimen was 40 to 60 IU/kg of 

ADYNOVI twice a week. The mean dose (SD) was 54.3 (6.3) IU/kg and the median frequency of 

infusions per week was 1.87. The median overall ABR was 2.0 (IQR: 3.9) for the 65 subjects in the 

per-protocol population and the median ABRs for spontaneous and joint bleeding episodes were 

both 0 (IQR: 1.9). Twenty four out of 65 subjects (37%) experienced no bleeding episodes, 47 out 



 

22 

of 65 subjects (72%) experienced no joint bleeding episodes, and 43 out of 65 subjects (66%) 

experienced no spontaneous bleeding episodes on prophylaxis. 

 

Of the 70 bleeding episodes observed during the paediatric study, 82.9% were controlled 

with 1 infusion and 91.4% were controlled with 1 or 2 infusions. Control of bleeding was rated 

excellent (full relief of pain and cessation of objective signs of bleeding after a single infusion) or 

good (definite pain relief and/or improvement in signs of bleeding after a single infusion) in 63 out 

of 70 (90.0%) bleeding episodes.  

 

Perioperative management (surgical prophylaxis) 

A total of 21 major surgical procedures and 5 additional minor surgeries were performed and assessed 

in 21 unique subjects in the surgery study. For major surgeries, the preoperative loading dose ranged 

from 36 IU/kg to 109 IU/kg (median: 63 IU/kg); and postoperative total dose ranged from 186 IU/kg 

to 1320 IU/kg (median: 490 IU/kg). The median total dose for major surgeries was 553 IU/kg 

(range: 248-1394 IU/kg) and the median total dose of minor surgeries was 106 IU/kg (range: 76-

132 IU/kg). 

 

Perioperative haemostatic efficacy was rated as excellent (blood loss less than or equal to that 

expected for the same type of procedure performed in a non-haemophilic patient, and required blood 

components for transfusions less than or similar to that expected in non-haemophilic population) for 

all 26 (21 major, 5 minor) procedures. The median (IQR) observed intraoperative blood loss (n = 14) 

was 10.0 (20.0) ml compared to the predicted average blood loss (n = 14) of 150.0 (140.0) ml for 

major orthopaedic surgeries. 

 

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

ADYNOVI in one or more subsets of the paediatric population in the treatment of congenital 

factor VIII deficiency. See 4.2 for information on paediatric use. 

 

5.2 Pharmacokinetic properties 

 

The pharmacokinetics (PK) of ADYNOVI were evaluated in a crossover study with octocog alfa 

in 26 subjects (18 adults and 8 adolescents) and in 22 subjects (16 adults and 6 adolescents) 

after 6 months of treatment with ADYNOVI. Plasma factor VIII activity was measured by the 

one stage clotting assay and chromogenic assay. 

 

ADYNOVI has an extended half-life of 1.4 to 1.5-fold compared to recombinant human coagulation 

factor VIII (octocog alfa) in the adolescent and adult population, as determined based on one stage 

clotting and chromogenic assays, respectively. An increase in AUC and a decrease in clearance as 

compared to the parent molecule, octocog alfa, were also observed. Incremental recovery was 

comparable with both products. The change in PK parameters was similar in both the adult and 

adolescent populations and between one-stage clotting and chromogenic substrate assays. 

 

Paediatric Pharmacokinetics 

Pharmacokinetic parameters calculated from 39 subjects less than 18 years of age (intent-to-treat 

analysis) are available for 14 children (2 to less than 6 years), 17 older children (6 to less 

than 12 years) and 8 adolescent subjects (12 to < 18 years of age). The half-life extension in the 

paediatric population was 1.3 to 1.5 fold using both the one stage clotting and chromogenic assays. 

The mean clearance (based on body weight) of ADYNOVI was higher and the mean half-life was 

lower in children less than 12 years of age than adults.  

A higher dose may be required in children less than 12 years of age, see section 4.2.  

 



 

23 

Table 3: Pharmacokinetic parameters using the chromogenic assay 

(Arithmetic mean ± SD) 

PK parameters 

ADYNOVI 

Adults 

(18 years and 

older) 

N = 18 

Dose:  

45 ± 5 IU/kg 

ADYNOVI 

Adolescents 

(12-<18 years) 

N = 8 

Dose:  

45 ± 5 IU/kg 

ADYNOVI 

Paediatric 

patients 

(6-<12 years) 

N = 17 

Dose:  

50 ± 10 IU/kg 

ADYNOVI 

Paediatric 

patients 

(< 6 years) 

N = 14 

Dose:  

50 ± 10 IU/kg 

Design Individual PK with full samplinga Population PK with sparse sampling
b 

Terminal 

half--life [h] 
15.01 ± 3.89 

13.80 ± 4.01 11.93 ± 2.58 12.99 ± 8.75 

MRT [h] 19.70 ± 5.05 17.73 ± 5.44 17.24 ± 3.73 18.74 ± 12.60 

CL [mL/(kg·h)]d 2.16 ± 0.75 2.58 ± 0.84 2.80 ± 0.67 3.49 ± 1.21 

Incremental 

recovery 

[(IU/dL)/(IU/kg)] 

2.87 ± 0.61 2.34 ± 0.62 nac 

(2.19± 0.40) 

nac 

(1.90 ± 0.27) 

AUC0-Inf 

[IU·h/dL] 

2589 ± 848 1900 ± 841 2259 ± 514 2190 ± 1593 

Vss [dL/kg] 0.40 ± 0.09 0.54 ± 0.22 0.46 ± 0.04 0.54 ± 0.03 

Cmax [IU/dL] 
145 ± 29 117 ± 28 nac 

(130 ± 24) 

nac 

(117 ± 16) 

Abbreviations: Cmax: maximum observed activity; AUC: area under the curve; MRT: mean residence 

time; CL: clearance; Vss: body weight adjusted volume of distribution at steady-state,  
a Individual PK with 12 post-infusion samples. 
b Population PK model with 3 post-infusion samples based on randomized drawing schedule. 
c NA, Not applicable, as Incremental Recovery and Cmax in children were determined by individual 

PK. Results for Incremental Recovery and Cmax determined by individual PK in parenthesis. 
d The clearance value of 12.18 ml/(kg·h) for subject 122001 in age group 12 to < 18 years was not 

included in the analysis of clearance. 

 

5.3 Preclinical safety data 

 

In the repeat dose toxicity study in Cynomologous monkey, two animals showed vacuolation in the 

kidney in the mid dose group (350IU/kg). The vacuolations did not recover after 2 weeks. The human 

relevance of kidney vacuolation observed in the preclinical study is unknown. 

 

Nonclinical data are limited to 1 month exposure and no studies in juvenile animals were conducted 

with ADYNOVI. Thus it was not possible to conclude on the potential risks of PEG accumulation in 

various tissues/organs relevant for chronic use of ADYNOVI in the paediatric population No studies 

on genotoxicity, carcinogenicity or reproductive toxicity have been performed with ADYNOVI. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Powder 

Mannitol  

Trehalose dihydrate  

Histidine  

Glutathione  

Sodium chloride  

Calcium chloride dihydrate 

Tris(hydroxymethyl)aminomethane  

Polysorbate 80  



 

24 

 

Solvent 

Sterilised water for injections 

 

6.2 Incompatibilities 

 

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 

products.  

 

6.3 Shelf life 

 

Unopened vial 

2 years.  

 

Before opening the product may be stored at room temperature (up to 30° C) for a period of up 

to 3 months. The end of the 3-month storage at room temperature should be recorded on the product 

carton. This date should never exceed the one initially mentioned on the outer carton. At the end of 

this period the product shall not be put back in the refrigerator, but shall be used or discarded. 

 

After reconstitution 

Chemical and physical in-use stability has been demonstrated for 3 hours at a temperature not 

above 30° C. From a microbiological point of view, unless the method of reconstitution precludes the 

risk of microbial contamination, the product should be used immediately. If not used immediately, 

in-use storage times and conditions are the responsibility of the user. Do not refrigerate. 

 

6.4 Special precautions for storage 

 

Store refrigerated (2°to 8° C). 

Do not freeze. 

ADYNOVI with BAXJECT II Hi-Flow device: Keep the vial in the outer carton in order to protect 

from light. 

ADYNOVI in BAXJECT III system: Keep the sealed blister in the outer carton in order to protect 

from light. 

 

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

 

6.5 Nature and contents of container  

 

Type I glass vial, closed with a chlorobutyl rubber stopper, containing 250 IU, 500 IU, or 1000 IU of 

powder. 

Type I glass vial, closed with a chlorobutyl rubber stopper, containing 2 ml of sterilised water for 

injections. 

The medicinal product is provided in one of the following configurations: 

 

- ADYNOVI with BAXJECT II Hi-Flow device: Each pack contains a powder vial, a solvent vial 
and a device for reconstitution (BAXJECT II Hi-Flow). 

- ADYNOVI in BAXJECT III system: Each pack contains a ready to use BAXJECT III system in 
a sealed blister, withthe powder vial and the solvent vial preassembled for reconstitution. 

 

6.6 Special precautions for disposal and other handling 

 

The reconstituted medicinal product should be inspected visually for particulate matter and 

discoloration prior to administration. The solution should be clear or slightly opalescent. Solutions that 

are cloudy or have deposits should not be used.  

After reconstitution, the solution has a pH of 6.7 to 7.3. The osmolality is ≥ 380 mOsmol/kg. 

 



 

25 

Preparation and reconstitution using the BAXJECT II Hi-Flow device: 

For reconstitution use only the solvent vial and the reconstitution device provided in the pack. 

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

reconstitution procedure. 

2. Allow the vials of powder and solvent to reach room temperature (between 15 °C and 25 °C) 

before use. 

3. Remove plastic caps from the powder and solvent vials. 

4. Clean rubber stoppers with an alcohol wipe and allow to dry prior to use. 

5. Open the BAXJECT II Hi-Flow device package by peeling away the lid, without touching the 

inside (Figure A). Do not remove the device from the package. 

6. Turn the package over. Press straight down to fully insert the clear plastic spike through the 

solvent vial stopper (Figure B).  

7. Grip the BAXJECT II Hi-Flow package at its edge and pull the package off the device 

(Figure C). Do not remove the blue cap from the BAXJECT II Hi-Flow device. Do not touch 

the exposed purple plastic spike. 

8. Turn the system over so that the solvent vial is on top. Quickly insert the purple plastic spike 

fully into the powder vial stopper by pushing straight down (Figure D). The vacuum will draw 

the solvent into the powder vial. 

9. Swirl gently until the powder is completely dissolved. Do not refrigerate after reconstitution. 

 

Figure A Figure B Figure C 

   
Figure D Figure E Figure F 

   
 

Administration 

• Visually inspect the reconstituted solution for particulate matter and discoloration prior to 
administration.  

o The appearance of the reconstituted solution is clear and colourless.  
o Do not use if particulate matter or discoloration is observed. 

• Administer as soon as possible, but no later than 3 hours after reconstitution.  
 

Administration Steps: 

 

1. Remove the blue cap from the BAXJECT II Hi-Flow device (Figure E). Do not draw air into 

the syringe. Connect the syringe to the BAXJECT II Hi-Flow. Use of a Luer-lock syringe is 

recommended.  



 

26 

2. Turn the system upside down (powder vial now on top). Draw the reconstituted solution into the 

syringe by pulling the plunger back slowly (Figure F).  

3. Disconnect the syringe; attach a suitable needle and inject intravenously. If a patient is to 

receive more than one vial of ADYNOVI, the contents of multiple vials may be drawn into the 

same syringe.  

A separate BAXJECT II Hi-Flow device is required to reconstitute each vial of ADYNOVI with 

the solvent. 

4. Administer over a period of up to 5 minutes (maximum infusion rate 10 ml per min).  

 

It is strongly recommended that every time ADYNOVI is administered, the name and batch number of 

the product are recorded. Peel-off labels are provided on the powder vial. 

 

Reconstitution with the BAXJECT III system 

Do not use if the lid is not completely sealed on the blister 

 

1. If the product is still stored in a refrigerator, take the sealed blister (contains powder and solvent 

vials preassembled with the system for reconstitution) from the refrigerator and let it reach room 

temperature (between 15 °C and 25 °C). 

2. Wash your hands thoroughly using soap and warm water. 

3. Open the ADYNOVI blister by peeling away the lid. Remove the BAXJECT III system from 

the blister. 

4. Place the powder vial on a flat surface with the solvent vial on top (Figure 1). The solvent vial 

has a blue stripe. Do not remove the blue cap until instructed in a later step. 

5. With one hand holding the powder vial in the BAXJECT III system, press down firmly on the 

solvent vial with the other hand until the system is fully collapsed and the solvent flows down 

into the powder vial (Figure 2). Do not tilt the system until the transfer is complete. 

6. Verify that the solvent transfer is complete. Swirl gently until all material is dissolved 

(Figure 3). Be sure that the powder is completely dissolved, otherwise not all reconstituted 

solution will pass through the device filter. The product dissolves rapidly (usually in less 

than 1 minute). After reconstitution the solution should be clear, colourless and free from 

particles. 

 

Figure 1 Figure 2 Figure 3 

   
 

Administration 

• Visually inspect the reconstituted solution for particulate matter and discoloration prior to 
administration.  

o The appearance of the reconstituted solution is clear and colourless.  
o Do not use if particulate matter or discoloration is observed. 

• Administer as soon as possible, but no later than 3 hours after reconstitution.  
 

Administration Steps: 

 

1. Remove the blue cap from the BAXJECT III device. Do not draw air into the syringe. 

Connect the syringe to the BAXJECT III device. Use of a Luer-lock syringe is recommended. 

2. Turn the system upside down (powder vial now on top). Draw the reconstituted solution into the 

syringe by pulling the plunger back slowly.  



 

27 

3. Disconnect the syringe; attach a suitable needle and inject intravenously. If a patient is to 

receive more than one vial of ADYNOVI, the contents of multiple vials may be drawn into the 

same syringe.  

4. Administer over a period of up to 5 minutes (maximum infusion rate 10 ml per min).  

 

It is strongly recommended that every time ADYNOVI is administered, the name and batch number of 

the product are recorded. Peel-off labels are provided on the blister. 

 

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

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH  

Industriestrasse 67  

A-1221 Vienna  

Austria 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/17/1247/001 

EU/1/17/1247/002 

EU/1/17/1247/005 

EU/1/17/1247/006 

EU/1/17/1247/009 

EU/1/17/1247/010 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 08 January 2018 

 

 

10. DATE OF REVISION OF THE TEXT 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

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

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


 

28 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

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

AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 



 

29 

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

MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

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

 

Baxalta US Inc 

1700 Rancho Conejo Boulevard 

Thousand Oaks 

California 

CA-91320 

UNITED STATES 

 

Name and address of the manufacturer(s) responsible for batch release 

 

Baxalta Belgium Manufacturing SA 

Boulevard Rene Branquart 80 

B-7860 Lessines 

BELGIUM 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  

 

Medicinal product subject to restricted medical prescription. (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic Safety Update Reports 
 

The requirements for submission of periodic safety update reports for this medicinal product are set 

out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 

2001/83/EC and any subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT  

 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 

agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 

updates of the RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile 

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

reached. 

 



 

30 

• 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 post-authorisation safety study 

according to an agreed protocol. 

Q1-2029 

 



 

31 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



 

32 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

 



 

33 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT II HI-FLOW DEVICE) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 250 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 250 IU rurioctocog alfa pegol, 50 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial, 1 vial with 5 ml solvent, 1 BAXJECT II Hi-Flow device. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

34 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage: 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/17/1247/003 

 

 

13. BATCH NUMBER  

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 250 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC:  

SN:  

NN: ]> 

 

 



 

35 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT II HI-FLOW DEVICE) 

 

 

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

 

ADYNOVI 250 IU / 5 ml powder for injection 

 

rurioctocog alfa pegol 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use only. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

250 IU  

 

 

6. OTHER 

 

 



 

36 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT II HI-FLOW DEVICE) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 500 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 500 IU rurioctocog alfa pegol, 100 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial, 1 vial with 5 ml solvent, 1 BAXJECT II Hi-Flow device. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

37 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage: 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/17/1247/007 

 

 

13. BATCH NUMBER  

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 500 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC:  

SN:  

NN: ]> 

 

 



 

38 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT II HI-FLOW DEVICE) 

 

 

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

 

ADYNOVI 500 IU / 5 ml powder for injection 

 

rurioctocog alfa pegol 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use only. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

500 IU 

 

 

6. OTHER 

 

 



 

39 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT II HI-FLOW DEVICE) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 1000 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 1000 IU rurioctocog alfa pegol, 200 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial, 1 vial with 5 ml solvent, 1 BAXJECT II Hi-Flow device. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

40 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage: 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/17/1247/011 

 

 

13. BATCH NUMBER  

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 1000 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC:  

SN:  

NN: ]> 

 

 



 

41 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT II HI-FLOW DEVICE) 

 

 

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

 

ADYNOVI 1000 IU / 5 ml powder for injection 

 

rurioctocog alfa pegol 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use only. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1000 IU 

 

 

6. OTHER 

 

 



 

42 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT II HI-FLOW DEVICE) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 2000 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 2000 IU rurioctocog alfa pegol, 400 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial, 1 vial with 5 ml solvent, 1 BAXJECT II Hi-Flow device. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

43 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage: 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/17/1247/013 

 

 

13. BATCH NUMBER  

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 2000 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC:  

SN:  

NN: ]> 

 

 



 

44 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT II HI-FLOW DEVICE) 

 

 

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

 

ADYNOVI 2000 IU / 5 ml powder for injection 

 

rurioctocog alfa pegol 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use only. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

2000 IU 

 

 

6. OTHER 

 

 



 

45 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE SOLVENT (BAXJECT II HI-FLOW DEVICE) 

 

 

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

 

Sterilised water for injections 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

5 ml 

 

 

6. OTHER 

 



 

46 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 250 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 250 IU rurioctocog alfa pegol, 50 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial and 1 vial with 5 ml solvent preassembled in BAXJECT III system. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

47 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage:  

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1247/004 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 250 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC: 

SN: 

NN:> 

 

 



 

48 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 250 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

Intravenous use, after reconstitution. 

Use within 3 hours of reconstitution. 

Do not use if packaging is opened or damaged. 

Powder and solvent vials preassembled in BAXJECT III system. 

 



 

49 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ASSEMBLY LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 250 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

   
 



 

50 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT III SYSTEM) 

 

 

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

 

ADYNOVI 250 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 



 

51 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 500 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 500 IU rurioctocog alfa pegol, 100 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial and 1 vial with 5 ml solvent preassembled in BAXJECT III system. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

52 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage:  

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1247/008 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 500 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC: 

SN: 

NN:> 

 

 



 

53 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 500 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

Intravenous use, after reconstitution. 

Use within 3 hours of reconstitution. 

Do not use if packaging is opened or damaged. 

Powder and solvent vials preassembled in BAXJECT III system. 

 



 

54 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ASSEMBLY LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 500 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

   
 



 

55 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT III SYSTEM) 

 

 

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

 

ADYNOVI 500 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 



 

56 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 1000 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 1000 IU rurioctocog alfa pegol, 200 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial and 1 vial with 5 ml solvent preassembled in BAXJECT III system. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

57 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage:  

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1247/012 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 1000 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC: 

SN: 

NN:> 

 

 



 

58 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 1000 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

Intravenous use, after reconstitution. 

Use within 3 hours of reconstitution. 

Do not use if packaging is opened or damaged. 

Powder and solvent vials preassembled in BAXJECT III system. 

 



 

59 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ASSEMBLY LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 1000 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

   
 



 

60 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT III SYSTEM) 

 

 

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

 

ADYNOVI 1000 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 



 

61 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 2000 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 2000 IU rurioctocog alfa pegol, 400 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial and 1 vial with 5 ml solvent preassembled in BAXJECT III system. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

62 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage:  

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1247/014 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 2000 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC: 

SN: 

NN:> 

 

 



 

63 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 2000 IU / 5 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

Intravenous use, after reconstitution. 

Use within 3 hours of reconstitution. 

Do not use if packaging is opened or damaged. 

Powder and solvent vials preassembled in BAXJECT III system. 

 



 

64 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ASSEMBLY LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 2000 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

   
 



 

65 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT III SYSTEM) 

 

 

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

 

ADYNOVI 2000 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 



 

66 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE SOLVENT (BAXJECT III SYSTEM) 

 

 

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

 

Sterilised water for injections 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 



 

67 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT II HI-FLOW DEVICE) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 250 IU / 2 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 250 IU rurioctocog alfa pegol, 125 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial, 1 vial with 2 ml solvent, 1 BAXJECT II Hi-Flow device. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

68 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage: 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1247/001 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 250 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC: 

SN: 

NN: > 

 

 



 

69 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT II HI-FLOW DEVICE) 

 

 

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

 

ADYNOVI 250 IU / 2 ml powder for injection 

 

rurioctocog alfa pegol 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use only. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

250 IU 

 

 

6. OTHER 

 

 



 

70 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT II HI-FLOW DEVICE) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 500 IU / 2 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 500 IU rurioctocog alfa pegol, 250 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial, 1 vial with 2 ml solvent, 1 BAXJECT II Hi-Flow device. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

71 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage: 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1247/005 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 500 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC: 

SN: 

NN: > 

 

 



 

72 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT II HI-FLOW DEVICE) 

 

 

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

 

ADYNOVI 500 IU / 2 ml powder for injection 

 

rurioctocog alfa pegol 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use only. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

500 IU 

 

 

6. OTHER 

 

 



 

73 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT II HI-FLOW DEVICE) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 1000 IU / 2 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 1000 IU rurioctocog alfa pegol, 500 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial, 1 vial with 2 ml solvent, 1 BAXJECT II Hi-Flow device. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

74 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage: 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1247/009 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 1000 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC: 

SN: 

NN: > 

 

 



 

75 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT II HI-FLOW DEVICE) 

 

 

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

 

ADYNOVI 1000 IU / 2 ml powder for injection 

 

rurioctocog alfa pegol 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use only. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1000 IU 

 

 

6. OTHER 

 

 



 

76 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE SOLVENT (BAXJECT II HI-FLOW DEVICE) 

 

 

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

 

Sterilised 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 ml 

 

 

6. OTHER 

 



 

77 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 250 IU / 2 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 250 IU rurioctocog alfa pegol, 125 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial and 1 vial with 2 ml solvent preassembled in BAXJECT III system. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

78 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage: 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1247/002 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 250 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC: 

SN: 

NN:> 

 

 



 

79 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 250 IU / 2 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

Intravenous use, after reconstitution. 

Use within 3 hours of reconstitution. 

Do not use if packaging is opened or damaged. 

Powder and solvent vials preassembled in BAXJECT III system. 

 



 

80 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ASSEMBLY LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 250 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

   
 



 

81 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT III SYSTEM) 

 

 

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

 

ADYNOVI 250 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 



 

82 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 500 IU / 2 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 500 IU rurioctocog alfa pegol, 250 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial and 1 vial with 2 ml solvent preassembled in BAXJECT III system. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

83 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage: 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1247/006 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 500 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC: 

SN: 

NN:> 

 

 



 

84 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 500 IU / 2 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

Intravenous use, after reconstitution. 

Use within 3 hours of reconstitution. 

Do not use if packaging is opened or damaged. 

Powder and solvent vials preassembled in BAXJECT III system. 

 



 

85 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ASSEMBLY LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 500 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

   
 



 

86 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT III SYSTEM) 

 

 

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

 

ADYNOVI 500 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 



 

87 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 1000 IU / 2 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 1000 IU rurioctocog alfa pegol, 500 IU/ml after reconstitution. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, calcium chloride 

dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

1 powder vial and 1 vial with 2 ml solvent preassembled in BAXJECT III system. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Intravenous use, after reconstitution. 

Single use only. 

Read the package leaflet before use. 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP: 

 

Use within 3 hours of reconstitution. 

 

 



 

88 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator. 

Do not freeze. 

 

End of 3-month room temperature storage: 

 

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

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/17/1247/010 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

ADYNOVI 1000 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

< PC: 

SN: 

NN:> 

 

 



 

89 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

BLISTER LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 1000 IU / 2 ml powder and solvent for solution for injection 

 

rurioctocog alfa pegol 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

Intravenous use, after reconstitution. 

Use within 3 hours of reconstitution. 

Do not use if packaging is opened or damaged. 

Powder and solvent vials preassembled in BAXJECT III system. 

 



 

90 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

ASSEMBLY LABEL (BAXJECT III SYSTEM) 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

ADYNOVI 1000 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. OTHER 

 

   
 



 

91 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER (BAXJECT III SYSTEM) 

 

 

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

 

ADYNOVI 1000 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 

 

 



 

92 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE SOLVENT (BAXJECT III SYSTEM) 

 

 

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

 

Sterilised water for injections 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

 

6. OTHER 



 

93 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 

94 

Package leaflet: Information for the user 

 

ADYNOVI 250 IU / 5 ml powder and solvent for solution for injection 

ADYNOVI 500 IU / 5 ml powder and solvent for solution for injection 

ADYNOVI 1000 IU / 5 ml powder and solvent for solution for injection 

ADYNOVI 2000 IU / 5 ml powder and solvent for solution for injection 

 

Rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

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

safety information. You can help by reporting any side effects you may get. See the end of section 4 

for how to report side effects. 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  

- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 
in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What ADYNOVI is and what it is used for  

2. What you need to know before you use ADYNOVI 

3. How to use ADYNOVI 

4. Possible side effects  

5. How to store ADYNOVI 

6. Contents of the pack and other information 

 

 

1. What ADYNOVI is and what it is used for 

 

ADYNOVI contains the active substance rurioctocog alfa pegol, pegylated human coagulation 

factor VIII. The human coagulation factor VIII has been modified to prolong its duration of action. 

Factor VIII is necessary for the blood to form clots and stop bleedings. In patients with haemophilia A 

(inborn lack of factor VIII), it is missing or not working properly. 

 

ADYNOVI is used for the treatment and prevention of bleeding in patients from 12 years of age with 

haemophilia A (an inherited bleeding disorder caused by lack of factor VIII). 

 

 

2. What you need to know before you use ADYNOVI  

 

Do not use ADYNOVI: 

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

- if you are allergic to mouse or hamster proteins 
 

If you are unsure about this, ask your doctor. 

 

Warnings and precautions  

Talk to your doctor before using ADYNOVI. 

 

There is a rare risk that you may experience an anaphylactic reaction (a severe, sudden allergic 

reaction) to ADYNOVI. You should be aware of the early signs of allergic reactions such as rash, 



 

95 

hives, wheals, generalised itching, swelling of lips and tongue, difficulty in breathing, wheezing, 

tightness in the chest, general feeling of being unwell, and dizziness. These could be early symptoms 

of anaphylactic shock; additional symptoms may include extreme dizziness, loss of consciousness, and 

extreme difficulty in breathing. 

If any of these symptoms occur, stop the injection immediately and contact your doctor. Severe 

symptoms, including difficulty in breathing and (near) fainting, require prompt emergency treatment. 

 

If you suffer from cardiac disease, please inform your doctor, as there is an increased risk of blood 

clotting (coagulation) complications. 

 

Patients developing factor VIII inhibitors 

The formation of inhibitors (antibodies) is a known complication that can occur during treatment with 

all Factor VIII medicines. These inhibitors, especially at high levels, stop the treatment working 

properly and you or your child will be monitored carefully for the development of these inhibitors. If 

you or your child´s bleeding is not being controlled with ADYNOVI, tell your doctor immediately. 

 

Catheter-related complications  

If you require a central venous access device (CVAD), risk of CVAD-related complications including 

local infections, presence of bacteria in the blood and catheter site thrombosis should be considered. 

 

Children and adolescents 

ADYNOVI can be used only in adolescents and adults (12 years and above). The listed warnings and 

precautions also apply to adolescents. 

 

Other medicines and ADYNOVI 

Tell your doctor if you are using, have recently used or might use any other medicines. 

 

Pregnancy and breast-feeding  

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before using this medicine. Haemophilia A occurs only rarely in women. 

Therefore no experience regarding the use of ADYNOVI during preganancy and breast-feeding is 

available. 

 

Driving and using machines 

ADYNOVI has no influence on your ability to drive or to use machines. 

 

ADYNOVI contains sodium 

This medicine contains 0.45 mmol sodium (10 mg) per vial. This should be taken into consideration 

by patients on a controlled sodium diet. 

 

 

3. How to use ADYNOVI 

 

Treatment with ADYNOVI will be started and supervised by a doctor who is experienced in the care 

of patients with haemophilia A. 

 

Your doctor will calculate your dose of ADYNOVI depending on your condition and body weight, 

and on whether it is used for prevention or treatment of bleeding. The frequency of administration will 

depend on how well ADYNOVI is working for you. Usually, the replacement therapy with 

ADYNOVI is a life-long treatment. 

 

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

sure. 

 

Prevention of bleeding 

The usual dose of ADYNOVI is 40 to 50 IU per kg body weight, administered 2 times per week. 

 



 

96 

Treatment of bleeding 

The dose of ADYNOVI is calculated depending on your body weight and the factor VIII levels to be 

achieved. The target factor VIII levels will depend on the severity and location of the bleeding. 

If you think that the effect of ADYNOVI is insufficient, talk to your doctor. 

Your doctor will perform appropriate laboratory tests to make sure that you have adequate factor VIII 

levels. This is particularly important if you are having major surgery. 

 

Use in children and adolescents 

ADYNOVI can be used only in adolescents and adults (12 years and above). The dose in adolescents 

is also calculated to body weight and is the same dose as for adults. 

 

How ADYNOVI is given 

ADYNOVI is usually injected into a vein (intravenously) by your doctor or nurse. You or someone 

else might also administer ADYNOVI as an injection, but only after receiving adequate training. 

Detailed instructions for self-administration are given at the end of this package leaflet. 

 

If you use more ADYNOVI than you should 

Always use ADYNOVI exactly as your doctor has told you. You should check with your doctor if you 

are not sure. If you inject more ADYNOVI than recommended, tell your doctor as soon as possible. 

 

If you forget to use ADYNOVI 

Do not inject a double dose to make up for a forgotten dose. Proceed with the next injection as 

scheduled and continue as advised by your doctor. 

 

If you stop using ADYNOVI 

Do not stop using ADYNOVI without consulting your doctor. 

 

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

 

 

4. Possible side effects 

 

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

 

If severe, sudden allergic reactions (anaphylactic) occur, the injection must be stopped 

immediately. You must contact your doctor immediately if you have any of the following early 

symptoms of allergic reactions: 

 

- rash, hives, wheals, generalised itching, 
- swelling of lips and tongue, 
- difficulty in breathing, wheezing, tightness in the chest, 
- general feeling of being unwell, 
- dizziness and loss of consciousness. 
 

Severe symptoms, including difficulty in breathing and (nearly) fainting, require prompt emergency 

treatment. 

 

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. 

 

Common side effects (may affect up to 1 in 10 people) 

Headache, nausea, diarrhoea, rash 

 

Uncommon side effects (may affect up to 1 in 100 people) 

Flushing, allergic reaction (hypersensitivity) 



 

97 

Factor VIII inhibitors (for patients who have received previous treatment with Factor VIII (more than 

150 days of treatment)) 

 

Additional side effects in children 

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. 

 

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 ADYNOVI 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date, which is stated on the label and carton after EXP. The 

expiry date refers to the last day of that month. 

 

Store in a refrigerator (2 °C – 8 °C). 

Do not freeze. 

Keep the vial in the outer carton in order to protect from light. 

 

During the shelf life the powder vial may be kept at room temperature (up to 30 °C) for a single period 

not exceeding 3 months. In this case, this medicine expires at the end of this 3-month period or the 

expiration date printed on the product vial, whichever is earlier. Please record the end of the 3-month 

storage at room temperature on the product carton. The product may not be returned to refrigerated 

storage after storage at room temperature. Do not refrigerate the solution after preparation. 

 

Use the product within 3 hours once the powder is completely dissolved. 

 

The product is for single use only. Discard any unused solution appropriately. 

 

Do not throw away any medicines via waste water or household waste. Ask your pharmacist how to 

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

 

 

6. Contents of the pack and other information 

 

What ADYNOVI contains 

- The active substance is rurioctocog alfa pegol (pegylated human coagulation factor VIII 
produced by recombinant DNA technology). Each powder vial contains 

nominally 250, 500, 1000, or 2000 IU rurioctocog alfa pegol. 

- The solvent vial contains 5 ml of sterilised water for injections. 
 

- The other ingredients are mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, 
calcium chloride dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 and sterilised 

water for injections. ADYNOVI contains sodium, see section 2. 

 

What ADYNOVI looks like and contents of the pack 

ADYNOVI is provided as a powder and solvent for solution for injection. The powder is a white to 

off-white crumbly powder. The solvent is a clear, colourless solution. After reconstitution, the solution 

is clear, colourless and free from foreign particles. 

 

Each pack contains one powder vial, one solvent vial and a device for reconstitution 

(BAXJECT II Hi-Flow). 

 

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


 

98 

Marketing Authorisation Holder 

Baxalta Innovations GmbH 

Industriestrasse 67 

A-1221 Vienna 

Tel: +44(0)1256 894 959 

e-mail: medinfoEMEA@shire.com 

 

Manufacturer 

Baxalta Belgium Manufacturing SA 

Boulevard René Branquart 80 

B-7860 Lessines 

Belgium 

 

This leaflet was last revised in 

 

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

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

 

 

Instructions for preparation and administration 

 

Use only the solvent and the reconstitution device for preparation of the solution that are provided 

with each package of ADYNOVI. The powder must not be mixed with other medicinal products or 

solvents or used with other reconstitution devices. 

 

It is strongly recommended that every time ADYNOVI is administered, the name and batch number of 

the product are recorded. Peel-off labels are provided on the powder vial. 

 

Instructions for reconstitution 

• Do not use after the expiry date stated on the labels and carton. 

• Do not use if the BAXJECT II Hi-Flow device, its sterile barrier system or its packaging is 
damaged or shows any sign of deterioration. 

 

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

reconstitution procedure. 

2. Allow the vials of powder and solvent to reach room temperature (between 15 °C and 25 °C) 

before use. 

3. Remove plastic caps from the powder and solvent vials. 

4. Clean rubber stoppers with an alcohol wipe and allow to dry prior to use. 

5. Open the BAXJECT II Hi-Flow device package by peeling away the lid, without touching the 

inside (Figure A). Do not remove the device from the package. 

6. Turn the package over. Press straight down to fully insert the clear plastic spike through the 

solvent vial stopper (Figure B).  

7. Grip the BAXJECT II Hi-Flow package at its edge and pull the package off the device 

(Figure C). Do not remove the blue cap from the BAXJECT II Hi-Flow device. Do not touch 

the exposed purple plastic spike. 

8. Turn the system over so that the solvent vial is on top. Quickly insert the purple plastic spike 

fully into the powder vial stopper by pushing straight down (Figure D). The vacuum will draw 

the solvent into the powder vial. 

9. Swirl gently until the powder is completely dissolved. Do not refrigerate after reconstitution. 

 

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


 

99 

Figure A Figure B Figure C 

   
 

Figure D Figure E Figure F 

   
 

Instructions for injection 

 

Important note: 

• Inspect the prepared solution for particulate matter and discoloration prior to administration (the 
solution should be clear, colourless and free from particles). 

Do not use ADYNOVI if the solution is not fully clear or not completely dissolved. 

 

1. Remove the blue cap from the BAXJECT II Hi-Flow device (Figure E). Do not draw air into 

the syringe. Connect the syringe to the BAXJECT II Hi-Flow device. Use of a Luer-lock 

syringe is recommended. 

2. Turn the system upside down (powder vial now on top). Draw the reconstituted solution into the 

syringe by pulling the plunger back slowly (Figure F).  

3. Disconnect the syringe; attach a suitable needle and inject intravenously. If a patient is to 

receive more than one vial of ADYNOVI, the contents of multiple vials may be drawn into the 

same syringe.  

A separate BAXJECT II Hi-Flow device is required to reconstitute each vial of ADYNOVI with 

the solvent. 

4. Administer over a period of up to 5 minutes (maximum infusion rate 10 ml per min).  

5. Discard any unused solution appropriately. 

 

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

 

The following information is intended for healthcare professionals only: 

 

On demand treatment 

In case of the following haemorrhagic events, factor VIII activity should not fall below the given 

plasma activity level (in % of normal or IU/dl) in the corresponding period. The following table can be 

used to guide dosing in bleeding episodes and surgery. 

 



 

100 

Table 1 Guide for dosing in bleeding episodes and surgery 

Degree of haemorrhage/type 

of surgical procedure 

Factor VIII level 

required (% or IU/dl) 

Frequency of doses (hours)/duration 

of therapy (days) 

Haemorrhage   

Early haemarthrosis, muscle 

bleeding or oral bleeding. 

20 – 40 Repeat injections every 12 to 24 hours. 

At least 1 day, until the bleeding 

episode, as indicated by pain, is 

resolved or healing is achieved. 

 

More extensive haemarthrosis, 

muscle bleeding or haematoma 

30 – 60 Repeat injections every 12 to 24 hours 

for 3 – 4 days or more until pain and 

acute disability are resolved. 

 

Life threatening haemorrhages. 60 – 100 Repeat injections every 8 to 24 hours 

until threat is resolved. 

Surgery   

Minor 

Including tooth extraction. 

30 – 60 Every 24 hours at least 1 day, until 

healing is achieved. 

 

Major 80 – 100 

 

(pre- and postoperative) 

Repeat injections every 8 to 24 hours 

until adequate wound healing, then 

continue therapy for at least 

another 7 days to maintain a factor VIII 

activity of 30% to 60% (IU/dl). 

 

Prophylaxis  

 

For long term prophylaxis, the recommended dose is 40 to 50 IU of ADYNOVI per kg bodyweight 

twice weekly in 3 to 4 day intervals. Adjustments of doses and administration intervals may be 

considered based on achieved FVIII levels and individual bleeding tendency (see section 5.2). 

 

Paediatric population  

 

On demand treatment dosing in paediatric patients (12 to 18 years of age) is the same as for adult 

patients. Prophylactic treatment for patients from 12 to <18 years is the same as for adult patients. The 

long-term safety of ADYNOVI in children below 12 years has not yet been established. Adjustments 

of doses and administration intervals may be considered based on achieved FVIII levels and individual 

bleeding tendency (see section 5.2).  



 

101 

Package leaflet: Information for the user 

 

ADYNOVI 250 IU / 5 ml powder and solvent for solution for injection 

ADYNOVI 500 IU / 5 ml powder and solvent for solution for injection 

ADYNOVI 1000 IU / 5 ml powder and solvent for solution for injection 

ADYNOVI 2000 IU / 5 ml powder and solvent for solution for injection 

 

Rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

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

safety information. You can help by reporting any side effects you may get. See the end of section 4 

for how to report side effects. 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  

- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 
in this leaflet. See section 4. 

 

 

What is in this leaflet 

 

1. What ADYNOVI is and what it is used for  

2. What you need to know before you use ADYNOVI 

3. How to use ADYNOVI 

4. Possible side effects  

5. How to store ADYNOVI 

6. Contents of the pack and other information 

 

 

1. What ADYNOVI is and what it is used for 

 

ADYNOVI contains the active substance rurioctocog alfa pegol, pegylated human coagulation 

factor VIII. The human coagulation factor VIII has been modified to prolong its duration of action. 

Factor VIII is necessary for the blood to form clots and stop bleedings. In patients with haemophilia A 

(inborn lack of factor VIII), it is missing or not working properly. 

 

ADYNOVI is used for the treatment and prevention of bleeding in patients from 12 years of age with 

haemophilia A (an inherited bleeding disorder caused by lack of factor VIII). 

 

 

2. What you need to know before you use ADYNOVI  

 

Do not use ADYNOVI: 

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

- if you are allergic to mouse or hamster proteins 
 

If you are unsure about this, ask your doctor. 

 

Warnings and precautions  

Talk to your doctor before using ADYNOVI. 

 



 

102 

There is a rare risk that you may experience an anaphylactic reaction (a severe, sudden allergic 

reaction) to ADYNOVI. You should be aware of the early signs of allergic reactions such as rash, 

hives, wheals, generalised itching, swelling of lips and tongue, difficulty in breathing, wheezing, 

tightness in the chest, general feeling of being unwell, and dizziness. These could be early symptoms 

of anaphylactic shock; additional symptoms may include extreme dizziness, loss of consciousness, and 

extreme difficulty in breathing. 

If any of these symptoms occur, stop the injection immediately and contact your doctor. Severe 

symptoms, including difficulty in breathing and (near) fainting, require prompt emergency treatment. 

 

If you suffer from cardiac disease, please inform your doctor, as there is an increased risk of blood 

clotting (coagulation) complications. 

 

Patients developing factor VIII inhibitors 

The formation of inhibitors (antibodies) is a known complication that can occur during treatment with 

all Factor VIII medicines. These inhibitors, especially at high levels, stop the treatment working 

properly and you or your child will be monitored carefully for the development of these inhibitors. If 

you or your child´s bleeding is not being controlled with ADYNOVI, tell your doctor immediately. 

 

Catheter-related complications  

If you require a central venous access device (CVAD), risk of CVAD-related complications including 

local infections, presence of bacteria in the blood and catheter site thrombosis should be considered. 

 

Children and adolescents 

ADYNOVI can be used only in adolescents and adults (12 years and above). The listed warnings and 

precautions also apply to adolescents. 

 

Other medicines and ADYNOVI 

Tell your doctor if you are using, have recently used or might use any other medicines. 

 

Pregnancy and breast-feeding  

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before using this medicine. Haemophilia A occurs only rarely in women. 

Therefore no experience regarding the use of ADYNOVI during preganancy and breast-feeding is 

available. 

 

Driving and using machines 

ADYNOVI has no influence on your ability to drive or to use machines. 

 

ADYNOVI contains sodium 

This medicine contains 0.45 mmol sodium (10 mg) per vial. This should be taken into consideration 

by patients on a controlled sodium diet. 

 

 

3. How to use ADYNOVI 

 

Treatment with ADYNOVI will be started and supervised by a doctor who is experienced in the care 

of patients with haemophilia A. 

 

Your doctor will calculate your dose of ADYNOVI depending on your condition and body weight, 

and on whether it is used for prevention or treatment of bleeding. The frequency of administration will 

depend on how well ADYNOVI is working for you. Usually, the replacement therapy with 

ADYNOVI is a life-long treatment. 

 

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

sure. 

 



 

103 

Prevention of bleeding 

The usual dose of ADYNOVI is 40 to 50 IU per kg body weight, administered 2 times per week. 

 

Treatment of bleeding 

The dose of ADYNOVI is calculated depending on your body weight and the factor VIII levels to be 

achieved. The target factor VIII levels will depend on the severity and location of the bleeding. 

If you think that the effect of ADYNOVI is insufficient, talk to your doctor. 

Your doctor will perform appropriate laboratory tests to make sure that you have adequate factor VIII 

levels. This is particularly important if you are having major surgery. 

 

Use in children and adolescents 

ADYNOVI can be used only in adolescents and adults (12 years and above). The dose in adolescents 

is also calculated to body weight and is the same dose as for adults. 

 

How ADYNOVI is given 

ADYNOVI is usually injected into a vein (intravenously) by your doctor or nurse. You or someone 

else might also administer ADYNOVI as an injection, but only after receiving adequate training. 

Detailed instructions for self-administration are given at the end of this package leaflet. 

 

If you use more ADYNOVI than you should 

Always use ADYNOVI exactly as your doctor has told you. You should check with your doctor if you 

are not sure. If you inject more ADYNOVI than recommended, tell your doctor as soon as possible. 

 

If you forget to use ADYNOVI 

Do not inject a double dose to make up for a forgotten dose. Proceed with the next injection as 

scheduled and continue as advised by your doctor. 

 

If you stop using ADYNOVI 

Do not stop using ADYNOVI without consulting your doctor. 

 

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

 

 

4. Possible side effects 

 

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

 

If severe, sudden allergic reactions (anaphylactic) occur, the injection must be stopped 

immediately. You must contact your doctor immediately if you have any of the following early 

symptoms of allergic reactions: 

 

- rash, hives, wheals, generalised itching, 
- swelling of lips and tongue, 
- difficulty in breathing, wheezing, tightness in the chest, 
- general feeling of being unwell, 
- dizziness and loss of consciousness. 
 

Severe symptoms, including difficulty in breathing and (nearly) fainting, require prompt emergency 

treatment. 

 

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. 

 

Common side effects (may affect up to 1 in 10 people) 

Headache, nausea, diarrhoea, rash 



 

104 

Uncommon side effects (may affect up to 1 in 100 people) 

Flushing, allergic reaction (hypersensitivity) 

Factor VIII inhibitors (for patients who have received previous treatment with Factor VIII (more than 

150 days of treatment)) 

 

Additional side effects in children 

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. 

 

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 ADYNOVI 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date, which is stated on the label and carton after EXP. The 

expiry date refers to the last day of that month. 

 

Store in a refrigerator (2 °C – 8 °C). 

Do not freeze. 

Keep the blister in the outer carton in order to protect from light. 

 

During the shelf life the powder vial may be kept at room temperature (up to 30 °C) for a single period 

not exceeding 3 months. In this case, this medicine expires at the end of this 3-month period or the 

expiration date printed on the product vial, whichever is earlier. Please record the end of the 3-month 

storage at room temperature on the product carton. The product may not be returned to refrigerated 

storage after storage at room temperature. Do not refrigerate the solution after preparation. 

 

Use the product within 3 hours once the powder is completely dissolved. 

 

The product is for single use only. Discard any unused solution appropriately. 

 

Do not throw away any medicines via waste water or household waste. Ask your pharmacist how to 

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

 

 

6. Contents of the pack and other information 

 

What ADYNOVI contains 

- The active substance is rurioctocog alfa pegol (pegylated human coagulation factor VIII 
produced by recombinant DNA technology). Each powder vial contains 

nominally 250, 500, 1000, or 2000 IU rurioctocog alfa pegol. 

- The solvent vial contains 5 ml of sterilised water for injections. 
 

- The other ingredients are mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, 
calcium chloride dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 and sterilised 

water for injections. ADYNOVI contains sodium, see section 2. 

 

What ADYNOVI looks like and contents of the pack 

ADYNOVI is provided as a powder and solvent for solution for injection. The powder is a white to 

off-white crumbly powder. The solvent is a clear, colourless solution. After reconstitution, the solution 

is clear, colourless and free from foreign particles. 

 

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


 

105 

Marketing Authorisation Holder 

Baxalta Innovations GmbH 

Industriestrasse 67 

A-1221 Vienna 

Tel: +44(0)1256 894 959 

e-mail: medinfoEMEA@shire.com 

 

Manufacturer 

Baxalta Belgium Manufacturing SA 

Boulevard René Branquart 80 

B-7860 Lessines 

Belgium 

 

This leaflet was last revised in 

 

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

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

 

 

Instructions for preparation and administration 

 

ADYNOVI must not be mixed with other medicinal products or solvents. 

 

It is strongly recommended that every time ADYNOVI is administered, the name and batch number of 

the product are recorded. Peel-off labels are provided on the blister. 

 

Instructions for reconstitution 

• Do not use after the expiry date stated on the labels and carton. 

• Do not use if the lid is not completely sealed on the blister 

• Do not refrigerate the solution after preparation. 
 

1. If the product is still stored in a refrigerator, take the sealed blister (contains powder and solvent 

vials preassembled with the system for reconstitution) from the refrigerator and let it reach room 

temperature (between 15 °C and 25 °C). 

2. Wash your hands thoroughly using soap and warm water. 

3. Open the ADYNOVI blister by peeling away the lid. Remove the BAXJECT III system from 

the blister. 

4. Place the powder vial on a flat surface with the solvent vial on top (Figure 1). The solvent vial 

has a blue stripe. Do not remove the blue cap until instructed in a later step. 

5. With one hand holding the powder vial in the BAXJECT III system, press down firmly on the 

solvent vial with the other hand until the system is fully collapsed and the solvent flows down 

into the powder vial (Figure 2). Do not tilt the system until the transfer is complete. 

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


 

106 

6. Verify that the solvent transfer is complete. Swirl gently until all material is dissolved 

(Figure 3). Be sure that the powder is completely dissolved, otherwise not all reconstituted 

solution will pass through the device filter. The product dissolves rapidly (usually in less 

than 1 minute). After reconstitution the solution should be clear, colourless and free from 

foreign particles. 

 

Figure 1 Figure 2 Figure 3 

   
 

Instructions for injection 

Antiseptic technique (clean and low-germ conditions) is required during administration. 

 

Important note: 

• Inspect the prepared solution for particulate matter and discoloration prior to administration (the 
solution should be clear, colourless and free from particles). 

Do not use if the solution is not fully clear or not completely dissolved. 

 

1. Remove the blue cap from BAXJECT III. Do not draw air into the syringe. Connect the 

syringe to BAXJECT III. Use of a Luer-lock syringe is recommended. 

2. Turn the system upside down (powder vial now on top). Draw the reconstituted solution into the 

syringe by pulling the plunger back slowly. 

3. Disconnect the syringe; attach a butterfly needle to the syringe and inject the reconstituted 

solution into a vein. The solution should be administered slowly, at a rate as determined by the 

patient’s comfort level, not to exceed 10 ml per minute. (See section 4 “Possible side effects”). 

4. Discard any unused solution appropriately. 

 

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

 

The following information is intended for healthcare professionals only: 

 

On demand treatment 

In case of the following haemorrhagic events, factor VIII activity should not fall below the given 

plasma activity level (in % of normal or IU/dl) in the corresponding period. The following table can be 

used to guide dosing in bleeding episodes and surgery. 



 

107 

Table 1 Guide for dosing in bleeding episodes and surgery 

Degree of haemorrhage/type 

of surgical procedure 

Factor VIII level 

required (% or IU/dl) 

Frequency of doses (hours)/duration 

of therapy (days) 

Haemorrhage   

Early haemarthrosis, muscle 

bleeding or oral bleeding. 

20 – 40 Repeat injections every 12 to 24 hours. 

At least 1 day, until the bleeding 

episode, as indicated by pain, is 

resolved or healing is achieved. 

 

More extensive haemarthrosis, 

muscle bleeding or haematoma 

30 – 60 Repeat injections every 12 to 24 hours 

for 3 – 4 days or more until pain and 

acute disability are resolved. 

 

Life threatening haemorrhages. 60 – 100 Repeat injections every 8 to 24 hours 

until threat is resolved. 

Surgery   

Minor 

Including tooth extraction. 

30 – 60 Every 24 hours at least 1 day, until 

healing is achieved. 

 

Major 80 – 100 

 

(pre- and postoperative) 

Repeat injections every 8 to 24 hours 

until adequate wound healing, then 

continue therapy for at least 

another 7 days to maintain a factor VIII 

activity of 30% to 60% (IU/dl). 

 

Prophylaxis  

 

For long term prophylaxis, the recommended dose is 40 to 50 IU of ADYNOVI per kg bodyweight 

twice weekly in 3 to 4 day intervals. Adjustments of doses and administration intervals may be 

considered based on achieved FVIII levels and individual bleeding tendency (see section 5.2). 

 

Paediatric population  

 

On demand treatment dosing in paediatric patients (12 to 18 years of age) is the same as for adult 

patients. Prophylactic treatment for patients from 12 to <18 years is the same as for adult patients. The 

long-term safety of ADYNOVI in children below 12 years has not yet been established. Adjustments 

of doses and administration intervals may be considered based on achieved FVIII levels and individual 

bleeding tendency (see section 5.2).  



 

108 

Package leaflet: Information for the user 

 

ADYNOVI 250 IU / 2 ml powder and solvent for solution for injection 

ADYNOVI 500 IU / 2 ml powder and solvent for solution for injection 

ADYNOVI 1000 IU / 2 ml powder and solvent for solution for injection 

 

Rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

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

safety information. You can help by reporting any side effects you may get. See the end of section 4 

for how to report side effects. 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  

- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 
in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What ADYNOVI is and what it is used for  

2. What you need to know before you use ADYNOVI 

3. How to use ADYNOVI 

4. Possible side effects  

5. How to store ADYNOVI 

6. Contents of the pack and other information 

 

 

1. What ADYNOVI is and what it is used for 

 

ADYNOVI contains the active substance rurioctocog alfa pegol, pegylated human coagulation 

factor VIII. The human coagulation factor VIII has been modified to prolong its duration of action. 

Factor VIII is necessary for the blood to form clots and stop bleedings. In patients with haemophilia A 

(inborn lack of factor VIII), it is missing or not working properly. 

 

ADYNOVI is used for the treatment and prevention of bleeding in patients from 12 years of age with 

haemophilia A (an inherited bleeding disorder caused by lack of factor VIII). 

 

 

2. What you need to know before you use ADYNOVI 

 

Do not use ADYNOVI: 

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

- if you are allergic to mouse or hamster proteins 
 

If you are unsure about this, ask your doctor. 

 

Warnings and precautions  

Talk to your doctor before using ADYNOVI.  

 

There is a rare risk that you may experience an anaphylactic reaction (a severe, sudden allergic 

reaction) to ADYNOVI. You should be aware of the early signs of allergic reactions such as rash, 

hives, wheals, generalised itching, swelling of lips and tongue, difficulty in breathing, wheezing, 



 

109 

tightness in the chest, general feeling of being unwell, and dizziness. These could be early symptoms 

of anaphylactic shock; additional symptoms may include extreme dizziness, loss of consciousness, and 

extreme difficulty in breathing. 

If any of these symptoms occur, stop the injection immediately and contact your doctor. Severe 

symptoms, including difficulty in breathing and (near) fainting, require prompt emergency treatment. 

 

If you suffer from cardiac disease, please inform your doctor, as there is an increased risk of blood 

clotting (coagulation) complications. 

 

Patients developing factor VIII inhibitors 

The formation of inhibitors (antibodies) is a known complication that can occur during treatment with 

all Factor VIII medicines. These inhibitors, especially at high levels, stop the treatment working 

properly and you or your child will be monitored carefully for the development of these inhibitors. If 

you or your child´s bleeding is not being controlled with ADYNOVI, tell your doctor immediately. 

 

Catheter-related complications  

If you require a central venous access device (CVAD), risk of CVAD-related complications including 

local infections, presence of bacteria in the blood and catheter site thrombosis should be considered. 

 

Children and adolescents 

ADYNOVI can be used only in adolescents and adults (12 years and above). The listed warnings and 

precautions also apply to adolescents. 

 

Other medicines and ADYNOVI 

Tell your doctor if you are using, have recently used or might use any other medicines. 

 

Pregnancy and breast-feeding  

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before using this medicine. Haemophilia A occurs only rarely in women. 

Therefore no experience regarding the use of ADYNOVI during preganancy and breast-feeding is 

available. 

 

Driving and using machines 

ADYNOVI has no influence on your ability to drive or to use machines. 

 

ADYNOVI contains sodium 

This medicine contains 0.45 mmol sodium (10 mg) per vial. This should be taken into consideration 

by patients on a controlled sodium diet. 

 

 

3. How to use ADYNOVI 

 

Treatment with ADYNOVI will be started and supervised by a doctor who is experienced in the care 

of patients with haemophilia A. 

 

Your doctor will calculate your dose of ADYNOVI depending on your condition and body weight, 

and on whether it is used for prevention or treatment of bleeding. The frequency of administration will 

depend on how well ADYNOVI is working for you. Usually, the replacement therapy with 

ADYNOVI is a life-long treatment. 

 

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

sure. 

 

Prevention of bleeding 

The usual dose of ADYNOVI is 40 to 50 IU per kg body weight, administered 2 times per week. 

 



 

110 

Treatment of bleeding 

The dose of ADYNOVI is calculated depending on your body weight and the factor VIII levels to be 

achieved. The target factor VIII levels will depend on the severity and location of the bleeding. 

If you think that the effect of ADYNOVI is insufficient, talk to your doctor. 

Your doctor will perform appropriate laboratory tests to make sure that you have adequate factor VIII 

levels. This is particularly important if you are having major surgery. 

 

Use in children and adolescents 

ADYNOVI can be used only in adolescents and adults (12 years and above). The dose in adolescents 

is also calculated to body weight and is the same dose as for adults. 

 

How ADYNOVI is given 

ADYNOVI is usually injected into a vein (intravenously) by your doctor or nurse. You or someone 

else might also administer ADYNOVI as an injection, but only after receiving adequate training. 

Detailed instructions for self-administration are given at the end of this package leaflet. 

 

If you use more ADYNOVI than you should 

Always use ADYNOVI exactly as your doctor has told you. You should check with your doctor if you 

are not sure. If you inject more ADYNOVI than recommended, tell your doctor as soon as possible. 

 

If you forget to use ADYNOVI 

Do not inject a double dose to make up for a forgotten dose. Proceed with the next injection as 

scheduled and continue as advised by your doctor. 

 

If you stop using ADYNOVI 

Do not stop using ADYNOVI without consulting your doctor. 

 

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

 

 

4. Possible side effects 

 

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

 

If severe, sudden allergic reactions (anaphylactic) occur, the injection must be stopped 

immediately. You must contact your doctor immediately if you have any of the following early 

symptoms of allergic reactions: 

 

- rash, hives, wheals, generalised itching, 
- swelling of lips and tongue, 
- difficulty in breathing, wheezing, tightness in the chest, 
- general feeling of being unwell, 
- dizziness and loss of consciousness. 
 

Severe symptoms, including difficulty in breathing and (nearly) fainting, require prompt emergency 

treatment. 

 

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. 

 

Common side effects (may affect up to 1 in 10 people) 

Headache, nausea, diarrhoea, rash 

 

Uncommon side effects (may affect up to 1 in 100 people) 

Flushing, allergic reaction (hypersensitivity) 



 

111 

Factor VIII inhibitors (for patients who have received previous treatment with Factor VIII (more than 

150 days of treatment)) 

 

Additional side effects in children 

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. 

 

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 ADYNOVI 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date, which is stated on the label and carton after EXP. The 

expiry date refers to the last day of that month. 

 

Store in a refrigerator (2 °C – 8 °C). 

Do not freeze. 

Keep the vial in the outer carton in order to protect from light. 

 

During the shelf life the powder vial may be kept at room temperature (up to 30 °C) for a single period 

not exceeding 3 months. In this case, this medicine expires at the end of this 3-month period or the 

expiration date printed on the product vial, whichever is earlier. Please record the end of the 3-month 

storage at room temperature on the product carton. The product may not be returned to refrigerated 

storage after storage at room temperature. Do not refrigerate the solution after preparation. 

 

Use the product within 3 hours once the powder is completely dissolved. 

 

The product is for single use only. Discard any unused solution appropriately. 

 

Do not throw away any medicines via waste water or household waste. Ask your pharmacist how to 

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

 

 

6. Contents of the pack and other information 

 

What ADYNOVI contains 

- The active substance is rurioctocog alfa pegol (pegylated human coagulation factor VIII 
produced by recombinant DNA technology). Each powder vial contains nominally 250, 500, 

or 1000 IU rurioctocog alfa pegol. 

- The solvent vial contains 2 ml of sterilised water for injections. 
 

- The other ingredients are mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, 
calcium chloride dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80 and sterilised 

water for injections. ADYNOVI contains sodium, see section 2. 

 

 

What ADYNOVI looks like and contents of the pack 

ADYNOVI is provided as a powder and solvent for solution for injection. The powder is a white to 

off-white crumbly powder. The solvent is a clear, colourless solution. After reconstitution, the solution 

is clear, colourless and free from foreign particles. 

 

Each pack contains one powder vial, one solvent vial and a device for reconstitution 

(BAXJECT II Hi-Flow). 

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


 

112 

 

Marketing Authorisation Holder 

Baxalta Innovations GmbH 

Industriestrasse 67 

A-1221 Vienna 

Tel: +44(0)1256 894 959 

e-mail: medinfoEMEA@shire.com 

 

Manufacturer 

Baxalta Belgium Manufacturing SA 

Boulevard René Branquart 80 

B-7860 Lessines 

Belgium 

 

This leaflet was last revised in 

 

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

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

 

 

Instructions for preparation and administration 

 

Use only the solvent and the reconstitution device for preparation of the solution that are provided 

with each package of ADYNOVI. The powder must not be mixed with other medicinal products or 

solvents or used with other reconstitution devices. 

 

It is strongly recommended that every time ADYNOVI is administered, the name and batch number of 

the product are recorded. Peel-off labels are provided on the powder vial. 

 

Instructions for reconstitution 

• Do not use after the expiry date stated on the labels and carton. 

• Do not use if the BAXJECT II Hi-Flow device, its sterile barrier system or its packaging is 
damaged or shows any sign of deterioration. 

 

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

reconstitution procedure. 

2. Allow the vials of powder and solvent to reach room temperature (between 15 °C and 25 °C) 

before use. 

3. Remove plastic caps from the powder and solvent vials. 

4. Clean rubber stoppers with an alcohol wipe and allow to dry prior to use. 

5. Open the BAXJECT II Hi-Flow device package by peeling away the lid, without touching the 

inside (Figure A). Do not remove the device from the package. 

6. Turn the package over. Press straight down to fully insert the clear plastic spike through the 

solvent vial stopper (Figure B).  

7. Grip the BAXJECT II Hi-Flow package at its edge and pull the package off the device 

(Figure C). Do not remove the blue cap from the BAXJECT II Hi-Flow device. Do not touch 

the exposed purple plastic spike. 

8. Turn the system over so that the solvent vial is on top. Quickly insert the purple plastic spike 

fully into the powder vial stopper by pushing straight down (Figure D). The vacuum will draw 

the solvent into the powder vial. 

9. Swirl gently until the powder is completely dissolved. Do not refrigerate after reconstitution. 

 

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


 

113 

Figure A Figure B Figure C 

   
 

Figure D Figure E Figure F 

   
 

Instructions for injection 

 

Important note: 

• Inspect the prepared solution for particulate matter and discoloration prior to administration (the 
solution should be clear, colourless and free from particles). 

Do not use ADYNOVI if the solution is not fully clear or not completely dissolved. 

 

1. Remove the blue cap from the BAXJECT II Hi-Flow device (Figure E). Do not draw air into 

the syringe. Connect the syringe to the BAXJECT II Hi-Flow device. Use of a Luer-lock 

syringe is recommended.  

2. Turn the system upside down (powder vial now on top). Draw the reconstituted solution into the 

syringe by pulling the plunger back slowly (Figure F).  

3. Disconnect the syringe; attach a suitable needle and inject intravenously. If a patient is to 

receive more than one vial of ADYNOVI, the contents of multiple vials may be drawn into the 

same syringe.  

A separate BAXJECT II Hi-Flow device is required to reconstitute each vial of ADYNOVI with 

the solvent. 

4. Administer over a period of up to 5 minutes (maximum infusion rate 10 ml per min).  

5. Discard any unused solution appropriately. 

 

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

 

The following information is intended for healthcare professionals only: 

 

On demand treatment 

In case of the following haemorrhagic events, factor VIII activity should not fall below the given 

plasma activity level (in % of normal or IU/dl) in the corresponding period. The following table can be 

used to guide dosing in bleeding episodes and surgery. 



 

114 

 

Table 1 Guide for dosing in bleeding episodes and surgery 

Degree of haemorrhage/type 

of surgical procedure 

Factor VIII level 

required (% or IU/dl) 

Frequency of doses (hours)/duration 

of therapy (days) 

Haemorrhage   

Early haemarthrosis, muscle 

bleeding or oral bleeding. 

20 – 40 Repeat injections every 12 to 24 hours. 

At least 1 day, until the bleeding 

episode, as indicated by pain, is 

resolved or healing is achieved. 

 

More extensive haemarthrosis, 

muscle bleeding or haematoma 

30 – 60 Repeat injections every 12 to 24 hours 

for 3 – 4 days or more until pain and 

acute disability are resolved. 

 

Life threatening haemorrhages. 60 – 100 Repeat injections every 8 to 24 hours 

until threat is resolved. 

Surgery   

Minor 

Including tooth extraction. 

30 – 60 Every 24 hours at least 1 day, until 

healing is achieved. 

 

Major 80 – 100 

 

(pre- and postoperative) 

Repeat injections every 8 to 24 hours 

until adequate wound healing, then 

continue therapy for at least 

another 7 days to maintain a factor VIII 

activity of 30% to 60% (IU/dl). 

 

Prophylaxis  

 

For long term prophylaxis, the recommended dose is 40 to 50 IU of ADYNOVI per kg bodyweight 

twice weekly in 3 to 4 day intervals. Adjustments of doses and administration intervals may be 

considered based on achieved FVIII levels and individual bleeding tendency (see section 5.2). 

 

Paediatric population  

 

On demand treatment dosing in paediatric patients (12 to 18 years of age) is the same as for adult 

patients. Prophylactic treatment for patients from 12 to <18 years is the same as for adult patients. The 

long-term safety of ADYNOVI in children below 12 years has not yet been established. Adjustments 

of doses and administration intervals may be considered based on achieved FVIII levels and individual 

bleeding tendency (see section 5.2).  



 

115 

Package leaflet: Information for the user 

 

ADYNOVI 250 IU / 2 ml powder and solvent for solution for injection 

ADYNOVI 500 IU / 2 ml powder and solvent for solution for injection 

ADYNOVI 1000 IU / 2 ml powder and solvent for solution for injection 

 

Rurioctocog alfa pegol (pegylated recombinant human coagulation factor VIII) 

 

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

safety information. You can help by reporting any side effects you may get. See the end of section 4 

for how to report side effects. 

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  

- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 
in this leaflet. See section 4. 

 

What is in this leaflet 

 

1. What ADYNOVI is and what it is used for  

2. What you need to know before you use ADYNOVI 

3. How to use ADYNOVI 

4. Possible side effects  

5. How to store ADYNOVI 

6. Contents of the pack and other information 

 

 

1. What ADYNOVI is and what it is used for 

 

ADYNOVI contains the active substance rurioctocog alfa pegol, pegylated human coagulation 

factor VIII. The human coagulation factor VIII has been modified to prolong its duration of action. 

Factor VIII is necessary for the blood to form clots and stop bleedings. In patients with haemophilia A 

(inborn lack of factor VIII), it is missing or not working properly. 

 

ADYNOVI is used for the treatment and prevention of bleeding in patients from 12 years of age with 

haemophilia A (an inherited bleeding disorder caused by lack of factor VIII). 

 

 

2. What you need to know before you use ADYNOVI 

 

Do not use ADYNOVI: 

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

- if you are allergic to mouse or hamster proteins 
 

If you are unsure about this, ask your doctor. 

 

Warnings and precautions  

Talk to your doctor before using ADYNOVI.  

 

There is a rare risk that you may experience an anaphylactic reaction (a severe, sudden allergic 

reaction) to ADYNOVI. You should be aware of the early signs of allergic reactions such as rash, 

hives, wheals, generalised itching, swelling of lips and tongue, difficulty in breathing, wheezing, 



 

116 

tightness in the chest, general feeling of being unwell, and dizziness. These could be early symptoms 

of anaphylactic shock; additional symptoms may include extreme dizziness, loss of consciousness, and 

extreme difficulty in breathing. 

If any of these symptoms occur, stop the injection immediately and contact your doctor. Severe 

symptoms, including difficulty in breathing and (near) fainting, require prompt emergency treatment. 

 

If you suffer from cardiac disease, please inform your doctor, as there is an increased risk of blood 

clotting (coagulation) complications. 

 

Patients developing factor VIII inhibitors 

The formation of inhibitors (antibodies) is a known complication that can occur during treatment with 

all Factor VIII medicines. These inhibitors, especially at high levels, stop the treatment working 

properly and you or your child will be monitored carefully for the development of these inhibitors. If 

you or your child´s bleeding is not being controlled with ADYNOVI, tell your doctor immediately. 

 

Catheter-related complications  

If you require a central venous access device (CVAD), risk of CVAD-related complications including 

local infections, presence of bacteria in the blood and catheter site thrombosis should be considered. 

 

Children and adolescents 

ADYNOVI can be used only in adolescents and adults (12 years and above). The listed warnings and 

precautions also apply to adolescents. 

 

Other medicines and ADYNOVI 

Tell your doctor if you are using, have recently used or might use any other medicines. 

 

Pregnancy and breast-feeding  

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before using this medicine. Haemophila A occurs only rarely in women. 

Therefore no experience regarding the use of ADYNOVI during preganancy and breast-feeding is 

available. 

 

Driving and using machines 

ADYNOVI has no influence on your ability to drive or to use machines. 

 

ADYNOVI contains sodium 

This medicine contains 0.45 mmol sodium (10 mg) per vial. This should be taken into consideration 

by patients on a controlled sodium diet. 

 

 

3. How to use ADYNOVI 

 

Treatment with ADYNOVI will be started and supervised by a doctor who is experienced in the care 

of patients with haemophilia A. 

 

Your doctor will calculate your dose of ADYNOVIdepending on your condition and body weight, and 

on whether it is used for prevention or treatment of bleeding. The frequency of administration will 

depend on how well ADYNOVI is working for you. Usually, the replacement therapy with 

ADYNOVI is a life-long treatment. 

 

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

sure. 

 

Prevention of bleeding 

The usual dose of ADYNOVI is 40 to 50 IU per kg body weight, administered 2 times per week. 

 



 

117 

Treatment of bleeding 

The dose of ADYNOVI is calculated depending on your body weight and the factor VIII levels to be 

achieved. The target factor VIII levels will depend on the severity and location of the bleeding. 

If you think that the effect of ADYNOVI is insufficient, talk to your doctor. 

Your doctor will perform appropriate laboratory tests to make sure that you have adequate factor VIII 

levels. This is particularly important if you are having major surgery. 

 

Use in children and adolescents 

ADYNOVI can be used only in adolescents and adults (12 years and above). The dose in adolescents 

is also calculated to body weight and is the same dose as for adults. 

 

How ADYNOVI is given 

ADYNOVI is usually injected into a vein (intravenously) by your doctor or nurse. You or someone 

else might also administer ADYNOVI as an injection, but only after receiving adequate training. 

Detailed instructions for self-administration are given at the end of this package leaflet. 

 

If you use more ADYNOVI than you should 

Always use ADYNOVI exactly as your doctor has told you. You should check with your doctor if you 

are not sure. If you inject more ADYNOVI than recommended, tell your doctor as soon as possible. 

 

If you forget to use ADYNOVI 

Do not inject a double dose to make up for a forgotten dose. Proceed with the next injection as 

scheduled and continue as advised by your doctor. 

 

If you stop using ADYNOVI 

Do not stop using ADYNOVI without consulting your doctor. 

 

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

 

 

4. Possible side effects 

 

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

 

If severe, sudden allergic reactions (anaphylactic) occur, the injection must be stopped 

immediately. You must contact your doctor immediately if you have any of the following early 

symptoms of allergic reactions: 

 

- rash, hives, wheals, generalised itching, 
- swelling of lips and tongue, 
- difficulty in breathing, wheezing, tightness in the chest, 
- general feeling of being unwell, 
- dizziness and loss of consciousness. 
 

Severe symptoms, including difficulty in breathing and (nearly) fainting, require prompt emergency 

treatment. 

 

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. 

 

Common side effects (may affect up to 1 in 10 people) 

Headache, nausea, diarrhoea, rash 

 

Uncommon side effects (may affect up to 1 in 100 people) 

Flushing, allergic reaction (hypersensitivity) 



 

118 

Factor VIII inhibitors (for patients who have received previous treatment with Factor VIII (more than 

150 days of treatment)) 

 

Additional side effects in children 

Frequency, type and severity of adverse reactions in children are expected to be the same as in adults. 

 

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 ADYNOVI 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date, which is stated on the label and carton after EXP. The 

expiry date refers to the last day of that month. 

 

Store in a refrigerator (2 °C – 8 °C). 

Do not freeze. 

Keep the blister in the outer carton in order to protect from light. 

 

During the shelf life the powder vial may be kept at room temperature (up to 30 °C) for a single period 

not exceeding 3 months. In this case, this medicine expires at the end of this 3-month period or the 

expiration date printed on the product vial, whichever is earlier. Please record the end of the 3-month 

storage at room temperature on the product carton. The product may not be returned to refrigerated 

storage after storage at room temperature. Do not refrigerate the solution after preparation. 

 

Use the product within 3 hours once the powder is completely dissolved. 

 

The product is for single use only. Discard any unused solution appropriately. 

 

Do not throw away any medicines via waste water or household waste. Ask your pharmacist how to 

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

 

 

6. Contents of the pack and other information 

 

What ADYNOVI contains 

- The active substance is rurioctocog alfa pegol (pegylated human coagulation factor VIII 
produced by recombinant DNA technology). Each powder vial contains nominally 250, 500, 

or 1000 IU rurioctocog alfa pegol. 

- The solvent vial contains 2 ml of sterilised water for injections. 
 

- The other ingredients are mannitol, trehalose dihydrate, histidine, glutathion, sodium chloride, 
calcium chloride dihydrate, tris(hydroxymethyl)aminomethane, polysorbate 80. ADYNOVI 

contains sodium, see section 2. 

 

What ADYNOVI looks like and contents of the pack 

ADYNOVI is provided as a powder and solvent for solution for injection. The powder is a white to 

off-white crumbly powder. The solvent is a clear, colourless solution. After reconstitution, the solution 

is clear, colourless and free from foreign particles. 

 

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


 

119 

Marketing Authorisation Holder 

Baxalta Innovations GmbH 

Industriestrasse 67 

A-1221 Vienna 

Tel: +44(0)1256 894 959 

e-mail: medinfoEMEA@shire.com 

 

Manufacturer 

Baxalta Belgium Manufacturing SA 

Boulevard René Branquart 80 

B-7860 Lessines 

Belgium 

 

This leaflet was last revised in 

 

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

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

 

 

Instructions for preparation and administration 

 

ADYNOVI must not be mixed with other medicinal products or solvents. 

 

It is strongly recommended that every time ADYNOVI is administered, the name and batch number of 

the product are recorded. Peel-off labels are provided on the blister. 

 

Instructions for reconstitution 

• Do not use after the expiry date stated on the labels and carton. 

• Do not use if the lid is not completely sealed on the blister 

• Do not refrigerate the solution after preparation. 
 

1. If the product is still stored in a refrigerator, take the sealed blister (contains powder and solvent 

vials preassembled with the system for reconstitution) from the refrigerator and let it reach room 

temperature (between 15 °C and 25 °C). 

2. Wash your hands thoroughly using soap and warm water. 

3. Open the ADYNOVI blister by peeling away the lid. Remove the BAXJECT III system from 

the blister. 

4. Place the powder vial on a flat surface with the solvent vial on top (Figure 1). The solvent vial 

has a blue stripe. Do not remove the blue cap until instructed in a later step. 

5. With one hand holding the powder vial in the BAXJECT III system, press down firmly on the 

solvent vial with the other hand until the system is fully collapsed and the solvent flows down 

into the powder vial (Figure 2). Do not tilt the system until the transfer is complete. 

6. Verify that the solvent transfer is complete. Swirl gently until all material is dissolved 

(Figure 3). Be sure that the powder is completely dissolved, otherwise not all reconstituted 

solution will pass through the device filter. The product dissolves rapidly (usually in less 

than 1 minute). After reconstitution the solution should be clear, colourless and free from 

foreign particles. 

 

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


 

120 

Figure 1 Figure 2 Figure 3 

   
 

 

Instructions for injection 

Antiseptic technique (clean and low-germ conditions) is required during administration. 

 

Important note: 

• Inspect the prepared solution for particulate matter and discoloration prior to administration (the 
solution should be clear, colourless and free from particles). 

Do not use if the solution is not fully clear or not completely dissolved. 

 

1. Remove the blue cap from BAXJECT III. Do not draw air into the syringe. Connect the 

syringe to BAXJECT III. Use of a Luer-lock syringe is recommended. 

2. Turn the system upside down (powder vial now on top).Draw the reconstituted solution into the 

syringe by pulling the plunger back slowly. 

3. Disconnect the syringe; attach a butterfly needle to the syringe and inject the reconstituted 

solution into a vein. The solution should be administered slowly, at a rate as determined by the 

patient’s comfort level, not to exceed 10 ml per minute. (See section 4 “Possible side effects”). 

4. Discard any unused solution appropriately. 

 

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

 

The following information is intended for healthcare professionals only: 

 

On demand treatment 

In case of the following haemorrhagic events, factor VIII activity should not fall below the given 

plasma activity level (in % of normal or IU/dl) in the corresponding period. The following table can be 

used to guide dosing in bleeding episodes and surgery. 

 

 



 

121 

Table 1 Guide for dosing in bleeding episodes and surgery 

Degree of haemorrhage/type 

of surgical procedure 

Factor VIII level 

required (% or IU/dl) 

Frequency of doses (hours)/duration 

of therapy (days) 

Haemorrhage   

Early haemarthrosis, muscle 

bleeding or oral bleeding. 

20 – 40 Repeat injections every 12 to 24 hours. 

At least 1 day, until the bleeding 

episode, as indicated by pain, is 

resolved or healing is achieved. 

 

More extensive haemarthrosis, 

muscle bleeding or haematoma 

30 – 60 Repeat injections every 12 to 24 hours 

for 3 – 4 days or more until pain and 

acute disability are resolved. 

 

Life threatening haemorrhages. 60 – 100 Repeat injections every 8 to 24 hours 

until threat is resolved. 

Surgery   

Minor 

Including tooth extraction. 

30 – 60 Every 24 hours at least 1 day, until 

healing is achieved. 

 

Major 80 – 100 

 

(pre- and postoperative) 

Repeat injections every 8 to 24 hours 

until adequate wound healing, then 

continue therapy for at least 

another 7 days to maintain a factor VIII 

activity of 30% to 60% (IU/dl). 

 

Prophylaxis  

 

For long term prophylaxis, the recommended dose is 40 to 50 IU of ADYNOVI per kg bodyweight 

twice weekly in 3 to 4 day intervals. Adjustments of doses and administration intervals may be 

considered based on achieved FVIII levels and individual bleeding tendency (see section 5.2). 

 

Paediatric population  

 

On demand treatment dosing in paediatric patients (12 to 18 years of age) is the same as for adult 

patients. Prophylactic treatment for patients from 12 to <18 years is the same as for adult patients. The 

long-term safety of ADYNOVI in children below 12 years has not yet been established. Adjustments 

of doses and administration intervals may be considered based on achieved FVIII levels and individual 

bleeding tendency (see section 5.2).  

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
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	A. LABELLING
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