Idelvion

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
IDELVION 250 IU powder and solvent for solution for injection 
 
IDELVION 500 IU powder and solvent for solution for injection 
 
IDELVION 1000 IU powder and solvent for solution for injection 
 
IDELVION 2000 IU powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION  
 
IDELVION 250 IU powder and solvent for solution for injection 
One vial contains nominally 250 IU of recombinant fusion protein linking coagulation factor IX with 
albumin (rIX-FP), (INN = albutrepenonacog alfa). After reconstitution with 2.5 ml water for injections 
the solution contains 100 IU/ml of albutrepenonacog alfa. 
 
IDELVION 500 IU powder and solvent for solution for injection 
One vial contains nominally 500 IU of recombinant fusion protein linking coagulation factor IX with 
albumin (rIX-FP), (INN = albutrepenonacog alfa). After reconstitution with 2.5 ml water for injections 
the solution contains 200 IU/ml of albutrepenonacog alfa. 
 
IDELVION 1000 IU powder and solvent for solution for injection 
One vial contains nominally 1000 IU of recombinant fusion protein linking coagulation factor IX with 
albumin (rIX-FP), (INN = albutrepenonacog alfa). After reconstitution with 2.5 ml water for injections 
the solution contains 400 IU/ml of albutrepenonacog alfa. 
 
IDELVION 2000 IU powder and solvent for solution for injection 
One vial contains nominally 2000 IU of recombinant fusion protein linking coagulation factor IX with 
albumin (rIX-FP), (INN = albutrepenonacog alfa). After reconstitution with 5 ml water for injections 
the solution contains 400 IU/ml of albutrepenonacog alfa. 
 
The potency (International Units [IU]) is determined using an in-vitro activated partial thromboplastin 
time (aPTT)-based one-stage clotting assay calibrated against the World Health Organization (WHO) 
International Standard for factor IX concentrate.  
 
Albutrepenonacog alfa is a purified protein produced by recombinant DNA technology, generated by 
the genetic fusion of recombinant albumin to recombinant coagulation factor IX. The genetic fusion of 
the cDNA of human albumin to the cDNA of human coagulation factor IX enables the protein to be 
produced as a single recombinant protein and assures product homogeneity by avoiding chemical 
conjugation. The recombinant factor IX portion is identical to the Thr148 allelic form of plasma-
derived factor IX. The cleavable linker between the recombinant factor IX and albumin molecules is 
derived from the endogenous “activation peptide” in native factor IX.  
 
Excipient with known effect: 
Up to 25.8 mg (1.13 mmol) sodium per dose (bodyweight 70 kg). 
For the full list of excipients, see section 6.1. 
 
 



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3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection. 
Pale yellow to white powder and clear, colourless solvent for solution for injection. 
 
pH: 6.6 - 7.2 
 
Osmolality: 
IDELVION 250 IU powder and solvent for solution for injection 
175 – 215 mOsm/kg. 
 
IDELVION 500 IU powder and solvent for solution for injection 
260 – 300 mOsm/kg. 
 
IDELVION 1000 IU powder and solvent for solution for injection 
260 – 300 mOsm/kg. 
 
IDELVION 2000 IU powder and solvent for solution for injection 
260 – 300 mOsm/kg. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment and prophylaxis of bleeding in patients with haemophilia B (congenital factor IX 
deficiency). 
 
IDELVION can be used for all age groups. 
 
4.2 Posology and method of administration 
 
Treatment should be under the supervision of a physician experienced in the treatment of haemophilia 
B. 
 
Previously untreated patients  
The safety and efficacy of IDELVION in previously untreated patients have not yet been established. 
 
Treatment monitoring 
During the course of treatment, appropriate determination of factor IX levels is advised to guide the 
dose to be administered and the frequency of repeated infusions. Individual patients may vary in their 
responses to factor IX, 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 IX activity) is indispensable. 
 
When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining 
Factor IX activity in patients’ blood samples, plasma factor IX activity results can be significantly 
affected by both the type of aPTT reagent and the reference standard used in the assay. Measurement 
with a one-stage clotting assay using a kaolin based aPTT reagent or Actin FS aPTT reagent will 
likely result in an underestimation of activity level. This is of importance particularly when changing 
the laboratory and/or reagents used in the assay. 
 
Posology 
Dose and duration of the substitution therapy depend on the severity of the factor IX deficiency, on the 
location and extent of the bleeding and on the patient's clinical condition. 
 



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The number of units of factor IX administered is expressed in International Units (IU), which are 
related to the current WHO standard for factor IX products. Factor IX activity in plasma is expressed 
either as a percentage (relative to normal human plasma) or in International Units (relative to an 
International Standard for factor IX in plasma). 
 
One International Unit (IU) of factor IX activity is equivalent to that quantity of factor IX in one ml of 
normal human plasma.  
 
On demand treatment 
The calculation of the required dose of factor IX is based on the empirical finding that 1 International 
Unit (IU) factor IX per kg body weight is expected to increase the circulating level of factor IX by an 
average of 1.3 IU/dl (1.3 % of normal) in patients ≥ 12 years of age and by 1.0 IU/dl (1.0 % of normal) 
in patients < 12 years of age. The required dose is determined using the following formulae: 
 
Required dose (IU) = body weight (kg) x desired factor IX rise (% of normal or IU/dl) x {reciprocal of 
observed recovery (IU/kg per IU/dl)} 
 
Expected factor IX rise (IU/dl or % of normal) = Dose (IU) x Recovery (IU/dl per IU/kg)/body weight 
(kg) 
 
The amount to be administered and the frequency of administration should always be oriented to the 
clinical effectiveness in the individual case. 
 
Patients < 12 years of age 
For an incremental recovery of 1 IU/dl per 1 IU/kg, the dose is calculated as follows: 
Dose (IU) = body weight (kg) x desired factor IX increase (IU/dl) x 1 dl/kg 
 
Example  
1. A peak level of 50 % of normal is required in a 20 kg patient with severe haemophilia B. The 

appropriate dose would be 20 kg x 50 IU/dl x 1 dl/kg = 1000 IUs. 
 
2. A dose of 1000 IUs of IDELVION, administered to a 25 kg patient, should be expected to result 

in a peak post-injection factor IX increase of 1000 IUs/25 kg x 1.0 (IU/dl per IU/kg) = 40 IU/dl 
(40 % of normal). 

 
Patients ≥ 12 years of age 
For an incremental recovery of 1.3 IU/dl per 1 IU/kg, the dose is calculated as follows:  
Dose (IU) = body weight (kg) x desired factor IX increase (IU/dl) x 0.77 dl/kg 
 
Example  
3. A peak level of 50 % of normal is required in a 80 kg patient with severe haemophilia B.  The 

appropriate dose would be 80 kg x 50 IU/dl x 0.77 dl/kg = 3080 IUs. 
 
4. A dose of 2000 IUs of IDELVION, administered to a 80 kg patient, should be expected to result 

in a peak post-injection factor IX increase of 2000 IUs x 1.3 (IU/dl per IU/kg) 
/80 kg = 32.5 IU/dl (32.5 % of normal). 

 



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In the case of the following haemorrhagic events, the factor IX activity should not fall below the given 
plasma activity level (in % of normal or in IU/dl) in the corresponding period. The following table can 
be used to guide dosing in bleeding episodes and surgery: 

Degree of Haemorrhage /  
Type of surgical procedure  

Factor IX level 
required (%) (IU/dl) 

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

Haemorrhage  
Minor or moderate Haemarthrosis, 
muscle bleeding (except iliopsoas) 
or oral bleeding  

30 - 60 Single dose should be 
sufficient for majority of 
bleeds. Maintenance dose 
after 24 – 72 hours if there is 
further evidence of bleeding.  

Major haemorrhage 
Life threatening haemorrhages, 
deep muscle bleeding including 
iliopsoas  

60 - 100 Repeat every 24 – 72 hours 
for the first week, and then 
maintenance dose weekly 
until bleeding stops and 
healing is achieved. 

Minor surgery  
Including uncomplicated tooth 
extraction  

50 – 80 (initial level) Single dose may be sufficient 
for a majority of minor 
surgeries. If needed, 
maintenance dose can be 
provided after 24 – 72 hours 
until bleeding stops and 
healing is achieved.  

Major surgery  60 - 100 
(initial level) 

Repeat every 24 – 72 hours 
for the first week, and then 
maintenance dose 1 – 2 times 
per week until bleeding stops 
and healing is achieved. 

 
Prophylaxis  
For long term prophylaxis against bleeding in patients with severe haemophilia B, the usual doses are 
35 to 50 IU/kg once weekly. 
Some patients who are well-controlled on a once-weekly regimen might be treated with up to 75 IU/kg 
on an interval of 10 or 14 days. For patients >18 years, further extension of the treatment interval may 
be considered (see section 5.1). 
 
In some cases, especially in younger patients, shorter dosage intervals or higher doses may be 
necessary. 
 
After a bleeding episode during prophylaxis, patients should maintain their prophylaxis regimen as 
closely as possible, with 2 doses of IDELVION being administered at least 24 hours apart but longer 
as deemed suitable for the patient. 
 
Paediatric population  
For routine prophylaxis, the recommended dose regimen is 35 to 50 IU/kg once weekly (see sections 
5.1 and 5.2). 
 
Method of administration  
Intravenous use.  
 
For instructions on reconstitution of the medicinal product before administration, see section 6.6. 
 
The reconstituted preparation should be injected slowly intravenously at a rate comfortable for the 
patient up to a maximum of 5 ml/min. For detailed information regarding the administration of the 
reconstituted solution, see the instructions at the end of section 6.6. 
 



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4.3 Contraindications 
 
Hypersensitivity to the active substance (recombinant fusion protein linking coagulation factor IX with 
albumin (rIX-FP)) or to any of the excipients listed in section 6.1. 
 
Known allergic reaction to hamster protein. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Hypersensitivity 
Allergic type hypersensitivity reactions are possible with IDELVION. The product contains traces of 
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. It is recommended that the initial administration of factor IX 
should be performed under medical observation where proper medical care for allergic reactions could 
be provided. 
In case of shock, standard medical treatment for shock should be implemented. 
 
Inhibitors 
Formation of inhibitor to factor IX has been reported during factor replacement therapy with 
IDELVION in the treatment of haemophilia B. After repeated treatment with human coagulation 
factor IX products, patients should be monitored for the development of neutralising antibodies 
(inhibitors) that should be quantified in Bethesda Units (BU) using appropriate biological testing.  
 
There have been reports in the literature showing a correlation between the occurrence of a factor IX 
inhibitor and allergic reactions. Therefore, patients experiencing allergic reactions should be evaluated 
for the presence of an inhibitor. It should be noted that patients with factor IX inhibitors may be at an 
increased risk of anaphylaxis with subsequent challenge with factor IX.  
 
Because of the risk of allergic reactions with factor IX products, the initial administration of factor IX 
should, according to the treating physician’s judgement, be performed under medical observation 
where proper medical care for allergic reactions could be provided. 
 
Thromboembolism  
Because of the potential risk of thrombotic complications, clinical surveillance for early signs of 
thrombotic and consumptive coagulopathy should be initiated with appropriate biological testing when 
administering this product to patients with liver disease, to patients post-operatively, to new-born 
infants, or to patients at risk of thrombotic phenomena or DIC. In each of these situations, the benefit 
of treatment with IDELVION should be weighed against the risk of these complications. 
 
Cardiovascular events 
In patients with existing cardiovascular risk factors, substitution therapy with FIX may increase the 
cardiovascular risk. 
 
Catheter-related complications  
If a central venous access device (CVAD) is required, risk of CVAD-related complications including 
local infections, bacteraemia and catheter site thrombosis should be considered. 
 
Paediatric population  
The listed warnings and precautions apply both to adults and children. 
 
Elderly 



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Clinical studies of IDELVION did not include subjects aged 65 and over. It is not known whether they 
respond differently from younger subjects.  
 
Immune tolerance induction 
The safety and efficacy of using IDELVION for immune tolerance induction has not been established.  
 
Sodium content 
This medicinal product contains up to 25.8 mg (1.13 mmol) sodium per dose (bodyweight 70 kg) if the 
maximal dose (15 ml = 6000 IU) is applied. This is equivalent to 1.29% of the WHO recommended 
maximum daily intake of 2 g sodium for an adult. 
 
 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interactions of human coagulation factor IX products with other medicinal products have been 
reported. 
 
4.6 Fertility, pregnancy and lactation 
 
Animal reproduction studies have not been conducted with factor IX. Based on the rare occurrence of 
haemophilia B in women, experience regarding the use of factor IX during pregnancy and breast-
feeding is not available.  
 
Therefore, factor IX should be used during pregnancy and lactation only if clearly indicated. 
 
There is no information on the effects of factor IX on fertility. 
 
4.7 Effects on ability to drive and use machines 
 
IDELVION has no influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile  
Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the 
infusion site, chills, flushing, generalised urticaria, headache, hives, hypotension, lethargy, nausea, 
restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) have been observed 
rarely and may in some cases progress to severe anaphylaxis (including shock). In some cases, these 
reactions have progressed to severe anaphylaxis, and they have occurred in close temporal association 
with development of factor IX inhibitors (see also section 4.4). Nephrotic syndrome has been reported 
following attempted immune tolerance induction in haemophilia B patients with factor IX inhibitors 
and a history of allergic reaction.  
 
With the use of factor IX products obtained from CHO cells very rarely development of antibodies to 
hamster protein has been observed.  
 
Patients with haemophilia B may develop neutralising antibodies (inhibitors) to factor IX. 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. Inhibitor development was 
reported in an ongoing clinical study with previously untreated patients. Inhibitor development has 
been observed in previously treated patients in the post-marketing experience with IDELVION. 
There is a potential risk of thromboembolic episodes following the administration of factor IX 
products, with a higher risk for low purity preparations. The use of low purity factor IX products has 
been associated with instances of myocardial infarction, disseminated intravascular coagulation, 
venous thrombosis and pulmonary embolism. The use of high purity factor IX is rarely associated with 
such adverse reactions. 



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Tabulated list of adverse reactions 
Five open label clinical studies included 114 subjects with at least one exposure to IDELVION 
reporting 14 adverse reactions in 8 subjects. 
The table presented below is according to the MedDRA system organ classification (SOC and 
Preferred Term Level). 
 
Frequencies have been evaluated according to the following convention: very common (≥1/10); 
common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare 
(<1/10,000), not known (cannot be estimated from the available data).  
 
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 
 
 

MedDRA Standard System Organ Class Adverse reactions  Frequency per patient 

Blood and lymphatic disorders FIX inhibition/Inhibitor 

development 

Not known 

General disorders and administration site 
conditions Injection site reactions Common 

Nervous system disorders 
Headache Common 
Dizziness Common 

Immune system disorders Hypersensitivity Uncommon 

Skin and subcutaneous tissue disorders  
Rash Uncommon 
Eczema Uncommon 

 
Description of selected adverse reactions 
One previously untreated patient (PUP) from the ongoing clinical trial developed high titre inhibitor 
against factor IX. There are insufficient data to provide information on inhibitor incidence in PUPs. 
 
Paediatric Population  
Frequency, type and severity of adverse reactions in children are expected to be similar as in adults.  
 
Reporting of suspected adverse reactions  
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
No symptoms of overdose with IDELVION have been reported. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 

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


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Pharmacotherapeutic group: Antihaemorrhagics: Blood coagulation factor IX.  
ATC code: B02BD04 
 
Mechanism of action 
IDELVION (INN: albutrepenonacog alfa) is a recombinant coagulation factor IX. Prolongation of the 
half-life of IDELVION and the enhanced systemic exposure are achieved by fusion with recombinant 
albumin. Albumin is a natural, inert carrier protein in plasma with a half-life of approximately 
20 days. Genetic fusion of recombinant coagulation factor IX with albumin extends the half-life of 
factor IX (see section 5.2). 
IDELVION remains intact in the circulation until factor IX is activated, whereupon albumin is 
cleaved, releasing activated factor IX (FIXa) when it is needed for coagulation.  
 
Pharmacodynamic effects 
Haemophilia B is a sex linked hereditary disorder of blood coagulation due to decreased levels of 
factor IX and results in profuse bleeding into joints, muscles or internal organs, either spontaneously 
or as a result of accidental or surgical trauma. By replacement therapy the plasma levels of factor IX is 
increased, thereby enabling a temporary correction of the factor deficiency and correction of the 
bleeding tendencies. 
 
Factor IX is activated by factor VII/tissue factor complex in the extrinsic pathway as well as factor 
XIa in the intrinsic coagulation pathway. Activated factor IX, in combination with activated factor 
VIII, activates factor X. This results ultimately in the conversion of prothrombin to thrombin. 
Thrombin then converts fibrinogen into fibrin and a clot can be formed. Factor IX activity is absent or 
greatly reduced in patients with haemophilia B and substitution therapy may be required. 
 
General information on clinical efficacy and safety 
A phase 1/2 study evaluated the treatment efficacy and prevention of bleeding episodes of rIX-FP 
in 17 subjects (ages 13-46 years), 13 subjects in the prophylaxis arm received weekly prophylaxis 
with IDELVION for approximately 11 months, and 4 subjects in the on-demand arm received 
IDELVION upon occurrence of bleeding events. All 85 bleeding episodes were successfully 
treated with 1 or 2 doses of IDELVION. 
 
The efficacy of IDELVION has been evaluated in the open-label, uncontrolled part of a phase 2/3 
study, in which a total of 63 male, previously treated patients (PTPs) between 12 and 61 years of 
age received IDELVION either for prophylaxis once every 7-, 10- and/or 14-day intervals and/or 
for the treatment of bleeding episodes on an on-demand basis. All subjects had severe (FIX level 
<1%) or moderately severe (FIX level ≤ 2%) haemophilia B. Forty PTPs received IDELVION for 
prophylaxis. 
 
Subjects who received prophylactic treatment started with 35-50 IU/kg once weekly. A subgroup 
of patients switched to extended treatment intervals (every 10 or 14 days) with a recommended 
dose of 75 IU/kg and individual adjustments. 21 PTPs remained on the extended 14 day 
prophylaxis interval for additional treatment duration of 98 to 575 (median 386) days. From those 
subjects, 8 (38%) experienced at least one bleeding during the 14 day-prophylaxis, while they had 
no bleeding events during once weekly prophylaxis. Median Annualised Bleeding Rate (ABR) on 
7 day prophylaxis with IDELVION for all bleeds was 0.0 (range 0-6) and on 14 day-prophylaxis it 
was 1.08 (range 0-9.1).  
The long-term efficacy and safety of routine prophylaxis treatment was confirmed in an open-
label extension study for up to 5 years. In this study, a total of 59 PTPs ≥12 years (54 adults and 5 
adolescents) received IDELVION either for prophylaxis and/or for the treatment of bleeding 
episodes on an on-demand basis. 
 
Patients who received prophylactic treatment continued or started with 35-50 IU/kg once weekly. A 
subgroup of patients switched to extended treatment intervals (every 10, 14 or 21 days) with a 
recommended dose of 75 IU/kg (10 or 14 days) or 100 IU/kg (21 days). At the end of the study 14 
PTPs (24%) were on the 7 day prophylaxis interval, and a total of 11 (19%), 25 (42%) and 9 (15%) 
PTPs remained on the extended prophylaxis interval of 10, 14 and 21 days, respectively. During the 



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study, 2 PTPs (18%) in the 21-day regimen switched back to a more frequent dosing due to increased 
bleeding complications. The estimated median Annualised Bleeding Rates (ABRs) on 7-, 14-, and 21-
day prophylaxis with IDELVION for all bleeds were 1.3 (range 0-8), 0.9 (range 0-13), and 0.3 (range 
0-5), respectively. 
 
Currently available information support extension of treatment intervals for some patients though 
potentially associated with an increased risk for bleeding compared to a once weekly regimen.  
 
Of note, ABR is not comparable between different factor concentrates and between different 
clinical studies. 
 
Prophylaxis and control of bleeding in PTPs below 12 years 
The efficacy of IDELVION has been evaluated in a phase 3 study, in which a total of 27 male 
PTPs between 1 and 10 years (median age 6.0 years) with 12 patients < 6 years, received 
IDELVION for prophylaxis and control of bleeding episodes. All 27 subjects received weekly 
prophylaxis treatment with IDELVION for a mean time on study of 13.1 months (9, 18 months). 
 
Of the 106 bleeding episodes, the majority (94; 88.7%) was treated with single injection, 103; 
97.2% were treated with 1-2 injections. Haemostatic efficacy at resolution of a bleed was rated 
excellent or good in 96% of all treated bleeding episodes. 
 
The long-term efficacy and safety of routine prophylaxis treatment was confirmed in an open-
label extension study for up to 5 years. In the study, a total of 24 PTPs < 12 years received 
IDELVION either for prophylaxis and/or for the treatment of bleeding episodes on an on-demand 
basis.  
Patients who received prophylactic treatment continued with 35-50 IU/kg once weekly. A 
subgroup of patients switched to extended treatment intervals (every 10 or 14 days) with a 
recommended dose of 75 IU/kg. At the end of the study 17 PTPs (71%) were on the 7 day 
prophylaxis interval, and a total of 3 (12%), and 4 (17%) PTPs remained on the extended 
prophylaxis interval of 10 and 14 days, respectively. During the study, 4 PTPs (50%) in the 14-
day regimen switched back to a more frequent dosing due to increased bleeding complications. 
The estimated median Annualised Bleeding Rates (ABRs) for 7-, and 14-day prophylaxis with 
IDELVION for all bleeds were 2.0 (range 0-14), and 5.6 (range 0-8), respectively. 
 
Perioperative management:  
The safety and efficacy in the perioperative setting was evaluated in two pivotal Phase 3 studies 
and a long-term extension study. The per protocol efficacy analysis includes 30 surgeries 
performed in 21 patients between 5 and 58 years undergoing major or minor surgical, dental or 
other surgical invasive procedures. Dosing was individualized based on the subject’s PK and 
clinical response to treatment. A single preoperative bolus ranging from 14 to 163 IU/kg was used 
in 96.7% (n=29) of surgeries. Haemostatic efficacy was rated as excellent or good in all of the 
assessed procedures. During the 14-day postoperative period, patients received between 0 and 11 
infusions and total doses ranging from 0 to 444 IU/kg. 
 
 
Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
IDELVION in previously untreated patients in the treatment and prophylaxis of bleeding in 
haemophilia B (see section 4.2 for information on paediatric use). 
 
5.2 Pharmacokinetic properties 
 
Adult population 
The pharmacokinetics (PK) of IDELVION were evaluated following an intravenous injection of a 
single dose of 25, 50 and 75 IU/kg. The PK parameters following a single injection of 50 IU/kg 
IDELVION (see table below) were based on plasma factor IX activity measured by the one-stage 
clotting assay. The mean factor IX activity at day 7 and day 14 was 13.76% and 6.10%, respectively, 



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after a single dose of 50 IU/kg IDELVION.  Repeat PK assessment for up to 30 weeks demonstrated a 
stable pharmacokinetic profile and incremental recovery was consistent over time. 
Trough levels of 5-10% have been targeted in clinical trials for achieving bleeding control while on 
prophylaxis. PK simulations suggest the time to reach 5% plasma FIX activity following a single 
injection of 50 IU/kg IDELVION to be 12.5 days for adults. 
 
Pharmacokinetic Parameters for subjects with severe haemophilia (Median (min, max)) 
following a single injection of IDELVION in Adults 

PK Parameters 50 IU/kg (N=22) 

IRa  
(IU/dl)/(IU/kg) 1.18 (0.86, 1.86) 

Cmaxa 
(IU/dl) 62.7 (40.5, 87.0) 

AUC0-inf 
(h*IU/dl) 6638 (2810, 9921) 

Elimination t1/2 
(h) 95.3 (51.5, 135.7) 

CL 
(ml/h/kg) 0.875 (0.748, 1.294) 

a = corrected for baseline levels 
IR = incremental recovery; AUC = area under the factor IX activity time curve; CL = body weight adjusted 
clearance; Elimination t1/2 = Elimination half-life 
 
Paediatric population  
Pharmacokinetic (PK) parameters of IDELVION were evaluated in adolescents (12 to <18 years of 
age) and children (1 to <12 years of age) following an intravenous injection of a single dose of 
50 IU/kg. PK parameters (presented below) were estimated based on the plasma factor IX activity over 
time profile measured by the one-stage clotting assay.  
 
Comparison of Pharmacokinetic Parameters of IDELVION by Age Category (Median (min, 
max)) Following a Single Injection of 50 IU/kg IDELVION 

PK Parameters 1 to <6 years (N=12) 
6 to <12 years 

(N=15) 
12 to <18 years 

(N=5) 
IRa 
(IU/dl)/(IU/kg) 

 
0.968 (0.660, 1.280) 

 
1.07 (0.70, 1.47) 

 
1.11 (0.84, 1.61) 

Cmaxa  
(IU/dl) 

 
48.2 (33.0, 64.0) 

 
50.5 (34.9, 73.6) 

 
55.3 (40.5, 80.3) 

AUC0-inf  
(h*IU/dl) 

 
4301 (2900, 8263) 

 
4718 (3212, 7720) 

 
4804 (2810, 9595) 

Elimination t1/2  
(h) 

 
86.2 (72.6, 105.8) 

 
89.3 (62.1, 123.0) 

 
88.8 (51.5, 130.0) 

CL 
(ml/h/kg) 

 
1.16 (0.61, 1.72) 

 
1.06 (0.65, 1.56) 

 
1.04 (0.52, 1.67) 

a = corrected for baseline levels 
IR = incremental recovery; AUC = area under the factor IX activity time curve; CL = body weight adjusted 
clearance; Elimination t1/2 = Elimination half-life 
 
Trough levels of 5-10% have been targeted in clinical trials for achieving bleeding control while on 
prophylaxis. PK simulations suggest the time to reach 5% plasma FIX activity following a single 



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injection of 50 IU/kg IDELVION to be 7 days for 1-<6years, 9 days for 6-<12 years and 11 days for 
12-<18 years of age).  
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, single and repeat dose toxicity, genotoxicity, thrombogenicity and local tolerability.  
 
No investigations on carcinogenicity and reproductive toxicology have been conducted. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder:  
Tri-sodium citrate dihydrate, Polysorbate 80, Mannitol, Sucrose, HCl (for pH adjustment).  
 
Solvent:  
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products, diluents or solvents except those mentioned in section 6.1. 
 
6.3 Shelf life 
 
3 years 
 
After reconstitution the chemical and physical in-use stability has been demonstrated for 8 hours at 
2-25 °C). From a microbiological point of view, the product should be used immediately. If not used 
immediately, in-use storage times and conditions prior to use are in the responsibility of the user.  
 
6.4 Special precautions for storage 
 
Do not store above 25 °C. 
 
Do not freeze. Keep vials 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 
 
IDELVION 250 IU powder and solvent for solution for injection 
Powder (250 IU) in a 6 ml vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap 
(aluminium). 
2.5 ml of solvent in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap (aluminium). 
 
IDELVION 500 IU powder and solvent for solution for injection 
Powder (500 IU) in a 6 ml vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap 
(aluminium). 
2.5 ml of solvent in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap (aluminium). 
 
IDELVION 1000 IU powder and solvent for solution for injection 
Powder (1000 IU) in a 6 ml vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap 
(aluminium). 



13 

2.5 ml of solvent in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap (aluminium). 
 
IDELVION 2000 IU powder and solvent for solution for injection 
Powder (2000 IU) in a 10 ml vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap 
(aluminium). 
5 ml of solvent in a vial (type I glass), with a stopper (rubber) a disc (plastic) and a cap (aluminium). 
 
The powder vials are available with or without RFID (radio-frequency identification). 
The use of a RFID-controlled automated infusion pump requires the RFID tagged powder vials. For 
identification purpose, RFID emblem is included on the packages containing RFID tagged powder 
vials. 
 

 
 
 
Presentations 
 
Each pack contains: 
 
IDELVION 250 IU powder and solvent for solution for injection: 
1 vial with powder (with or without RFID tag) 
1 vial with 2.5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 5 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
IDELVION 500 IU powder and solvent for solution for injection 
1 vial with powder (with or without RFID tag) 
1 vial with 2.5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 5 ml syringe 
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
IDELVION 1000 IU powder and solvent for solution for injection 
1 vial with powder (with or without RFID tag) 
1 vial with 2.5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 5 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
IDELVION 2000 IU powder and solvent for solution for injection 
1 vial with powder (with or without RFID tag) 
1 vial with 5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe  
1 venipuncture set 



14 

2 alcohol swabs 
1 non-sterile plaster 
 
Not all pack sizes may be marketed. 
 
6.6 Special precautions for disposal and other handling 
 
General instructions 
- The reconstituted solution should be clear or slightly opalescent, yellow to colourless. After 

filtering/withdrawal (see below) the reconstituted product should be inspected visually for 
particulate matter and discoloration prior to administration.  

- Do not use solutions that are cloudy or have deposits.  
- Reconstitution and withdrawal must be carried out under aseptic conditions. 
 
Reconstitution 
Bring the solvent to room temperature (below 25 °C). Ensure product and solvent vial flip caps are 
removed and the stoppers are treated with an antiseptic solution and allowed to dry prior to opening 
the Mix2Vial package. 
 

 1 

1. Open the Mix2Vial by peeling off the lid. Do 
not remove the Mix2Vial from the blister 
package! 

 2 

2. Place the solvent vial on an even, clean surface 
and hold the vial tight. Take the Mix2Vial 
together with the blister package and push the 
spike of the blue adapter end straight down 
through the solvent vial stopper. 

 3 

3. Carefully remove the blister package from the 
Mix2Vial set by holding at the rim, and pulling 
vertically upwards. Make sure that you only 
pull away the blister package and not the 
Mix2Vial set. 

 4 

4. Place the powder vial on an even and firm 
surface. Invert the solvent vial with the 
Mix2Vial set attached and push the spike of the 
transparent adapter end straight down 
through the product vial stopper. The solvent 
will automatically flow into the product vial. 

 5 

5. With one hand grasp the powder-side of the 
Mix2Vial set and with the other hand grasp the 
solvent-side and unscrew the set carefully 
counterclockwise into two pieces.  
Discard the solvent vial with the blue Mix2Vial 
adapter attached. 



15 

 6 

6. Gently swirl the product vial with the 
transparent adapter attached until the substance 
is fully dissolved. Do not shake. 

 7 

7. Draw air into an empty, sterile syringe. While 
the product vial is upright, connect the syringe 
to the Mix2Vial's Luer Lock fitting by screwing 
clockwise. Inject air into the product vial. 

 
Withdrawal and application 
 

 8 

8. While keeping the syringe plunger pressed, turn 
the system upside down and draw the solution 
into the syringe by pulling the plunger back 
slowly. 

 9 

9. Now that the solution has been transferred into 
the syringe, firmly hold on to the barrel of the 
syringe (keeping the syringe plunger facing 
down) and disconnect the transparent Mix2Vial 
adapter from the syringe by unscrewing 
counterclockwise. 

 
For injection of IDELVION, only the provided administration sets should be used because treatment 
failure can occur as a consequence of factor IX adsorption to the internal surface of some injection 
equipment. 
 
Care should be taken that no blood enters the syringe filled with product, as there is a risk that the 
blood could coagulate in the syringe and fibrin clots could therefore be administered to the patient.  
 
The IDELVION solution must not be diluted. 
 
The reconstituted solution should be administered by slow intravenous injection either manually or via 
an optional RFID-controlled automated infusion pump. The rate of administration should be 
determined by the patient’s comfort level, up to a maximum of 5 ml/min. In case of administration 
with a RFID-controlled automated infusion pump the detailed handling instructions provided with the 
pump should be followed. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 



16 

 
CSL Behring GmbH 
Emil-von-Behring-Str. 76 
35041 Marburg 
Germany 
 
 
8. MARKETING AUTHORIZATION NUMBER(S) 
 
Non-RFID: 
EU/1/16/1095/001 
EU/1/16/1095/002 
EU/1/16/1095/003 
EU/1/16/1095/004 
 
RFID (radio-frequency identification): 
EU/1/16/1095/005 
EU/1/16/1095/006 
EU/1/16/1095/007 
EU/1/16/1095/008 
 
9. DATE OF FIRST AUTHORIZATION/RENEWAL OF THE AUTHORIZATION 
 
Date of first authorisation: 11 May 2016 
 
 
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/


17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 

 
A. MANUFACTURER OF THE BIOLOGICAL ACTIVE 

SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR 
BATCH RELEASE 

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 

 

 



18 

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

Name and address of the manufacturer of the biological active substance 

CSL Behring GmbH 
Emil-von-Behring Strasse 76 
35041 Marburg 
Germany 
 

 
Name and address of the manufacturer responsible for batch release 

CSL Behring GmbH 
Emil-von-Behring Strasse 76 
35041 Marburg 
Germany 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

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

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION  

• Periodic safety update reports  
 

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. 

The marketing authorisation holder shall submit the first periodic safety update report for this 
product within 6 months following authorisation. 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT 

• Risk Management Plan (RMP) 
 

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP. 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new 
information being received that may lead to a significant change to the benefit/risk profile 
or as the result of an important (pharmacovigilance or risk minimisation) milestone being 
reached. 

  



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 



20 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
 

  



21 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
Carton 250 IU 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
IDELVION 250 IU 
powder and solvent for solution for injection 
Albutrepenonacog alfa 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Albutrepenonacog alfa 250 IU 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: Tri-sodium citrate dihydrate, Polysorbate 80, Mannitol, Sucrose, HCl  
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection 
1 vial with powder: 250 IU albutrepenonacog alfa (100 IU/ml after reconstitution)  
1 vial with 2.5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
 
1 disposable 5 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous 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 
 
RFID emblem included on carton containing RFID tagged powder vial 

 
 
8. EXPIRY DATE 
 
EXP 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. Do not freeze.  



22 

Keep the vials in the outer carton in order to protect from light. 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
Non-RFID: 
EU/1/16/1095/001 
 
RFID: 
EU/1/16/1095/005 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
IDELVION 250 IU 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



23 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Powder vial 250 IU 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
IDELVION 250 IU powder for solution for injection 
Albutrepenonacog alfa 
For intravenous use 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
RFID emblem included on RFID tagged vial label 

 



24 

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



25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
Carton 500 IU 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
IDELVION 500 IU 
powder and solvent for solution for injection 
Albutrepenonacog alfa 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Albutrepenonacog alfa 500 IU 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: Tri-sodium citrate dihydrate, Polysorbate 80, Mannitol, Sucrose, HCl 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection 
1 vial with powder: 500 IU albutrepenonacog alfa (200 IU/ml after reconstitution)   
1 vial with 2.5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 5 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous 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 
 
RFID emblem included on carton containing RFID tagged powder vial 

 
 
8. EXPIRY DATE 
 
EXP 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. Do not freeze.  



26 

Keep the vials in the outer carton in order to protect from light. 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
Non-RFID: 
EU/1/16/1095/002 
 
RFID: 
EU/1/16/1095/006 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
IDELVION 500 IU 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



27 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Powder vial 500 IU 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
IDELVION 500 IU powder for solution for injection 
Albutrepenonacog alfa 
For intravenous use 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
RFID emblem included on RFID tagged vial label 

 
 



28 

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



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
Carton 1000 IU 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
IDELVION 1000 IU 
powder and solvent for solution for injection 
Albutrepenonacog alfa 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Albutrepenonacog alfa 1000 IU 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: Tri-sodium citrate dihydrate, Polysorbate 80, Mannitol, Sucrose, HCl 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection 
1 vial with powder: 1000 IU albutrepenonacog alfa (400 IU/ml after reconstitution)   
1 vial with 2.5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 5 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous 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 
 
RFID emblem included on carton containing RFID tagged powder vial 

 
 
8. EXPIRY DATE 
 
EXP 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. Do not freeze.  
Keep the vials in the outer carton in order to protect from light. 



30 

 
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 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
Non-RFID: 
EU/1/16/1095/003 
 
RFID: 
EU/1/16/1095/007 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
IDELVION 1000 IU 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



31 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Powder vial 1000 IU 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
IDELVION 1000 IU powder for solution for injection 
Albutrepenonacog alfa 
For intravenous use 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
RFID emblem included on RFID tagged vial label 

 



32 

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



33 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
Carton 2000 IU 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
IDELVION 2000 IU 
powder and solvent for solution for injection 
Albutrepenonacog alfa 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Albutrepenonacog alfa 2000 IU 
 
3. LIST OF EXCIPIENTS 
 
Other ingredients: Tri-sodium citrate dihydrate, Polysorbate 80, Mannitol, Sucrose, HCl 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection 
1 vial with powder: 2000 IU albutrepenonacog alfa (400 IU/ml after reconstitution)    
1 vial with 5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
For intravenous 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 
 
RFID emblem included on carton containing RFID tagged powder vial 

 
 
8. EXPIRY DATE 
 
EXP 
 
9. SPECIAL STORAGE CONDITIONS 
 
Do not store above 25 °C. Do not freeze.  
Keep the vials in the outer carton in order to protect from light. 



34 

 
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 
 
CSL Behring GmbH, 35041 Marburg, Germany 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
Non-RFID: 
EU/1/16/1095/004 
 
RFID: 
EU/1/16/1095/008 
 
13. BATCH NUMBER 
 
Lot 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
IDELVION 2000 IU 
 
 
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  
Powder vial 2000 IU 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
IDELVION 2000 IU powder for solution for injection 
Albutrepenonacog alfa 
For intravenous use 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
 
6. OTHER 
 
RFID emblem included on RFID tagged vial label 

 
 



36 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS  
Solvent vial label 5 ml 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Water for injections 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
4. BATCH NUMBER 
 
Lot 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
5 ml 
 
6. OTHER 
  



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
Carton administration set (inner box) 

 
1. NAME OF THE MEDICINAL PRODUCT 

 
Administration set 
 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
-not applicable- 
 

3. LIST OF EXCIPIENTS 
 
-not applicable- 
 

4. PHARMACEUTICAL FORM AND CONTENTS 
 
-not applicable- 
 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
-not applicable- 
 

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

 
-not applicable- 
 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
-not applicable- 
 

8. EXPIRY DATE 
 
Exp. date 
 

9. SPECIAL STORAGE CONDITIONS 
 
-not applicable- 
 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR 
WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
-not applicable- 
 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
CSL Behring 
 

12. MARKETING AUTHORISATION NUMBER(S) 
 
-not applicable- 
  



38 

13. BATCH NUMBER 
 
Lot No. 
 

14. GENERAL CLASSIFICATION FOR SUPPLY 
 
-not applicable- 
 

15. INSTRUCTIONS ON USE 
 
-not applicable- 
 

16. INFORMATION IN BRAILLE 
 
-not applicable- 

  



39 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 
 

  



40 

Package Leaflet: Information for the user 
 
 

IDELVION 250 IU powder and solvent for solution for injection 
IDELVION 500 IU powder and solvent for solution for injection  
IDELVION 1000 IU powder and solvent for solution for injection 
IDELVION 2000 IU powder and solvent for solution for injection  

Albutrepenonacog alfa 
 

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 further questions, ask your doctor, pharmacist or nurse. 
• 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, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet:  
1. What IDELVION is and what it is used for 
2. What you need to know before you use IDELVION 
3. How to use IDELVION 
4. Possible side effects 
5. How to store IDELVION  
6. Contents of the pack and other information 
 
 
1. What IDELVION is and what it is used for  
 
What is IDELVION? 
 
IDELVION is a haemophilia medicine that replaces a natural blood clotting (coagulation) factor IX. 
The active substance in IDELVION is albutrepenonacog alfa (recombinant fusion protein linking 
coagulation factor IX with albumin (rIX-FP)). 
 
Factor IX is involved in blood clotting. Patients with haemophilia B have a lack of this factor which 
means that their blood does not clot as quickly as it should so there is an increased tendency to bleed. 
IDELVION works by replacing factor IX in haemophilia B patients to enable their blood to clot. 
 
What is IDELVION used for? 
 
IDELVION is used to prevent or to halt bleeding caused by the lack of factor IX in patients of all age 
groups with haemophilia B (also called congenital factor IX deficiency or Christmas disease). 

 
 
2. What you need to know before you use IDELVION  
 
Do not use IDELVION  
• If you are allergic to the active ingredient (albutrepenonacog alfa) or any of the other ingredients 

(listed in section 6). 
• If you are allergic to hamster proteins. 
 



41 

Warnings and precautions 
 
Traceability 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Talk to your doctor, pharmacist or nurse before using IDELVION. 
 
• Allergic (hypersensitivity) reactions are possible. The product contains traces of hamster 

proteins (see also “Do not use IDELVION”). If symptoms of allergic reactions occur, you 
should stop using the medicine immediately and contact your doctor. Your doctor should 
inform you of the early signs of hypersensitivity reactions. These include hives, generalised 
skin rash, tightness of the chest, wheezing, low blood pressure (hypotension), and anaphylaxis 
(a serious allergic reaction that causes severe difficulty in breathing, or dizziness). 

• Because of the risk of allergic reactions with factor IX, your initial administration of 
IDELVION should be performed under medical observation where proper medical care for 
allergic reactions can be provided.  

• The formation of inhibitors (neutralising antibodies) is a known complication that has been 
reported during treatment with IDELVION, which stops the treatment from working properly. If 
your bleeding is not being controlled with IDELVION, tell your doctor immediately. You 
should be monitored carefully for the development of inhibitors.  

• If you suffer from liver or cardiac disease or if you have recently had major surgery, please 
inform your doctor, as there is an increased risk for blood clotting (coagulation) complications. 

• If you need a central venous access device (CVAD for injection of IDELVION), the risk of 
complications including local infections, bacteria in the blood (bacteremia) and the formation of 
a blood clot in the blood vessel (thrombosis) where the catheter is inserted should be considered 
by your doctor. 

 
Other medicines and IDELVION 
• Tell your doctor or pharmacist if you are taking, have recently taken or might take any other 

medicines. 
 
Pregnancy and breast-feeding 
• If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, 

ask your doctor or pharmacist for advice before taking this medicine.  
• During pregnancy and breast-feeding, IDELVION should be given only if it is clearly needed. 
 
Driving and using machines 
IDELVION does not effect your ability to drive and use machines. 
 
IDELVION contains sodium 
IDELVION contains up to 25.8 mg (1.13 mmol) sodium per dose (bodyweight 70 kg) if the maximal 
dose (15 ml = 6000 IU) is applied. This is equivalent to 1.29% of the recommended maximum daily 
dietary intake of sodium (main component of cooking/table salt) for an adult. 
 
 
 
3. How to use IDELVION  
 
Your treatment should be started and monitored by a doctor who is experienced in the treatment of 
blood clotting disorders. 
 
Dose 
 
Your doctor will calculate the dose of IDELVION you need. The amount of IDELVION you need to 
take and the duration of treatment depend on: 
• the severity of your disease 



42 

• the site and intensity of the bleeding 
• your clinical condition and response 
• your body weight 
 
Follow the directions given to you by your doctor. 
 
If you use more IDELVION than you should  
Please contact your doctor immediately if you inject more IDELVION than your doctor recommends. 
 
If you stop using IDELVION  
Do not stop using IDELVION without consulting your doctor. 
 
Reconstitution and application 
 
General Instructions 
• The powder must be mixed with the solvent (liquid) and withdrawn from the vial under aseptic 

conditions. 
• IDELVION must not be mixed with other medicines or solvents except those mentioned in 

section 6. 
• The solution should be clear or slightly opalescent, yellow to colourless, i.e. it might be 

sparkling when held up to the light but must not contain any obvious particles. After filtering or 
withdrawal (see below) the solution should be checked by eye, before it is used. Do not use the 
solution if it is cloudy or if it contains flakes or particles. 

• Any unused product or waste material should be disposed of in accordance with local 
requirements and as instructed by your doctor.  

 
Reconstitution 
Without opening the vials, warm the IDELVION powder and the liquid to room or body temperature. 
This can be done either by leaving the vials at room temperature for about an hour, or by holding them 
in your hands for a few minutes.  
DO NOT expose the vials to direct heat. The vials must not be heated above body temperature (37 °C). 
 
Carefully remove the protective caps from the vials, and clean the exposed rubber stoppers with an 
alcohol swab. Allow the vials to dry before opening the Mix2Vial package (which contains the filter 
transfer device), then follow the instructions given below. 
 

 1 

1. Open the Mix2Vial by peeling off the lid. Do 
not remove the Mix2Vial from the blister 
package! 

 2 

2. Place the solvent vial on an even, clean surface 
and hold the vial tight. Take the Mix2Vial 
together with the blister package and push the 
spike of the blue adapter end straight down 
through the solvent vial stopper. 

 3 

3. Carefully remove the blister package from the 
Mix2Vial set by holding at the rim, and pulling 
vertically upwards. Make sure that you only 
pull away the blister package and not the 
Mix2Vial set. 



43 

 4 

4. Place the powder vial on an even and firm 
surface. Invert the solvent vial with the 
Mix2Vial set attached and push the spike of the 
transparent adapter end straight down 
through the product vial stopper. The solvent 
will automatically flow into the product vial. 

 5 

5. With one hand grasp the powder-side of the 
Mix2Vial set and with the other hand grasp the 
solvent-side and unscrew the set carefully 
counterclockwise into two pieces.  
Discard the solvent vial with the blue Mix2Vial 
adapter attached. 

 6 

6. Gently swirl the product vial with the 
transparent adapter attached until the substance 
is fully dissolved. Do not shake. 

 7 

7. Draw air into an empty, sterile syringe. While 
the product vial is upright, connect the syringe 
to the Mix2Vial's Luer Lock fitting by screwing 
clockwise. Inject air into the product vial. 

 
Withdrawal and Application 
 

 8 

8. While keeping the syringe plunger pressed, turn 
the system upside down and draw the solution 
into the syringe by pulling the plunger back 
slowly. 

 9 

9. Now that the solution has been transferred into 
the syringe, firmly hold on to the barrel of the 
syringe (keeping the syringe plunger facing 
down) and disconnect the transparent Mix2Vial 
adapter from the syringe by unscrewing 
counterclockwise. 

 
Use the venipuncture kit supplied with the product, insert the needle into a vein. Let blood flow back 
to the end of the tube. Attach the syringe to the threaded, locking end of the venipuncture kit. Inject 
the reconstituted solution slowly (as comfortable for you, up to a maximum of 5 ml/min) either 
manually or via an optional RFID-controlled automated infusion pump into the vein following 



44 

the instructions given to you by your doctor. In case of administration with a RFID-controlled 
automated infusion pump the detailed handling instructions provided with the pump should be 
followed. Take care not to get any blood in the syringe containing the product.  
 
Check yourself for any side effects that might happen straight away. If you have any side effects that 
might be related to the administration of IDELVION, the injection should be stopped (see also 
sections 2 and 4). 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Please contact your doctor immediately: 
• if you notice symptoms of allergic reactions (see below)  
• if you notice that the medicine stops working properly 
 
The following side effects have been observed with factor IX medicines: 
• Allergic-type hypersensitivity reactions are possible and may include the following symptoms: 

hives, skin rashes (generalised urticaria), tightness of the chest, wheezing, low blood pressure 
(hypotension) and anaphylaxis (a serious reaction that causes severe difficulty in breathing or 
dizziness). If this happens, you should stop using the medicine immediately and contact your 
doctor.  

• Inhibitors: the medicine stops working properly (continuous bleeding). You may develop an 
inhibitor (neutralising antibody) to factor IX, in which case factor IX will not work properly any 
more. If this happens, you should stop using the medicine immediately and contact your doctor.  

 
The following side effects have been observed with IDELVION commonly (may affect up to 1 in 10 
people): 
• Headache 
• Injection site reactions 
• Dizziness 
 
The following side effects occurred uncommonly (may affect up to 1 in 100 people): 
• Allergic reactions (Hypersensitivity) 
• Rash 
• Eczema 
 
The following side effects have been reported but it is not known how many people may be affected: 
• Development of neutralising antibodies (inhibitors) to IDELVION 
 
• Side effects in children and adolescents 
Side effects 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, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store IDELVION   
 
• Keep this medicine out of the sight and reach of children. 

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


45 

• Do not use this medicine after the expiry date, which is stated on the label and carton. 
• Do not store above 25 °C.  
• Do not freeze.  
• Keep the vial in the outer carton in order to protect from light. 
• The reconstituted product should preferably be used immediately.  
• If the reconstituted product is not administered immediately, storage times and conditions prior 

to use are in the responsibility of the user. 
 
 
6. Contents of the pack and other information 
 
What IDELVION contains 
 
The active substance is: 
250 IU per vial; after reconstitution with 2.5 ml of water for injections the solution contains 100 IU/ml 
of albutrepenonacog alfa. 
500 IU per vial; after reconstitution with 2.5 ml of water for injections the solution contains 200 IU/ml 
of albutrepenonacog alfa. 
1000 IU per vial; after reconstitution with 2.5 ml of water for injections the solution contains 
400 IU/ml of albutrepenonacog alfa. 
2000 IU per vial; after reconstitution with 5 ml of water for injections the solution contains 400 IU/ml 
of albutrepenonacog alfa. 
 
The other ingredients are: 
Tri-sodium citrate dihydrate, polysorbate 80, mannitol, sucrose, and HCl (for pH adjustment)  
See last paragraph of section 2. 
Solvent: Water for injections 
 
What IDELVION looks like and contents of the pack 
 
IDELVION is presented as a pale yellow to white powder and is supplied with water for injections as 
solvent. 
The reconstituted solution should be clear to slightly opalescent, yellow to colourless i.e. it might 
sparkle when held up to the light but must not contain any obvious particles.  
 
The powder vials are available with or without RFID (radio-frequency identification). 
The use of a RFID-controlled automated infusion pump requires the RFID tagged powder vials. 
For identification purpose, RFID emblem is included on the packages containing RFID tagged 
powder vials. 
 

 
 
Presentations 
 
One pack with 250, 500 or 1000 IU containing: 
1 vial with powder (with or without RFID tag) 
1 vial with 2.5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 5 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
One pack with 2000 IU containing: 



46 

1 vial with powder (with or without RFID tag) 
1 vial with 5 ml water for injections 
1 filter transfer device 20/20 
One inner box containing: 
1 disposable 10 ml syringe  
1 venipuncture set 
2 alcohol swabs 
1 non-sterile plaster 
 
Not all pack sizes may be marketed. 
 
 
Marketing Authorization Holder and Manufacturer 
 
CSL Behring GmbH 
Emil-von-Behring-Straße 76 
35041 Marburg 
Germany 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
 
België/Belgique/Belgien 
CSL Behring NV 
Tél/Tel: +32 15 28 89 20 
 

Lietuva 
CSL Behring GmbH 
Tel: +49 69 30584437 
 

България 
Ей енд Ди Фарма България ЕАД 
Тел: +359 2 810 3949  
 

Luxembourg/Luxemburg 
CSL Behring NV 
Tél/Tel: +32 15 28 89 20 
 

Česká republika 
CSL Behring s.r.o. 
Tel: + 420 702 137 233 
 

Magyarország 
CSL Behring Kft. 
Tel.: +36 1 213 4290 
 

Danmark 
CSL Behring AB 
Tel: +46 8 544 966 70 
 

Malta 
AM Mangion Ltd. 
Tel: +356 2397 6333 
 

Deutschland 
CSL Behring GmbH 
Tel: +49 69 30584437 
 

Nederland 
CSL Behring BV 
Tel: + 31 85 111 96 00 
 

Eesti 
CSL Behring GmbH 
Tel: +49 69 30584437 
 

Norge 
CSL Behring AB 
Tlf: +46 8 544 966 70 
 

Ελλάδα 
CSL Behring ΕΠΕ 
Τηλ: +30 210 7255 660 
 

Österreich 
CSL Behring GmbH 
Tel: +43 1 80101 2463 
 

España 
CSL Behring S.A. 
Tel: +34 933 67 1870 
 

Polska 
CSL Behring Sp.z o.o. 
Tel: +48 22 213 22 65 
 

France 
CSL Behring S.A. 

Portugal 
CSL Behring Lda 



47 

Tél: + 33 –(0)-1 53 58 54 00 
 

Tel: +351 21 782 62 30 
 

Hrvatska 
Marti Farm d.o.o. 
Tel: +385 1 5588297 
 

România 
Prisum International Trading srl 
Tel: +40 21 322 0171 
 

Ireland 
CSL Behring GmbH 
Tel: +49 69 30517254 
 

Slovenija 
MediSanus d.o.o. 
Tel: +386 1 25 71 496 
 

Ísland 
CSL Behring AB 
Sími: +46 8 544 966 70 
 

Slovenská republika 
CSL Behring s.r.o. 
Tel: + 421 911 653 862 
 

Italia 
CSL Behring S.p.A. 
Tel: +39 02 34964 200 
 

Suomi/Finland 
CSL Behring AB 
Puh/Tel: +46 8 544 966 70 
 

Κύπρος 
CSL Behring ΕΠΕ 
Τηλ: +30 210 7255 660 
 

Sverige 
CSL Behring AB 
Tel: +46 8 544 966 70 
 

Latvija 
CSL Behring GmbH 
Tel: +49 69 30584437 
 

United Kingdom 
CSL Behring UK Ltd. 
Tel: +44 1444 447405 
 

 
This leaflet was last revised in {MM/YYYY}. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu. 
 
 
---------------------------------------------------------------------------------------------------------- 
 
 
The following information is intended for healthcare professionals only: 
 
 
Posology 
Dose and duration of the substitution therapy depend on the severity of the factor IX deficiency, on the 
location and extent of the bleeding and on the patient's clinical condition. 
 
The number of units of factor IX administered is expressed in International Units (IU), which are 
related to the current WHO standard for factor IX products. Factor IX activity in plasma is expressed 
either as a percentage (relative to normal human plasma) or in International Units (relative to an 
International Standard for factor IX in plasma). 
 
One International Unit (IU) of factor IX activity is equivalent to that quantity of factor IX in one ml of 
normal human plasma.  
 
On demand treatment 
The calculation of the required dose of factor IX is based on the empirical finding that 1 International 
Unit (IU) factor IX per kg body weight is expected to increase the circulating level of factor IX by an 
average of 1.3 IU/dl (1.3 % of normal) in patients ≥ 12 years of age and by 1.0 IU/dl (1.0 % of normal) 
in patients < 12 years of age. The required dose is determined using the following formulae: 
 

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


48 

Required dose (IU) = body weight (kg) x desired factor IX rise (% of normal or IU/dl) x {reciprocal of 
observed recovery (IU/kg per IU/dl)} 
 
Expected factor IX rise (IU/dl or % of normal) = Dose (IU) x Recovery (IU/dl per IU/kg)/body weight 
(kg) 
 
The amount to be administered and the frequency of administration should always be oriented to the 
clinical effectiveness in the individual case. 
 
Patients < 12 years of age 
For an incremental recovery of 1 IU/dl per 1 IU/kg, the dose is calculated as follows: 
Dose (IU) = body weight (kg) x desired factor IX increase (IU/dl) x 1 dl/kg 
 
Example  
1. A peak level of 50 % of normal is required in a 20 kg patient with severe haemophilia B. The 

appropriate dose would be 20 kg x 50 IU/dl x 1 dl/kg = 1000 IUs. 
 
2. A dose of 1000 IUs of IDELVION, administered to a 25 kg patient, should be expected to result 

in a peak post-injection factor IX increase of 1000 IUs/25 kg x 1.0 (IU/dl per IU/kg) = 40 IU/dl 
(40 % of normal). 

 
Patients ≥ 12 years of age 
For an incremental recovery of 1.3 IU/dl per 1 IU/kg, the dose is calculated as follows:  
Dose (IU) = body weight (kg) x desired factor IX increase (IU/dl) x 0.77 dl/kg 
 
Example  
3. A peak level of 50 % of normal is required in a 80 kg patient with severe haemophilia B.  The 

appropriate dose would be 80 kg x 50 IU/dl x 0.77 dl/kg = 3080 IUs. 
 
4. A dose of 2000 IUs of IDELVION, administered to a 80 kg patient, should be expected to result 

in a peak post-injection factor IX increase of 2000 IUs x 1.3 (IU/dl per IU/kg) 
/80 kg = 32.5 IU/dl (32.5 % of normal). 

 
In the case of the following haemorrhagic events, the factor IX activity should not fall below the given 
plasma activity level (in % of normal or in IU/dl) in the corresponding period. The following table can 
be used to guide dosing in bleeding episodes and surgery: 

Degree of Haemorrhage /  
Type of surgical procedure  

Factor IX level 
required (%) (IU/dl) 

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

Haemorrhage  
Minor or moderate Haemarthrosis, 
muscle bleeding (except iliopsoas) 
or oral bleeding  

30 - 60 Single dose should be 
sufficient for majority of 
bleeds. Maintenance dose 
after 24 – 72 hours if there is 
further evidence of bleeding.  

Major haemorrhage 
Life threatening haemorrhages, 
deep muscle bleeding including 
iliopsoas  

60 - 100 Repeat every 24 – 72 hours 
for the first week, and then 
maintenance dose weekly 
until bleeding stops and 
healing is achieved. 

Minor surgery  
Including uncomplicated tooth 
extraction  

50 – 80 (initial level) Single dose may be sufficient 
for a majority of minor 
surgeries. If needed, 
maintenance dose can be 
provided after 24 – 72 hours 
until bleeding stops and 
healing is achieved.  



49 

Major surgery  60 - 100 
(initial level) 

Repeat every 24 – 72 hours 
for the first week, and then 
maintenance dose 1 – 2 times 
per week until bleeding stops 
and healing is achieved. 

 
Prophylaxis  
For long term prophylaxis against bleeding in patients with severe hemophilia B, the usual doses are 
35 to 50 IU/kg once weekly. 
Some patients who are well-controlled on a once-weekly regimen might be treated with up to 75 IU/kg 
on an interval of 10 or 14 days. For patients >18 years, further extension of the treatment interval may 
be considered (see section 5.1). 
 
In some cases, especially in younger patients, shorter dosage intervals or higher doses may be 
necessary. 
 
After a bleeding episode during prophylaxis, patients should maintain their prophylaxis regimen as 
closely as possible, with 2 doses of IDELVION being administered at least 24 hours apart but longer 
as deemed suitable for the patient. 
 
Paediatric population  
For routine prophylaxis , the recommended dose regimen is 35 to 50 IU/kg once weekly (see sections 
5.1 and 5.2). 
 
 
Special warnings and precautions for use 
 
Inhibitors  
After repeated treatment with human coagulation factor IX products, patients should be monitored for 
the development of neutralising antibodies (inhibitors) that should be quantified in Bethesda Units (BU) 
using appropriate biological testing.  
 
There have been reports in the literature showing a correlation between the occurrence of a factor IX 
inhibitor and allergic reactions. Therefore, patients experiencing allergic reactions should be evaluated 
for the presence of an inhibitor. It should be noted that patients with factor IX inhibitors may be at an 
increased risk of anaphylaxis with subsequent challenge with factor IX.  
 
Treatment monitoring 
During the course of treatment, appropriate determination of factor IX levels is advised to guide the 
dose to be administered and the frequency of repeated infusions. Individual patients may vary in their 
responses to factor IX, 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 IX activity) is indispensable. 
 
When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining 
Factor IX activity in patients’ blood samples, plasma factor IX activity results can be significantly 
affected by both the type of aPTT reagent and the reference standard used in the assay. Measurement 
with a one-stage clotting assay using a kaolin based aPTT reagent or Actin FS aPTT reagent will 
likely result in an underestimation of activity level. This is of importance particularly when changing 
the laboratory and/or reagents used in the assay. 


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