Alprolix

1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of new 
safety information. Healthcare professionals are asked to report any suspected adverse reactions. See 
section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ALPROLIX 250 IU powder and solvent for solution for injection 
 
ALPROLIX 500 IU powder and solvent for solution for injection 
 
ALPROLIX 1000 IU powder and solvent for solution for injection 
 
ALPROLIX 2000 IU powder and solvent for solution for injection 
 
ALPROLIX 3000 IU powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
ALPROLIX 250 IU powder and solvent for solution for injection 
Each vial contains nominally 250 IU eftrenonacog alfa. After reconstitution, each mL of solution for 
injection contains approximately 50 IU eftrenonacog alfa.  
 
ALPROLIX 500 IU powder and solvent for solution for injection 
Each vial contains nominally 500 IU eftrenonacog alfa. After reconstitution, each mL of solution for 
injection contains approximately 100 IU eftrenonacog alfa. 
 
ALPROLIX 1000 IU powder and solvent for solution for injection 
Each vial contains nominally 1000 IU eftrenonacog alfa. After reconstitution, each mL of solution for 
injection contains approximately 200 IU eftrenonacog alfa.  
 
ALPROLIX 2000 IU powder and solvent for solution for injection 
Each vial contains nominally 2000 IU eftrenonacog alfa. After reconstitution, each mL of solution for 
injection contains approximately 400 IU eftrenonacog alfa. 
 
ALPROLIX 3000 IU powder and solvent for solution for injection 
Each vial contains nominally 3000 IU eftrenonacog alfa. After reconstitution, each mL of solution for 
injection contains approximately 600 IU eftrenonacog alfa. 
 
The potency (International Units) is determined using the European Pharmacopoeia one stage clotting test 
against an in-house standard that is referenced to the WHO factor IX standard. The specific activity of 
ALPROLIX is 55-84 IU/mg protein. 
 
Eftrenonacog alfa (recombinant human coagulation factor IX, Fc fusion protein (rFIXFc)) has 867 amino 
acids. It is a high purity factor product produced by recombinant DNA technology in a human embryonic 
kidney (HEK) cell line, without the addition of any exogenous human- or animal-derived protein in the cell 
culture, purification or final formulation. 
 
Excipient with known effect: 0.3 mmol (6.4 mg) sodium per vial. 
 
For the full list of excipients, see section 6.1. 
 
 



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3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection. 
 
Powder: lyophilised, white to off-white powder or cake. 
Solvent: the solution is clear to colourless. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment and prophylaxis of bleeding in patients with haemophilia B (congenital factor IX deficiency). 
 
ALPROLIX 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. 
 
Previously untreated patients 
The safety and efficacy of ALPROLIX in previously untreated patients have not yet been established. No 
data are available. 
 
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 injections. Individual patients may vary in their response 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. This is of importance particularly when 
changing the laboratory and/or reagents used in the assay.  
Measurements with a one-stage clotting assay utilising a kaolin-based aPTT reagent will likely result in an 
underestimation of activity level. 
 
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 recombinant factor IX Fc 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 recombinant factor IX Fc 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 recombinant factor IX Fc is based on the empirical finding that 1 
International Unit (IU) factor IX per kg body weight raises the plasma factor IX activity by 1% of normal 
activity (IU/dL). The required dose is determined using the following formula:  
 



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Required units = body weight (kg) x desired factor IX rise (%) (IU/dL) x {reciprocal of observed recovery 
(IU/kg per IU/dL)} 
 
The amount to be administered and the frequency of administration should always be oriented to the clinical 
effectiveness in the individual case. If a repeat dose is required to control the bleed, the prolonged half-life of 
ALPROLIX should be taken into account (see section 5.2). The time to peak activity is not expected to be 
delayed. 
 
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 IU/dL) in the corresponding period. Table 1 can be used to guide 
dosing in bleeding episodes and surgery: 
 
Table 1: Guide to ALPROLIX dosing for treatment of bleeding episodes and surgery 

 
1 In some patients and circumstances the dosing interval can be prolonged up to 48 hours (see section 5.2 for pharmacokinetic data). 
 
Prophylaxis  
For long term prophylaxis against bleeding, the recommended starting regimens are either: 
• 50 IU/kg once weekly, adjust dose based on individual response or 
• 100 IU/kg once every 10 days, adjust interval based on individual response. Some patients who are 

well-controlled on a once every 10 days regimen might be treated on an interval of 14 days or longer. 
 
The highest recommended dose for prophylaxis is 100 IU/kg 
 
Elderly population  
There is limited experience in patients ≥ 65 years. 
 
Paediatric population 
For children below the age of 12 years, higher or more frequent doses may be required and the recommended 
starting dose is 50-60 IU/kg every 7 days. For adolescents of 12 years of age and above, the dose 
recommendations are the same as for adults. See sections 5.1 and 5.2. 
The highest recommended dose for prophylaxis is 100 IU/kg 
 

Degree of haemorrhage 
/ Type of surgical 
procedure 

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

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

Haemorrhage   
Early haemarthrosis, 
muscle bleeding or oral 
bleeding 

20-40 Repeat injection every 48 hours, until the 
bleeding episode as indicated by pain is 
resolved or healing is achieved. 
 

More extensive 
haemarthrosis, muscle 
bleeding or haematoma 

30-60 Repeat injection every 24 to 48 hours until 
pain and acute disability are resolved. 
 

Life threatening 
haemorrhages 

60-100 Repeat injection every 8 to 24 hours until 
threat is resolved. 
 

Surgery   
Minor surgery including 
tooth extraction 

30-60 Repeat injection after 24 hours, as needed until 
healing is achieved1. 
 

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

Repeat injection every 8 to 24 hours as 
necessary until adequate wound healing, then 
therapy at least for another 7 days to maintain 
a factor IX activity of 30% to 60% (IU/dL). 
 



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Method of administration  
Intravenous use.  
 
In case of self-administration or administration by a caregiver appropriate training is needed. 
 
ALPROLIX should be injected intravenously over several minutes. The rate of administration should be 
determined by the patient’s comfort level and should not exceed 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 (recombinant human coagulation factor IX, and/or Fc domain) or to 
any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Hypersensitivity 
Allergic type hypersensitivity reactions have been reported with ALPROLIX. 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 
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 administrations 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 with factor IX products, 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 disseminated intravascular coagulation (DIC). 
The benefit of treatment with ALPROLIX in these situations 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. 
 



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Recording of batch number 
It is strongly recommended that every time that ALPROLIX is administered to a patient, the name and batch 
number of the product are recorded in order to maintain a link between the patient and the batch of the 
medicinal product. 
 
Paediatric population 
The listed warnings and precautions apply both to adults and children. 
 
Excipient related considerations 
This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially “sodium-
free”.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interactions of ALPROLIX with other medicinal products have been reported. No interaction studies 
have been performed. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy and breast-feeding 
Animal reproduction studies have not been conducted with ALPROLIX. A placental transfer study in mice 
was conducted (see section 5.3). 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 breast-feeding only if clearly indicated. 
 
Fertility 
There are no fertility data available. No fertility studies have been conducted in animals with ALPROLIX. 
 
4.7 Effects on ability to drive and use machines 
 
ALPROLIX 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 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. 
 
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. 
 
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 thromboembolic 
complications. 
 
Tabulated list of adverse reactions 
The frequencies in the table below were observed in a total of 153 patients with severe haemophilia B in 
phase III clinical studies and an extension study. Adverse events were monitored for a total of 561 subject-



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years. The total number of exposure days was 26,106 with a median of 165 (range 1-528) exposure days per 
subject. 
 
Table 2 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. 
 
Table 2: Adverse reactions reported for ALPROLIX in clinical trials 
MedDRA System Organ Class Adverse reactions Frequency category 
Metabolism and nutrition disorders Decreased appetite  Uncommon 
Nervous system disorders Headache 

Dizziness 
Dysgeusia 

 Common 
 Uncommon 
 Uncommon 

Cardiac disorders Palpitations  Uncommon 
Vascular disorders Hypotension  Uncommon 
Gastrointestinal disorders Paresthesia oral 

Breath odour 
 Common 
 Uncommon 

Renal and urinary disorders Obstructive uropathy 
Haematuria 
Renal colic 

 Common 
 Uncommon 
 Uncommon 

General disorders and administration site conditions Fatigue 
Infusion site pain  

 Uncommon 
 Uncommon 

 
Post Marketing Experience 
In post-marketing experience, FIX inhibitor development and hypersensitivity (including anaphylaxis) have 
been observed. 
 
Paediatric population  
Frequency, type and severity of adverse reactions in children are expected to be similar as in adults. For 
extent and age characterisation of the safety database in children see section 5.1. 
 
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 
 
The effects of higher than recommended doses of ALPROLIX have not been characterised. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor IX, ATC code: B02BD04 
 
Mechanism of action 
Factor IX is a single chain glycoprotein with a molecular mass of about 68,000 Dalton. It is a vitamin-K 
dependent coagulation factor. Factor IX is activated by factor XIa in the intrinsic coagulation pathway and 
by the factor VII/tissue factor complex in the extrinsic pathway. Activated factor IX, in combination with 

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


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activated factor VIII, activates factor X. Activated factor X converts prothrombin into thrombin. Thrombin 
then converts fibrinogen into fibrin and a clot is formed. Haemophilia B is an X-linked hereditary disorder of 
blood coagulation due to decreased levels of factor IX and results in bleeding into joints, muscles or internal 
organs, either spontaneously or as a result of accidental or surgical trauma. By replacement therapy the 
plasma level of factor IX is increased thereby enabling a temporary correction of the factor deficiency and 
correction of the bleeding tendencies.  
 
ALPROLIX (eftrenonacog alfa) is a long-acting, fully recombinant, fusion protein comprising human 
coagulation factor IX covalently linked to the Fc domain of human immunoglobulin G1, and produced by 
recombinant DNA technology.  
 
The Fc region of human immunoglobulin G1 binds with the neonatal Fc receptor. This receptor is expressed 
throughout life as part of a naturally occurring pathway that protects immunoglobulins from lysosomal 
degradation by cycling these proteins back into circulation, resulting in their long plasma half-life. 
 
Clinical efficacy and safety 
The safety, efficacy, and pharmacokinetics of ALPROLIX were evaluated in 2 multinational, open-label, 
pivotal studies; a phase 3 study in adults and adolescents, referred to as study I and a phase 3 paediatric 
study, referred to as study II (see Paediatric population).  
 
Study I compared the efficacy of each of 2 prophylactic treatment regimens (fixed weekly interval with 
dosing of 50 IU/kg, and individualised interval with 100 IU/kg starting every 10 days) to on demand 
treatment. The study enrolled a total of 123 previously treated male patients (12 to 71 years of age) with 
severe haemophilia B (≤2% endogenous FIX activity). All patients received treatment with ALPROLIX and 
were followed for up to 77 weeks.  
 
Out of 123 subjects who completed Study I, 93 were enrolled in Study III (extension study) with median 
total follow-up time of 6.5 years. 
 
Prophylaxis fixed weekly and individualised intervals:  
Median weekly dose for subjects in the fixed weekly arm was 45.17 IU/kg (interquartile range (IQR) 38.1-
53.7) in Study I. The corresponding median Annualised Bleeding Rates (ABR) in subjects evaluable for 
efficacy were 2.95 (IQR: 1.01-4.35) and remained similar throughout Study III (1.85 (IQR: 0.76-4.0)). 
Subjects had a median of 0.38 (IQR: 0.00-1.43) spontaneous joint bleeds in Study III. 
 
For subjects in the individualised interval arm, the median dosing interval was 12.53 days (IQR: 10.4-13.4) 
in Study I. The corresponding median ABR was 1.38 (IQR: 0.00-3.43) and remained similar throughout 
Study III (1.85 (IQR: 0.76-4.0)).  
Dosing intervals and factor consumption remained similar in Study III (extension study) compared to Study I 
for both prophylactic regimens.  
 
No bleeding episodes were experienced in 42% of subjects while on individualised prophylaxis and in 23% 
of subjects while on weekly prophylaxis. There was a lower proportion of subjects in individualised interval 
prophylaxis with ≥1 target joint at baseline than in weekly prophylaxis (27.6% and 57.1%, respectively). 
Of note, ABR is not comparable between different factor concentrates and between different clinical studies. 
 
Treatment of bleeding: Of the 636 bleeding events observed during study I, 90.4 % were controlled with 
1 injection and overall 97.3% with 2 or fewer injections. The median average dose per injection to treat a 
bleeding episode was 46.07 (IQR: 32.86-57.03) IU/kg. The median overall dose to treat a bleeding episode 
was 51.47 IU/kg (IQR: 35.21-61.73) in the weekly prophylaxis arm, 49.62 IU/kg (IQR: 35.71-94.82) in the 
individualised interval prophylaxis arm and 46.58 IU/kg (IQR: 33. 33-59.41) in the on demand treatment 
arm. 
 
Perioperative management (surgical prophylaxis): 
A total of 35 major surgical procedures were performed and assessed in 22 subjects (21 adults and 
adolescents, and 1 paediatric patient <12 years of age) in Study I and Study III. Of the 35 major surgeries, 28 
surgeries (80.0%) required a single pre-operative dose to maintain haemostasis during surgery. The median 



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average dose per injection to maintain hemostasis during surgery was 94.7 IU/kg (range: 49 to 152 IU/kg). 
The total dose on the day of surgery ranged from 49 to 341 IU/kg and the total dose in the 14 day 
perioperative period ranged from 60 to 1947 IU/kg. 
 
The haemostatic response was rated as excellent or good in 100% of major surgeries. 
 
Paediatric population 
 
Study II enrolled a total of 30 previously treated male paediatric patients with severe hemophilia B (≤2% 
endogenous FIX activity). Patients were less than 12 years of age (15 were <6 years of age and 15 were 6 to 
<12 years of age). All patients received treatment with ALPROLIX and were followed for up to 52 weeks. 
 
All of the 30 patients were treated with ALPROLIX on a prophylactic dosing regimen starting with 
50-60 IU/kg every 7 days, with adjustment of dose to a maximum of 100 IU/kg and dosing interval to a 
minimum of once weekly and a maximum of twice weekly. Out of 30 patients having completed Study II, 27 
enrolled to Study III (extension study). The median time on Study II+III was 2.88 years and median number 
of exposure days was 166. 
 
Prophylaxis Individualised Regimen:  
The median average weekly dose of ALPROLIX was 59.40 IU/kg (interquartile range, 52.95 to 64.78 IU/kg) 
for subjects <6 years of age and 57.78 IU/kg (interquartile range, 51.67 to 65.01 IU/kg) for subjects 6 to 
<12 years of age. The median dosing interval overall was 6.99 day (interquartile range, 6.94 to 7.03) with no 
difference in the median dosing interval between age cohorts. With the exception of one patient whose last 
prescribed dose was 100 IU/kg every 5 days, the other 29 patients last prescribed doses were up to 70 IU/kg 
every 7 days. No bleeding episodes were experienced in 33% of paediatric subjects. Dosing intervals and 
factor consumption remained similar in Study III compared to Study II. 
 
Median annualised bleeding rates in subjects <12 years of age evaluable for efficacy were 1.97 (interquartile 
range 0.00-3.13) in Study II and remained similar throughout Study III (extension study). 
 
Treatment of bleeding episodes: Of the 60 bleeding events observed during study II, 75% were controlled 
with 1 injection, and overall 91.7% of bleeding episodes were controlled with 2 or fewer injections. The 
median average dose per injection to treat a bleeding episode was 63.51 (interquartile range, 48.92-
99.44) IU/kg. The median overall dose to treat a bleeding episode was 68.22 IU/kg (interquartile range, 
50.89-126.19). 
 
5.2 Pharmacokinetic properties 
 
All pharmacokinetic studies with ALPROLIX were conducted in previously treated patients with severe 
haemophilia B. Data presented in this section were obtained by one-stage clotting assay with a silica-based 
aPTT reagent calibrated against factor IX plasma standards.  
 
Pharmacokinetic properties were evaluated in 22 subjects (≥19 years) receiving ALPROLIX (rFIXFc). 
Following a washout period of at least 120 hours (5 days), the subjects received a single dose of 50 IU/kg of 
ALPROLIX. Pharmacokinetic samples were collected pre-dose and then subsequently at 11 time points up to 
240 hours (10 days) post-dose. Pharmacokinetic parameters of the non-compartmental analysis after 
50 IU/kg dose of ALPROLIX are presented in Table 3. 
 
Table 3: Pharmacokinetic parameters of ALPROLIX (50 IU/kg dose) 

Pharmacokinetic parameters1 
ALPROLIX  

(95% CI) 
N=22 

Incremental Recovery (IU/dL per IU/kg) 0.92 (0.77-1.10) 
AUC/Dose 

(IU*h/dL per IU/kg) 
31.58 

(28.46-35.05) 

Cmax (IU/dL) 
46.10 

(38.56-55.11) 



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CL (mL/h/kg) 3.17 (2.85-3.51) 

t½ (h) 
77.60 

(70.05-85.95) 

t½α (h)2 
5.03 

(3.20-7.89) 

t½β (h)2 
82.12 

(71.39-94.46) 

MRT (h) 95.82 (88.44-106.21) 

Vss (mL/kg) 
303.4 

(275.1-334.6) 

Time to 1% (days)2 11.22  (10.20-12.35) 
1 Pharmacokinetic parameters are presented in Geometric Mean (95% CI)  
2 These pharmacokinetic parameters obtained from the compartmental analysis 
Abbreviations: CI = confidence interval; Cmax= maximum activity; AUC = area under the FIX activity time curve; t1/2 = terminal half-life; t½α = 
distribution half-life; t½β = elimination half-life; CL = clearance; Vss = volume of distribution at steady-state; MRT = mean residence time. 
 
The elimination half-life of ALPROLIX (82 hours) is influenced by the Fc region, which in animal models 
was shown to be mediated by neonatal Fc receptor cycling pathways. 
 
A population pharmacokinetic model was developed based on FIX activity data from 161 subjects of all ages 
(2-76 years of age) weighing between 12.5 kg to 186.7 kg in three clinical studies (12 subjects in a phase 
1/2a study, 123 subjects in study I and 26 subjects in study II). The estimate of CL of ALPROLIX for a 
typical 70 kg adult is 2.30 dL/h and steady-state volume of distribution of ALPROLIX is 194.8 dL, 
respectively. The observed mean (SD) activity time profile following a single dose of ALPROLIX in patients 
with severe haemophilia B is shown below (see Table 4). 
 
Table 4: The Observed Mean (SD) FIX activity [IU/dL] following a single dose of ALPROLIX1 for patients 

≥ 12 years of Age 
Dose 

 

10 mins  1h  3h 6h 24h 48h 96h 144h 168h 192h 240 h 288 h 

50 

52.9 
(
3
0
.
6
) 

34.5 
(7.3) 

28.7 
(6.7) 

25.1 
(5.1) 

15.1 
(3.9) 

9.7 
(3.0) 

5.0 
(1.6) 

3.4 
1.1) 

3.2 
(1.9) 

2.6 
(1.0) 

2.1 
(0.9) NA 

100 112 (24) NA 
77.1 

(12.8) NA 
36.7 
(8.0) 

21.8  
(4.8) 

10.1 
(2.6) NA 

4.81 
(1.67) NA 

2.86 
(0.98) 

2.30 
(0.94) 

1 See section 4.2; NA: Not available 
 
Paediatric population 
Pharmacokinetic parameters of ALPROLIX were determined for adolescents in study I (pharmacokinetic 
sampling was conducted pre-dose followed by assessment at multiple time points up to 336 hours (14 days) 
post-dose) and for children in study II (pharmacokinetic sampling was conducted pre-dose followed by 
assessment at 7 time points up to 168 hours (7 days) post-dose). Table 5 presents the pharmacokinetic 
parameters calculated from the paediatric data of 35 subjects less than 18 years of age.  
 



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Table 5: Comparison of PK Parameters of ALPROLIX (rFIXFc) by Age Category 

PK Parameters1 

Study II Study I 
<6 years 

(2, 4) 
6 to <12 years 

(6, 10) 
12 to <18 years 

(12, 17) 
N = 11 N = 13 N = 11 

IR 
(IU/dL per IU/kg) 

0.5989 
(0.5152, 0.6752) 

0.7170 
(0.6115, 0.8407) 

0.8470 
(0.6767, 1.0600) 

AUC/Dose 
(IU*h/dL per IU/kg) 

22.71 
(20.32, 25.38) 

28.53 
(24.47, 33.27) 

29.50 
(25.13, 34.63) 

t½ (h) 
66.49 

(55.86, 79.14) 
70.34 

(60.95, 81.17) 
82.22 

(72.30, 93.50) 

MRT (h) 83.65 (71.76, 97.51) 
82.46 

(72.65, 93.60) 
93.46 

(81.77, 106.81) 

CL (mL/h/kg) 4.365 (3.901, 4.885) 
3.505 

(3.006, 4.087) 
3.390 

(2.888, 3.979) 
Vss (mL/kg) 

365.1 
(316.2, 421.6) 

289.0 
(236.7, 352.9) 

316.8 
(267.4, 375.5) 

1PK parameters derived from noncompartmental analysis are presented in Geometric Mean (95% CI)  
Abbreviations: CI = confidence interval; IR = incremental recovery; AUC = area under the FIX activity time curve; t1/2 = terminal 
half-life; MRT = mean residence time; CL = clearance; Vss = volume of distribution at steady-state 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on thrombogenicity test in rabbits (Wessler 
stasis model) and repeated dose toxicity studies (which included assessment of local toxicity, male 
reproductive organs and electrocardiographic parameters) in rats and monkeys. Studies to investigate 
genotoxicity, carcinogenicity, toxicity to reproduction or embryo-foetal development have not been 
conducted. In a placental transfer study, ALPROLIX has been shown to cross the placenta in small amounts 
in mice. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder 
Sucrose 
L-histidine 
Mannitol 
Polysorbate 20 
Sodium hydroxide (for pH adjustment) 
Hydrochloric acid (for pH adjustment) 
 
Solvent 
Sodium chloride  
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.  
 
Only the provided infusion set should be used because treatment failure can occur as a consequence of 
coagulation factor IX adsorption to the internal surfaces of some injection equipment. 
 



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6.3 Shelf life 
 
Unopened vial 
4 years 
 
During the shelf-life, the product may be stored at room temperature (up to 30°C) for a single period not 
exceeding 6 months. The date that the product is removed from refrigeration should be recorded on the 
carton. After storage at room temperature, the product may not be returned to the refrigerator. The product 
should not be used beyond the expiry date printed on the vial or six months after removing the carton from 
refrigeration, whichever is earlier. 
 
After reconstitution 
Chemical and physical stability has been demonstrated for 6 hours when stored at room temperature (up to 
30°C). If the product is not used within 6 hours, it must be discarded. From a microbiological point of view, 
the product should be used immediately after reconstitution. If not used immediately, in-use storage times 
and conditions prior to use are the responsibility of the user. Protect product from direct sunlight. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C - 8°C). Do not freeze. Keep the vial 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 and special equipment for use, administration  
 
Each pack contains: 
- powder in a type 1 glass vial with a chlorobutyl rubber stopper 
- 5 mL solvent in a type 1 glass pre-filled syringe with a bromobutyl rubber plunger stopper 
- a plunger rod 
- a sterile vial adapter for reconstitution 
- a sterile infusion set 
- alcohol swab(s) 
- plaster(s) 
- gauze pad(s). 
 
Pack size of 1. 
 
6.6 Special precautions for disposal and other handling 
 
The powder for injection in each vial must be reconstituted with the supplied solvent (sodium chloride 
solution) from the pre-filled syringe using the sterile vial adapter for reconstitution.  
 
The vial should be gently swirled until all of the powder is dissolved.  
 
Please see package leaflet, for additional information on reconstitution and administration. 
 
The reconstituted solution should be clear to slightly opalescent and colourless. Reconstituted medicinal 
product should be inspected visually for particulate matter and discoloration prior to administration. Do not 
use solutions that are cloudy or have deposits.  
 
This product is for single use only. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 



13 

7. MARKETING AUTHORISATION HOLDER 
 
Swedish Orphan Biovitrum AB (publ) 
SE-112 76 Stockholm 
Sweden 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1098/001 
EU/1/16/1098/002 
EU/1/16/1098/003 
EU/1/16/1098/004 
EU/1/16/1098/005 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 12 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/


14 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

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

 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND 

USE 
 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION 

 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE 

SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 



15 

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

 
Name and address of the manufacturer(s) of the biological active substance  
 
Biogen Inc. 
5000 Davis Drive 
Research Triangle Park 
North Carolina 
27709-4627 
United States 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Swedish Orphan Biovitrum AB (publ) 
Strandbergsgatan 49 
11276 Stockholm 
Sweden 
 
 
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.  



16 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



17 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



18 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
ALPROLIX 250 IU powder and solvent for solution for injection 
 
ALPROLIX 500 IU powder and solvent for solution for injection 
 
ALPROLIX 1000 IU powder and solvent for solution for injection 
 
ALPROLIX 2000 IU powder and solvent for solution for injection 
 
ALPROLIX 3000 IU powder and solvent for solution for injection 
 
eftrenonacog alfa  
recombinant coagulation factor IX, Fc fusion protein 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Powder: 250 IU eftrenonacog alfa (approx. 50 IU/mL after reconstitution), 
 
Powder: 500 IU eftrenonacog alfa (approx. 100 IU/mL after reconstitution) 
 
Powder: 1000 IU eftrenonacog alfa (approx. 200 IU/mL after reconstitution) 
 
Powder: 2000 IU eftrenonacog alfa (approx. 400 IU/mL after reconstitution) 
 
Powder: 3000 IU eftrenonacog alfa (approx. 600 IU/mL after reconstitution) 
 
 
3. LIST OF EXCIPIENTS 
 
Powder:  
sucrose, L-histidine, mannitol, polysorbate 20, sodium hydroxide, hydrochloric acid 
 
Solvent:  
sodium chloride, water for injections 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
powder and solvent for solution for injection 
 
Content: 1 powder vial, 5 mL solvent in pre-filled syringe, 1 plunger rod, 1 vial adapter, 1 infusion set, 2 
alcohol swabs, 2 plasters, 1 gauze 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Intravenous use, after reconstitution.  
Read the package leaflet before use. 



19 

 
An instructional video on how to prepare and administer ALPROLIX is available by scanning the QR code 
with a smartphone or via the website 
 
QR code to be included + http://www.alprolix-instructions.com  
 
 
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 6 hours after reconstitution. 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Keep the vial in the outer carton in order to protect from light. 
Store in a refrigerator. 
Do not freeze. 
Can be stored at room temperature (up to 30°C) for a single period up to 6 months. Must not be returned to 
refrigerator after storage at room temperature. 
Date removed from refrigerator: 
 
 
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 
 
Swedish Orphan Biovitrum AB (publ) 
SE-112 76 Stockholm 
Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/16/1098/001 
EU/1/16/1098/002 
EU/1/16/1098/003 
EU/1/16/1098/004 
EU/1/16/1098/005 
 
 

http://www.alprolix-instructions.com/


20 

13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
ALPROLIX 250  
 
ALPROLIX 500  
 
ALPROLIX 1000  
 
ALPROLIX 2000  
 
ALPROLIX 3000  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: {number} 
SN: {number} 
NN: {number} 
 
 



21 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
VIAL LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
ALPROLIX 250 IU powder for injection 
 
ALPROLIX 500 IU powder for injection 
 
ALPROLIX 1000 IU powder for injection 
 
ALPROLIX 2000 IU powder for injection 
 
ALPROLIX 3000 IU powder for injection 
 
eftrenonacog alfa 
recombinant coagulation factor IX 
IV 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
250 IU 
 
500 IU 
 
1000 IU 
 
2000 IU 
 
3000 IU 
 
 
6. OTHER 
 



22 

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



23 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



24 

Package leaflet: Information for the user 
 

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

 
eftrenonacog alfa recombinant coagulation factor IX, Fc fusion protein  

 
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, 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 ALPROLIX is and what it is used for  
2. What you need to know before you use ALPROLIX 
3. How to use ALPROLIX  
4. Possible side effects  
5. How to store ALPROLIX 
6. Contents of the pack and other information 
7. Instructions for preparation and administration  
 
 
1. What ALPROLIX is and what it is used for 
 
ALPROLIX contains the active substance eftrenonacog alfa, recombinant coagulation factor IX, Fc fusion 
protein. Factor IX is a protein produced naturally in the body necessary for the blood to form clots and stop 
bleeding. 
 
ALPROLIX is a medicine used for the treatment and prevention of bleeding in all age groups of patients 
with haemophilia B (inherited bleeding disorder caused by factor IX deficiency). 
 
ALPROLIX is prepared by recombinant technology without addition of any human- or animal-derived 
components in the manufacturing process.  
 
How ALPROLIX works 
In patients with haemophilia B, factor IX is missing or not working properly. ALPROLIX is used to replace 
the missing or deficient factor IX. ALPROLIX increases factor IX level in the blood and temporarily corrects 
the bleeding tendency. The Fc fusion protein in ALPROLIX increases the length of time that the medicine 
works. 
 
 
2. What you need to know before you use ALPROLIX  
 
Do not use ALPROLIX: 
• if you are allergic to eftrenonacog alfa or any other ingredients of this medicine (listed in section 6). 



25 

 
Warnings and precautions  
Talk to your doctor, pharmacist or nurse before using ALPROLIX. 
 
• There is a small chance that you may experience an anaphylactic reaction (a severe, sudden allergic 

reaction) to ALPROLIX. Signs of allergic reactions may include, generalised itching, hives, tightness 
of the chest, difficulty breathing and low blood pressure. If any of these symptoms occur, stop the 
injection immediately and contact your doctor. 

 
• Talk to your doctor if you think that your bleeding is not being controlled with the dose you receive, as 

there can be several reasons for this. For example, the formation of antibodies (also known as 
inhibitors) to factor IX is a known complication that can occur during the treatment of haemophilia B. 
The antibodies prevent the treatment from working properly. This would be checked by your doctor. 
Do not increase the total dose of ALPROLIX to control your bleed without talking to your doctor.  

 
Patients with a factor IX inhibitor may be at an increased risk of anaphylaxis during future treatment with 
factor IX. Therefore, if you experience allergic reactions such as those described above, you should be tested 
for the presence of an inhibitor.  
 
Factor IX products may increase the risk of unwanted blood clots in your body, especially if you have risk 
factors for developing blood clots. Symptoms of a possible unwanted blood clot may include: pain and/or 
tenderness along a vein, unexpected swelling of an arm or leg or sudden shortness of breath or difficulty 
breathing. 
 
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 blood clots should be considered. 
 
Documentation 
It is strongly recommended that every time ALPROLIX is given, the name and batch number of the product 
are recorded. 
 
Other medicines and ALPROLIX 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. 
 
Pregnancy and breast-feeding  
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your 
doctor or pharmacist for advice before taking this medicine. 
 
Driving and using machines  
ALPROLIX has no influence on the ability to drive and use machines. 
 
ALPROLIX contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per vial after preparation, that is to say essentially 
“sodium free”.. 
 
 
3. How to use ALPROLIX 
 
Treatment with ALPROLIX will be started by a doctor who is experienced in the care of patients with 
haemophilia. Always use this medicine exactly as your doctor has told you (see section 7). Check with your 
doctor, pharmacist or nurse if you are not sure. 
 
ALPROLIX is given as an injection into a vein. You or somebody else may administer ALPROLIX after 
receiving adequate training. Your doctor will decide the dose of ALPROLIX (in International Units or “IU”) 
you will receive. The dose will depend on your individual needs for replacement factor IX therapy and on 



26 

whether it is used for prevention or treatment of bleeding. Talk to your doctor if you think that your bleeding 
is not being controlled with the dose you receive. 
 
How often you need an injection will depend on how well ALPROLIX is working for you. Your doctor will 
perform appropriate laboratory tests to make sure that you have adequate factor IX levels in your blood.  
 
Treatment of bleeding  
The dose of ALPROLIX is calculated depending on your body weight and the factor IX levels to be 
achieved. The target factor IX levels will depend on the severity and location of the bleeding. 
 
Prevention of bleeding  
If you are using ALPROLIX to prevent bleeding, your doctor will calculate the dose for you.  
 
The usual dose of ALPROLIX is 50 IU per kg of body weight, given once a week or 100 IU per kg of body 
weight, given once every 10 days. The dose or interval may be adjusted by your doctor. In some cases, 
especially in younger patients, shorter dosing intervals or higher doses may be necessary. 
 
Use in children and adolescents 
ALPROLIX can be used in children and adolescents of all ages. In children below the age of 12 years, higher 
doses or more frequent injections may be needed and the usual dose is 50 to 60 IU per kg of body weight, 
given once every 7 days.  
 
If you use more ALPROLIX than you should 
Tell your doctor as soon as possible. You should always use ALPROLIX exactly as your doctor has told you, 
check with your doctor, pharmacist or nurse if you are not sure.  
 
If you forget to use ALPROLIX 
Do not take a double dose to make up for a forgotten dose. Take your dose as soon as you remember and 
then resume your normal dosing schedule. If you are not sure what to do, ask your doctor, pharmacist or 
nurse.  
 
If you stop using ALPROLIX 
Do not stop using ALPROLIX without consulting your doctor. If you stop using ALPROLIX you may no 
longer be protected against bleeding or a current bleed may not stop. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them.  
 
If severe, sudden allergic reactions (anaphylactic reaction) occur, the injection must be stopped immediately. 
You must contact your doctor immediately if you experience any of the following symptoms of allergic 
reactions: swelling of the face, rash, generalised itching, hives, tightness of the chest, difficulty breathing, 
burning and stinging at the injection site, chills, flushing, headache, general feeling of being unwell, nausea, 
restlessness, fast heartbeat, and low blood pressure. 
 
The following side effects may occur with this medicine. 
 
Common side effects (may affect up to 1 in 10 people): headache, mouth numbness or tingling, pain in 
your side with blood in your urine (obstructive uropathy). 
 
Uncommon side effects (may affect up to 1 in 100 people): dizziness, taste alteration, bad breath, feeling 
tired, pain at the injection site, rapid heartbeat, blood in the urine (haematuria), pain in your side (renal 
colic), low blood pressure, and decreased appetite. 
 



27 

Reporting of side effects 
If you get any side effects, talk to your doctor or 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 ALPROLIX 
 
Keep this medicine out of the sight and reach of children.  
 
Store in a refrigerator (2°C - 8°C). Do not freeze. Store in the original pack in order to protect from light. 
 
Alternatively, ALPROLIX may be stored at room temperature (up to 30°C) for a single period not exceeding 
6 months. Please record on the carton the date that ALPROLIX is removed from the refrigerator and set at 
room temperature. After storage at room temperature, the product must not be put back in the refrigerator.  
 
Do not use this medicine after the expiry date which is stated on the carton and the vial label after “EXP”. 
The expiry date refers to the last day of that month. Do not use this medicine if it has been stored at room 
temperature for longer than 6 months. 
 
Once you have prepared ALPROLIX it should be used right away. If you cannot use the prepared 
ALPROLIX solution immediately, it should be used within 6 hours when stored at room temperature. Do not 
refrigerate the solution after preparation. Protect the solution from direct sunlight. 
 
The prepared solution will be clear to slightly opalescent and colourless. Do not use this medicine if you 
notice that it is cloudy or contains visible particles. 
 
This product is for single use only.  
 
Discard any unused solution appropriately. Do not throw away any medicines via wastewater or household 
waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help 
protect the environment. 
 
 
6. Contents of the pack and other information 
 
What ALPROLIX contains  
Powder: 
• The active substance is eftrenonacog alfa (recombinant coagulation factor IX, Fc fusion protein). Each 

vial of ALPROLIX contains nominally 250, 500, 1000, 2000 or 3000 IU eftrenonacog alfa.  
• The other ingredients are sucrose, L-Histidine, mannitol, polysorbate 20, sodium hydroxide and 

hydrochloric acid. If you are on a controlled sodium diet, see section 2. 
 
Solvent: 
5 mL sodium chloride and water for injections. 
 
What ALPROLIX looks like and contents of the pack 
ALPROLIX is provided as a powder and solvent for solution for injection. The powder is a white to off-
white powder or cake. The solvent provided for preparation of the solution to inject, is a clear, colourless 
solution. After preparation, the solution to inject is clear to slightly opalescent and colourless. 
 
Each pack of ALPROLIX contains 1 powder vial, 5 mL solvent in pre-filled syringe, 1plunger rod, 1vial 
adapter, 1 infusion set, 2 alcohol swabs, 2 plasters and 1 gauze pad 
 

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


28 

Marketing Authorisation Holder and Manufacturer 
Swedish Orphan Biovitrum AB (publ)  
SE-112 76 Stockholm 
Sweden 
Phone: +46 8 697 20 00 
 
 
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. There are also links to other websites about rare diseases and treatments. 
 
Please turn the leaflet over for section 7. Instructions for preparation and administration 
 
 
7. Instructions for preparation and administration 
 
The procedure below describes the preparation and administration of ALPROLIX.  
 
ALPROLIX is administered by intravenous (IV) injection after dissolving the powder for injection with the 
solvent supplied in the pre-filled syringe. ALPROLIX pack contains: 
 
 
 
 
 
 
 
 
 
 
 
 
ALPROLIX should not be mixed with other solutions for injection or infusion. 
 
Wash your hands before opening the pack. 
 
Preparation: 
 
1. Check the name and strength of the package, to make sure it contains the correct medicine. Check the 

expiry date on the ALPROLIX carton. Do not use if the product has expired. 
 
2. If ALPROLIX has been stored in a refrigerator, allow the vial of ALPROLIX (A) and the syringe with 

solvent (B) to reach room temperature before use. Do not use external heat. 
 
3. Place the vial on a clean flat surface. Remove the 

plastic flip-top cap from the ALPROLIX vial 
 
 
 
 
 
 
 
 

 

A) 1 Powder vial 
B) 5 mL Solvent in pre-filled syringe 
C) 1 Plunger rod  
D) 1 Vial adapter 
E) 1 Infusion set 
F) 2 Alcohol swabs 
G) 2 Plasters  
H) 1 Gauze pad 
 

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


29 

4. Wipe the top of the vial with one of the alcohol swabs 
(F) provided in the pack, and allow to air dry. Do not 
touch the top of the vial or allow it to touch anything 
else once wiped.  

 
 
 
 

 

5. Peel back the protective paper lid from the clear plastic vial adapter (D). Do not remove the adapter 
from its protective cap. Do not touch the inside of the vial adapter package. 

 
6. Place the vial on a flat surface. Hold the vial adapter 

in its protective cap and place it squarely over the top 
of the vial. Press down firmly until the adapter snaps 
into place on top of the vial, with the adapter spike 
penetrating the vial stopper. 

 

 
7. Attach the plunger rod (C) to the solvent syringe by 

inserting the tip of the plunger rod into the opening in 
the syringe plunger. Turn the plunger rod firmly 
clockwise until it is securely seated in the syringe 
plunger. 

 

 

8. Break off the white, tamper-resistant, plastic cap from 
the solvent syringe by bending at the perforation cap 
until it snaps off. Set the cap aside by placing it with 
the top down on a flat surface. Do not touch the inside 
of the cap or the syringe tip. 

 

 
 



30 

9. Lift the protective cap away from the adapter and 
discard. 

 

 

10.  Connect the solvent syringe to the vial adapter by 
inserting the tip of the syringe into the adapter 
opening. Firmly push and turn the syringe clockwise 
until it is securely connected. 

 

11. Slowly depress the plunger rod to inject all the solvent 
into the ALPROLIX vial. 

 

12. With the syringe still connected to the adapter and the 
plunger rod pressed down, gently swirl the vial until 
the powder is dissolved.  

 Do not shake. 

 

13. The final solution must be inspected visually before administration. The solution should appear clear 
to slightly opalescent and colourless. Do not use the solution if cloudy or contains visible particles. 

 



31 

14. Ensuring that the syringe plunger rod is still fully 
pressed down, invert the vial. Slowly pull on the 
plunger rod to draw back all the solution through the 
vial adapter into the syringe. 

 

 

15. Detach the syringe from the vial adapter by gently 
pulling and turning the vial counterclockwise. 

 

 

Note: If you use more than one vial of ALPROLIX per injection, each vial should be prepared separately as 
per the previous instructions (steps 1 to 13) and the solvent syringe should be removed, leaving the vial 
adapter in place. A single large luer lock syringe may be used to draw back the prepared contents of each of 
the individual vials. 
 
16. Discard the vial and the adapter. 
 
Note: If the solution is not to be used immediately, the syringe cap should be carefully put back on the 
syringe tip. Do not touch the syringe tip or the inside of the cap. 
 
After preparation, ALPROLIX can be stored at room temperature for up to 6 hours before administration. 
After this time, the prepared ALPROLIX should be discarded. Protect from direct sunlight. 
 
 
Administration (Intravenous Injection): 
 
ALPROLIX should be administered using the infusion set (E) provided in this pack. 
 
1. Open the infusion set package and remove the cap at the end of the 

tubing. Attach the syringe with the prepared ALPROLIX solution 
to the end of the infusion set tubing by turning clockwise. 

 



32 

2. If needed apply a tourniquet and prepare the injection site by wiping the skin well with the other 
alcohol swab provided in the pack. 

 
 
 
 
 
 
 
 
 
 
 
 
3. Remove any air in the infusion set tubing by slowly depressing on the plunger rod until liquid has 

reached the infusion set needle. Do not push the solution through the needle. Remove the clear plastic 
protective cover from the needle. 

 
4. Insert the infusion set needle into a vein as instructed by your doctor or nurse and remove the 

tourniquet. If preferred, you may use one of the plasters (G) provided in the pack to hold the plastic 
wings of the needle in place at the injection site. The prepared product should be injected 
intravenously over several minutes. Your doctor may change your recommended injection rate to make 
it more comfortable for you. 

 
5. After completing the injection and removing the needle, you should 

fold over the needle protector and snap it over the needle. 

 
6. Please safely dispose of the used needle, any unused solution, the syringe and the empty vial in an 

appropriate medical waste container as these materials may hurt others if not disposed of properly. Do 
not reuse equipment. 
 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE 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
	A. LABELLING
	B. PACKAGE LEAFLET