Rixubis

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

 

 



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 1. NAME OF THE MEDICINAL PRODUCT 

 

RIXUBIS 250 IU powder and solvent for solution for injection 

RIXUBIS 500 IU powder and solvent for solution for injection 

RIXUBIS 1000 IU powder and solvent for solution for injection 

RIXUBIS 2000 IU powder and solvent for solution for injection 

RIXUBIS 3000 IU powder and solvent for solution for injection 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

RIXUBIS 250 IU powder and solvent for solution for injection 

One vial contains nominally 250 IU nonacog gamma, recombinant human coagulation factor IX 

(rDNA), corresponding to a concentration of 50 IU/ml after reconstitution with 5 ml solvent. 

 

RIXUBIS 500 IU powder and solvent for solution for injection 

One vial contains nominally 500 IU nonacog gamma, recombinant human coagulation factor IX 

(rDNA), corresponding to a concentration of 100 IU/ml after reconstitution with 5 ml solvent. 

 

RIXUBIS 1000 IU powder and solvent for solution for injection 

One vial contains nominally 1000 IU nonacog gamma, recombinant human coagulation factor IX 

(rDNA), corresponding to a concentration of 200 IU/ml after reconstitution with 5 ml solvent. 

 

RIXUBIS 2000 IU powder and solvent for solution for injection 

One vial contains nominally 2000 IU nonacog gamma, recombinant human coagulation factor IX 

(rDNA), corresponding to a concentration of 400 IU/ml after reconstitution with 5 ml solvent. 

 

RIXUBIS 3000 IU powder and solvent for solution for injection 

One vial contains nominally 3000 IU nonacog gamma, recombinant human coagulation factor IX 

(rDNA), corresponding to a concentration of 600 IU/ml after reconstitution with 5 ml solvent. 

 

The potency (IU) is determined using the European Pharmacopoeia one stage clotting assay. 

The specific activity of RIXUBIS is approximately 200-390 IU/mg protein. 

 

Nonacog gamma (recombinant coagulation factor IX) is a single-chain purified glycoprotein that 

has 415 amino acids. It is produced by recombinant DNA technology in a Chinese hamster ovary 

(CHO) cell line. 

 

Excipient(s) with known effect: 

One vial contains 19 mg sodium. 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder and solvent for solution for injection. 

The powder is white to off-white. The solvent is clear and colourless. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Treatment and prophylaxis of bleeding in patients with haemophilia B (congenital factor IX 

deficiency). 

RIXUBIS is indicated in patients of all age groups. 

 



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4.2 Posology and method of administration 

 

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

 

Treatment monitoring 

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

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

response to factor 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. 

 

To ensure that the desired factor IX activity plasma level has been attained, careful monitoring using 

an appropriate factor IX activity assay is advised and, if necessary, appropriate adjustments to the dose 

and the frequency of repeated infusions should be performed. 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. 

 

Posology 

Dose and duration of the substitution therapy depends on the severity of the factor IX deficiency, on 

the location and extent of the bleeding, and on the patient’s clinical condition, age and 

pharmacokinetic parameters of factor IX, such as incremental recovery and half-life. 

 

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  of factor IX activity is equivalent to that quantity of factor IX in one ml of 

normal human plasma. 

 

Adult population 

On demand treatment: 

The calculation of the required dose of factor IX is based on the empirical finding that 1 International 

Unit  factor IX per kg body weight raises the plasma factor IX activity by 0.9 IU/dL (range 

from 0.5 to 1.4 IU/dL) or 0.9% of normal activity in patients 12 years and older (further information 

see section 5.2). 

 

The required dose is determined using the following formula: 

 

Required 

units 

= body weight (kg) x desired factor IX rise 

(%) or (IU/dL) 

x reciprocal of observed 

recovery (dL/kg) 

 

For an incremental recovery of 0.9 IU/dL per IU/kg, the dose is calculated as follows: 

 

Required 

units 

= body weight (kg) x desired factor IX rise 

(%) or (IU/dL) 

x 1.1 dL/kg 

 

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

clinical effectiveness in the individual case. 

 



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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 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 (%) or 

(IU/dL) 

Frequency of doses 

(hours)/Duration 

of therapy (days) 

 

Haemorrhage 

Early haemarthrosis, muscle 

bleeding or oral bleeding 

 

 

More extensive haemarthrosis, 

muscle bleeding or haematoma 

 

 

Life-threatening haemorrhages. 

 

20 – 40 

 

 

 

 

30 – 60 

 

 

 

60 – 100 

 

Repeat every 24 hours. At least 1 day, 

until the bleeding episode as indicated 

by pain is resolved or healing is 

achieved. 

 

Repeat infusion every 24 hours for  

3 – 4 days or more until pain and 

acute disability are resolved. 

 

Repeat infusion every 8 to 24 hours 

until threat is resolved. 

 

Surgery 

 

Minor surgery including tooth 

extraction 

 

30 – 60 

 

 

 

 

Every 24 hours, at least 1 day, until 

healing is achieved. 

 

Major surgery 

 

 

80 – 100 

(pre- and postoperative) 

 

Repeat infusion every 8 to 24 hours 

until adequate wound healing, then 

therapy for at least another 7 days to 

maintain a factor IX activity of 30% 

to 60% (IU/dl). 

 

Careful monitoring of replacement therapy is especially important in cases of major surgery or 

life-threatening haemorrhages. 

 

Prophylaxis 

For long-term prophylaxis against bleeding in patients with severe haemophilia B, the usual doses 

are 40 to 60 IU of factor IX per kilogram of body weight at intervals of 3 to 4 days for 

patients 12 years and older. In some cases, depending upon the individual patient´s pharmacokinetics, 

age, bleeding phenotype and physical activity, shorter dosage intervals or higher doses may be 

necessary. 

 

Continuous infusion 

Do not administer RIXUBIS by continuous infusion. 

 

Paediatric population 

Patients aged 12 to 17 years of age: 

Posology is the same in adults and paediatric population from 12 to 17. 

 

Patients less than 12 years of age: 

On demand treatment 

The calculation of the required dose of factor IX is based on the empirical finding that 1 International 

Unit factor IX per kg body weight raises the plasma factor IX activity by 0.7 IU/dL (range 

from 0.31 to 1.0 IU/dL) or 0.7% of normal activity in patients less than 12 years of age (further 

information see section 5.2). 

 

The required dosage is determined using the following formula: 

 



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Patients less than 12 years 

 

Required 

units 

= body weight (kg) x desired factor IX rise 

(%) or (IU/dL) 

x reciprocal of observed 

recovery (dL/kg) 

 

For an incremental recovery of 0.7 IU/dL per IU/kg, the dose is calculated as follows: 

 

Required 

units 

= body weight (kg) x desired factor IX rise 

(%) or (IU/dL) 

x 1.4 dL/kg 

 

The same table as for adults can be used to guide dosing in bleeding episodes and surgery (see above). 

 

Prophylaxis 

The recommended dose range for paediatric patients less than 12 years is 40 to 80 IU/kg at intervals 

of 3 to 4 days. In some cases, depending upon the individual patient´s pharmacokinetics, age, bleeding 

phenotype and physical activity, shorter dosage intervals or higher doses may be necessary. 

 

Method of administration 

Intravenous use. 

In case of self-administration or administration by a caregiver appropriate training is needed. 

RIXUBIS should be administered using a rate that ensures the comfort of the patient, up to 

a maximum of 10 ml/min. 

 

After reconstitution, the solution is clear, colourless, free from foreign particles and has a pH 

of 6.8 to 7.2. The osmolality is greater than 240 m osmol/kg. 

 

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

Only plastic luer-lock syringes should be used with this product. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

Known allergic reaction to hamster protein. 

 

4.4 Special warnings and precautions for use 

 

Traceability  

In order to improve 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 have been reported with RIXUBIS. The product contains 

traces of hamster proteins. If symptoms of hypersensitivity occur, patients or their caregivers 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. 

 

The risk is highest during the early phases of initial exposure to factor IX concentrates in previously 

untreated patients (PUPs), in particular in patients with high-risk gene mutations. There have been 

reports in the literature showing an association between the occurrence of a factor IX inhibitor and 

allergic reactions, in particular in patients with a high-risk gene mutation. Therefore, patients 

experiencing allergic reactions should be evaluated for the presence of an inhibitor. 

 

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

 



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Inhibitors 

After repeated treatment with human coagulation factor IX (rDNA) 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 concentrates, 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. 

 

Nephrotic syndrome 

Nephrotic syndrome has been reported following attempted immune tolerance induction in 

haemophilia B patients with factor IX inhibitors. 

 

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 RIXUBIS 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. 

 

Excipient related considerations 

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-

free’. Depending on body weight and Posology of RIXUBIS, patients could receive more than one 

vial. This should be taken into consideration if the patient is on a controlled sodium diet.  

 

Elderly 

Clinical studies of RIXUBIS did not include subjects aged 65 and over. It is not known whether they 

respond differently from younger subjects. As for all patients, dose selection for an elderly patient 

should be individualised. 

 

Paediatric population 

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

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

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

been reported. 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

There are no or limited amount of data from the use of Factor IX in pregnant women. Animal 

reproduction studies have not been conducted with factor IX. 

Factor IX should be used during pregnancy and breast-feeding only if clearly indicated. 



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Breast-feeding 

It is unknown whether Factor IX/metabolites are excreted in human milk. 

 

Fertility 

There is no information on the effects of factor IX on fertility. 

 

4.7 Effects on ability to drive and use machines 

 

RIXUBIS 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 reactions. 

 

Very rarely development of antibodies to hamster protein with related hypersensitivity reactions 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. 

 

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. 

 

Tabulated list of adverse reactions 

Clinical studies with RIXUBIS included 99 subjects with at least one exposure to RIXUBIS reporting 

in total 5 adverse reactions. 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. 

 

Adverse Drug Reactions, from clinical trials and spontaneous reports 

MedDRA Standard System Organ Class Adverse reactions Frequency per Patient 

Immune system disorders Hypersensitivity a) Not known 

Nervous system disorders Dysgeusia Common 

Musculoskeletal and connective tissue 

disorders 

Pain in extremity Common 

 

a) ADR explained in the section below. 

 



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Description of selected adverse reactions 

 

Hypersensitivity 

Allergic type reactions have been manifested by dyspnoea, pruritus, generalised urticaria and rash. 

 

Paediatric population 

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

However, no data are available on previously untreated patients as only previously treated patients 

have been enrolled in the clinical studies; no immunogenicity investigation on inhibitor development 

was therefore made in this at risk population. 

 

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 RIXUBIS have not been characterised. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factor IX. ATC code: B02BD04. 

 

Mechanism of action 

RIXUBIS contains recombinant coagulation factor IX (nonacog gamma). Factor IX is a single chain 

glycoprotein with a molecular mass of about 68,000 Dalton. It is a vitamin K-dependent coagulation 

factor and it is synthesised in the liver. Factor IX is activated by factor XIa in the intrinsic coagulation 

pathway and by factor VII/tissue factor complex in the extrinsic pathway. Activated factor IX, in 

combination with activated factor VIII, activates factor X. Activated factor X converts prothrombin 

into thrombin. Thrombin then converts fibrinogen into fibrin and a clot is formed. 

 

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. 

 

Clinical efficacy and safety 

Prophylaxis and control of bleeding in previously treated patients 12 years and older 

The efficacy of RIXUBIS has been evaluated in the open-label, uncontrolled part of a combined 

phase 1/3 study, in which a total of 73 male, previously treated patients (PTPs) 

between 12 and 59 years of age received RIXUBIS either for prophylaxis and/or for the treatment of 

bleeding episodes on an on-demand basis. All subjects had severe (factor IX level <1%) or moderately 

severe (factor IX level ≤2%) haemophilia B. Fifty-nine PTPs received RIXUBIS for prophylaxis. 

Fifty-six of these PTPs who received RIXUBIS for a minimum of 3 months were included in the 

efficacy evaluation for prophylaxis. An additional 14 PTPs received RIXUBIS for the treatment of 

bleeding episodes only. Subjects in the on-demand cohort had to have at least 12 documented bleeding 

episodes requiring treatment within 12 months prior to enrollment. The mean treatment duration in the 

on-demand cohort was 3.5±1.00 months (median 3.4, ranging from 1.2 to 5.1 months), the mean total 

annualised bleeding rate (ABR) was 33.9±17.37 with a median of 27.0, ranging from 12.9 to 73.1. 

 

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


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The median ABR on prophylaxis with RIXUBIS for all bleeds was 2.0, for spontaneous bleeds 0.0, 

and for joint bleeds 0.0. 24 subjects (42.9%) experienced zero bleeds. 

 

A total of 249 bleeding episodes were treated with RIXUBIS, of which 197 were joint bleeds 

and 52 non-joint bleeds (soft tissue, muscle, body cavity, intracranial and other). Of a total 

of 249 bleeding episodes, 163 were moderate, 71 were minor, and 15 were major. Treatment was 

individualised based on the severity, cause and site of bleed. Of the 249 bleeding episodes, the 

majority (211; 84.7%) were treated with 1-2 infusions. Haemostatic efficacy at resolution of bleed was 

rated excellent or good in 96% of all treated bleeding episodes. 

 

Prophylaxis and control of bleeding in PTPs below 12 years: 

The efficacy of RIXUBIS has been evaluated in a combined phase 2/3 study, in which a total 

of 23 male PTPs between 1.8 and 11.8 years (median age 7.10 years) with 11 patients < 6 years, 

received RIXUBIS for prophylaxis and control of bleeding episodes. All subjects had severe (factor 

IX level <1%) or moderately severe (factor IX level ≤2%) haemophilia B. All 23 subjects received 

prophylactic treatment with RIXUBIS for a minimum of 3 months and were included in the efficacy 

evaluation for prophylaxis. 

 

The median ABR was 2.0, for spontaneous bleeds 0.0 and for joint bleeds 0.0. 

Nine subjects (39.1%) experienced zero bleeds. 

 

A total of 26 bleeding episodes were treated with RIXUBIS, of which 23 bleeds were due to 

injury, 2 spontaneous and 1 of unknown origin. 19 bleeds were non-joint (soft tissue, muscle, body 

cavity, intracranial and other) and 7 were joint bleeds of which 1 was a bleed into a target joint. 

Of the 26 bleeding episodes, 15 were minor, 9 moderate, and 2 major. Treatment was individualised 

based on the severity, cause and site of bleed The majority (23; 88,5%) were treated 

with 1-2 infusions. Haemostatic efficacy at resolution of a bleed was rated excellent or good 

in 96.2% of all treated bleeding episodes. 

 

Perioperative management: 

The safety and efficacy in the perioperative setting was evaluated in a phase 3 prospective, open-label, 

uncontrolled, multicenter study in male PTPs with severe and moderately severe haemophilia B using 

RIXUBIS. The per-protocol efficacy analysis includes 37 surgeries performed in 27 patients 

between 17 and 57 years of age undergoing major or minor surgical, dental or other surgical invasive 

procedures. Twenty procedures were major including 13 orthopaedic and 3 dental 

surgeries. 17 procedures, including 10 dental extractions, were considered minor. Patients undergoing 

major surgeries had to perform a pharmacokinetic (PK) evaluation. All patients were dosed based on 

their most recent individual incremental recovery. The recommended initial loading dose of RIXUBIS 

was to ensure that during surgery, factor IX activity levels of 80-100% for major surgeries 

and 30-60% for minor surgeries were maintained. RIXUBIS was administered by bolus infusions. 

 

Haemostasis was maintained throughout the study duration.  

 

Paediatric population 

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

RIXUBIS 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 

 

Previously treated patients 12 years and older: 

A randomised, blinded, controlled, crossover pharmacokinetic study of RIXUBIS and a comparator 

was conducted in non-bleeding male subjects (≥15 years of age) as part of the combined 

phase 1/3 pivotal study. The subjects received either of the products as a single intravenous infusion. 

The mean (± SD) and median dose of RIXUBIS in the per protocol analysis set (n=25) 

were 74.69±2.37 and 74.25 IU/kg, respectively, with a range of 71.27 to 79.38 IU/kg. The 



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pharmacokinetic parameters were calculated from factor IX activitiy measurements in blood samples 

obtained up to 72 hours following each infusion. 

 

The pharmacokinetic evaluation was repeated for RIXUBIS in an open-label, uncontrolled study with 

RIXUBIS in male subjects who participated in the initial PK crossover study and had received 

prophylaxis with RIXUBIS for 26±1 weeks (mean ± SD) and accumulated at least 30 exposure days 

(EDs) to RIXUBIS. The RIXUBIS dose range in the repeat pharmacokinetics study 

was 64.48 to 79.18 IU/kg (n=23). 

 

Pharmacokinetic parameters for evaluable subjects (per-protocol analysis) are presented in the table 

below. 

 

Parameter RIXUBIS 

Initial cross-over study 

(N=25) 

RIXUBIS 

Repeat Evaluation 

(N=23) 

AUC0-72h (IU.hr/dL)a 

Mean±SD 

Median (range) 

1067.81±238.42 

1108.35 (696.07-1571.16) 

1156.15±259.44 

1170.26 (753.85-1626.81) 

Incremental recovery at Cmax 

(IU/dL:IU/kg)b 

Mean ±SD 

Median (range) 

0.87±0.22 

0.88 (0.53-1.35) 

0.95±0.25 

0.93 (0.52-1.38) 

Half-life (hr) 

Mean±SD 

Median (range) 

26.70±9.55 

24.58 (15.83-52.34) 

25.36±6.86 

24.59 (16.24-42.20) 

Cmax (IU/dL) 

Mean±SD 

Median (range) 

66.22±15.80 

68.10 (41.70-100.30) 

72.75±19.73 

72.40 (38.50-106.30) 

Mean residence time (hr) 

Mean±SD 

Median (range) 

30.82±7.26 

28.93 (22.25-47.78) 

29.88±4.16 

29.04 (21.32-37.52) 

Vssc (dL/kg) 

Mean±SD 

Median (range) 

2.02±0.77 

1.72 (1.10-3.94) 

1.79±0.45 

1.74 (1.12-2.72) 

Clearance (dL/(kg.hr)) 

Mean±SD 

Median (range) 

0.0644±0.0133 

0.0622 (0.0426-0.0912) 

0.0602±0.0146 

0.0576 (0.0413-0.0945) 

a Area under the plasma concentration-time curve from time 0-72 hours post-infusion. 
b Calculated as (Cmax-baseline factor IX) divided by the dose in IU/kg, where Cmax is the maximal 

post-infusion factor IX measurement. 
c Volume of distribution at steady state 

 

Incremental recovery 30 minutes after infusion was determined for all subjects in the combined 

phase 1/3 study at exposure day 1, at their week 5, 13, and 26 visits, and at the time of study 

completion or termination, if it did not coincide with the week 26 visit. The data demonstrate that the 

incremental recovery is consistent over time (see table below). 

 

 Exposure 

Day 1 

(N=73) 

Week 5 

(N=71) 

Week 13 

(N=68) 

Week 26 

(N=55) 

At study 

completion/ 

terminationb 

(N=23) 

Incremental 

recovery 30 min 

after infusion 

(IU/dL: IU/kg)a 

Mean±SD 

Median (range) 

0.79±0.20 

0.78  

(0.26-1.35) 

0.83±0.21 

0.79  

(0.46-1.48) 

0.85±0.25 

0.83  

(0.14-1.47) 

0.89±0.12 

0.88  

(0.52-1.29) 

0.87±0.20 

0.89  

(0.52-1.32) 



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a Calculated as (C30min-baseline factor IX) divided by the dose in IU/kg, where C30min is the factor 

IX measurement 30 minutes after infusion. 
b If not coinciding with week 26 visit. 

 

Paediatric population (previously treated patients younger than 12 years) 

 

All 23 male subjects underwent an initial pharmacokinetic evaluation of RIXUBIS in a non-bleeding 

state as part of the combined phase 2/3 paediatric study. Subjects were randomised to one of two blood 

sampling sequences to reduce the burden of frequent blood draws on the individual subjects. The mean 

(± SD) and median dose of RIXUBIS in the full analysis set (n=23) 

was 75.50 ± 3.016 and 75.25 IU/kg, respectively, with a range of 70.0 to 83.6 IU/kg. The 

pharmacokinetic parameters were calculated from factor IX activity measurements in blood samples 

obtained up to 72 hours following the infusion. 

 

Pharmacokinetic parameters for all subjects (full analysis set) are presented in the table below. 

 

Parameter < 6years 

(N=11) 

6 - < 12 years 

(N=12) 

All 

(N=23) 

AUCinf (IU.hr/dL)a 

Mean±SD 

Median (range) 

723.7 ± 119.00 

717.2 (488-947) 

886.0 ± 133.66 

863.7 (730-1138) 

808.4 ± 149.14 

802.9 (488-1138) 

Half-life (hr) 

Mean±SD 

Median (range) 

27.67 ± 2.66 

27.28 (24.0-32.2) 

23.15 ± 1.58 

22.65 (21.8-27.4) 

25.31 ± 3.13 

24.48 (21.8-32.2) 

Mean residence time (hr) 

Mean±SD 

Median (range) 

30.62 ±3.27 

30.08 (26.2-36.2) 

25.31 ± 1.83 

24.74 (23.7-30.3) 

27.85 ± 3.73 

26.77 (23.7-36.2) 

Vssb (dL/kg) 

Mean±SD 

Median (range) 

3.22 ± 0.52 

3.16 (2.65-4.42) 

2.21 ± 0.32 

2.185 (1.70-2.70) 

2.7 ± 0.67 

2.69 (1.70-4.42) 

Clearance (dL/(kg.hr)) 

Mean±SD 

Median (range) 

0.1058 ± 0.01650 

0.1050 (0.081-0.144) 

0.0874 ± 0.01213 

0.0863 (0.069-0.108) 

0.0962 ± 0.01689 

0.0935 (0.069-0.144) 

a Area under the plasma concentration-time curve from time 0 to infinity. 
b Volume of distribution at steady state 

 

Incremental recovery 30 minutes after infusion was determined for all subjects in the combined 

phase 2/3 study at the initial pharmacokinetic evaluation (exposure day 1), at week 5, 13, and 26 visits, 

and at the time of study completion or termination, if it did not coincide with the week 26 visit. The 

data demonstrate that the incremental recovery is consistent over time across all paediatric age groups. 

See tables below. 

 

Incremental recovery for RIXUBIS 30 minutes after infusion, both paediatric age groups: 

 

Incremental 

recovery 30 min 

after infusion 

PK (ED 1) 

All 

(N=22) 

Week 5 

All 

(N=23) 

Week 13 

All 

(N=21) 

Week 26 

All 

(N=21) 

(IU/dL: IU/kg)a 

Mean±SD 

Median (range) 

0.67 ±0.16 

0.69  

(0.31 – 1.00) 

0.68 ± 0.12 

0.66  

(0.48 – 0.92) 

0.71 ± 0.13 

0.66  

(0.51-1.00) 

0.72 ± 0.15 

0.734  

(0.51-1.01) 
a Calculated as (C30min-baseline factor IX) divided by the dose in IU/kg, where C30min is the factor 

IX measurement 30 minutes after infusion. 

 



12 

Incremental recovery for RIXUBIS 30 minutes after infusion, paediatric patients < 6 years: 

 

Incremental 

recovery 30 min 

after infusion 

PK (ED 1) 

All 

(N=10) 

Week 5 

All 

(N=11) 

Week 13 

All 

(N=10) 

Week 26 

All 

(N=10) 

(IU/dL: IU/kg)a 

Mean±SD 

Median (range) 

0.59 ± 0.13 

0.59  

(0.31-0.75) 

0.63 ± 0.10 

0.6  

(0.49-0.80) 

0.68 ± 0.12 

0.66  

(0.51-0.84) 

0.65 ± 0.13 

0.61  

(0.51-0.84) 
a Calculated as (C30min-baseline factor IX) divided by the dose in IU/kg, where C30min is the factor 

IX measurement 30 minutes after infusion. 

 

Incremental recovery for RIXUBIS 30 minutes after infusion, paediatric patients 6 to < 12 years: 

 

Incremental 

recovery 30 min 

after infusion 

PK (ED 1) 

All 

(N=12) 

Week 5 

All 

(N=12) 

Week 13 

All 

(N=11) 

Week 26 

All 

(N=11) 

(IU/dL: IU/kg)a 

Mean±SD 

Median (range) 

0.73 ± 0.16 

0.71 (0.51-1.00) 

0.73 ± 0.13 

0.70 (0.48-0.92) 

0.73 ± 0.14 

0.70 (0.54 – 1.00) 

0.8 ± 0.14 

0.78 (0.56-1.01) 

a Calculated as (C30min-baseline factor IX) divided by the dose in IU/kg, where C30min is the factor 

IX measurement 30 minutes after infusion. 

 

5.3 Preclinical safety data 

 

RIXUBIS was not thrombogenic at a dose of 750 IU/kg in a rabbit stasis model (Wessler-Test). 

RIXUBIS did not cause any adverse clinical, respiratory, or cardiovascular effects up to 450 IU/kg in 

cynomolgus monkeys. 

No investigations on carcinogenicity, fertility impairment, and fetal development have been 

conducted. 

RIXUBIS was well tolerated in single dose and repeated dose toxicity studies conducted in mice, rats 

and cynomolgus monkeys up to doses of 7500 IU/kg (single dose) and 750 IU/kg (repeated 

application). 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Powder 

Sucrose 

Mannitol 

Sodium chloride 

Calcium chloride 

L-Histidine 

Polysorbate 80 

 

Solvent 

Sterilised water for injections 

 

6.2 Incompatibilities 

 

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

products. 

 

Only plastic luer-lock syringes should be used with this product. Incorrect dosing can occur as a 

consequence of human coagulation factor IX adsorption to the internal surfaces of some infusion 

equipment. 



13 

6.3 Shelf life 

 

3 years. 

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

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

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

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

 

6.4 Special precautions for storage 

 

Store below 30°C. 

Do not freeze. 

 

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 

 

One pack contains a powder vial (type I glass) with a stopper (butyl rubber) and a flip-off seal, a vial 

containing 5 ml solvent (type I glass) with a stopper (chlorobutyl rubber) and a flip-off seal and a 

needle-less reconstitution device (BAXJECT II). 

Pack size of 1. 

 

6.6 Special precautions for disposal and other handling 

 

RIXUBIS is to be administered intravenously after reconstitution of the powder with the provided 

solvent. 

 

- For reconstitution use only the solvent and the reconstitution device (BAXJECT II) provided in 
the pack. 

- For administration the use of a luer-lock syringe is required. 
- Do not use if the BAXJECT II device, its sterile barrier system or its packaging is damaged or 

shows any sign of deterioration. 

 

Reconstitution 

Use Aseptic Technique 

 

1. If the product is  stored in a refrigerator, take both the RIXUBIS powder and solvent vials from 

the refrigerator and let them reach room temperature (between 15°C and 30°C). 

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

3. Remove caps from powder and solvent vials. 

4. Cleanse stoppers with alcohol swabs. Place the vials on a flat clean surface. 

5. Open the package of BAXJECT II device by peeling away the paper lid without touching the 

inside (Fig. a). Do not remove the device from the package. 

6. Turn the package over and insert the clear plastic spike through the solvent stopper. Grip the 

package at its edge and pull the package off BAXJECT II (Fig. b). Do not remove the blue cap 

from the BAXJECT II device. 

7. With BAXJECT II attached to the solvent vial, invert the system so that the solvent vial is on 

top of the device. Insert the white plastic spike through the RIXUBIS stopper. The vacuum will 

draw the solvent into the RIXUBIS vial (Fig. c). 



14 

8. Swirl gently until all material is dissolved. The product dissolves rapidly (within 2 minutes). 

Be sure that RIXUBIS is completely dissolved, otherwise not all reconstituted solution will pass 

through the device filter. Reconstituted medicinal products should be inspected visually for 

particulate matter and discoloration prior to administration. The solution should be clear or 

slightly opalescent. Do not use solutions that are cloudy or have deposits. 

 

Fig. a  Fig. b Fig. c 

    
 

Do not refrigerate the preparation after reconstitution. 

Use immediately. 

 

Administration 

Use Aseptic Technique 

 

1. Remove the blue cap from BAXJECT II. Do not draw air into the syringe. Connect the 

syringe to BAXJECT II (Fig. d). 

2. Invert the system (the vial with the reconstituted solution has to be on top). Draw the 

reconstituted solution into the syringe by pulling the plunger back slowly (Fig. e). 

3. Disconnect the syringe. 

4. Attach a butterfly needle to the syringe. Inject intravenously. The solution should be 

administered slowly, at a rate as determined by the patient’s comfort level, not to exceed 10 ml 

per minute. 

 

Fig. d Fig. e 

  
 

Whenever possible, please record the name of the product and the batch number every time you use 

RIXUBIS (e.g. in your diary) to keep track of the products and product batches you have used. 

 

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

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

Industriestrasse 67 

A-1221 Vienna 

Austria 



15 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/14/970/001 

EU/1/14/970/002 

EU/1/14/970/003 

EU/1/14/970/004 

EU/1/14/970/005 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 19 December 2014 

Date of latest renewal: DD month YYYY 

 

 

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/


16 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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 

 

 



17 

A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 

MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer of the biological active substance 

 

Baxter AG 

Uferstraße 15 

A-2304 Orth an der Donau 

Austria 

 

Name and address of the manufacturers responsible for batch release 

 

Baxalta Belgium Manufacturing SA 

Boulevard René Branquart 80 

B-7860 Lessines 

Belgium 

 

Baxter SA 

Boulevard René Branquart 80 

B-7860 Lessines 

Belgium 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

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

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic safety update reports (PSURs) 
 

The requirements for submission of 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 and published on the European medicines 

web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk management plan (RMP) 
 

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

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

subsequent updates of the RMP. 

 



18 

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 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

RIXUBIS 250 IU powder and solvent for solution for injection 

nonacog gamma (recombinant human coagulation factor IX) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 250 IU nonacog gamma, approx. 50 IU/ml after reconstitution with 5 ml solvent. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: sodium chloride, sucrose, calcium chloride, histidine, mannitol, polysorbate 80. 

 

Solvent: sterilised water for injections 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

Contents: 1 powder vial, 1 solvent vial, 1 BAXJECT II device 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

For intravenous use, single use only. 

 

 

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 immediately. 

 

 



22 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 30°C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/14/970/001 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

RIXUBIS 250 

 

 

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 

 

VIAL LABEL FOR THE POWDER 

 

 

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

 

RIXUBIS 250 IU powder for injection 

nonacog gamma 

IV use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use injection. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

250 IU 

 

 

6. OTHER 

 



24 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE SOLVENT 

 

 

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

 

Sterilised water for injections 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

5 ml 

 

 

6. OTHER 

 



25 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

RIXUBIS 500 IU powder and solvent for solution for injection 

nonacog gamma (recombinant human coagulation factor IX) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 500 IU nonacog gamma, approx. 100 IU/ml after reconstitution with 5 ml solvent. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: sodium chloride, sucrose, calcium chloride, histidine, mannitol, polysorbate 80. 

 

Solvent: sterilised water for injections 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

Contents: 1 powder vial, 1 solvent vial, 1 BAXJECT II device 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

For intravenous use, single use only. 

 

 

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 immediately. 

 

 



26 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 30°C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/14/970/002 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

RIXUBIS 500 

 

 

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 

 

VIAL LABEL FOR THE POWDER 

 

 

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

 

RIXUBIS 500 IU powder for injection 

nonacog gamma 

IV use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use injection. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

500 IU 

 

 

6. OTHER 

 



28 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE SOLVENT 

 

 

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

 

Sterilised water for injections 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

5 ml 

 

 

6. OTHER 

 



29 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

RIXUBIS 1000 IU powder and solvent for solution for injection 

nonacog gamma (recombinant human coagulation factor IX) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 1000 IU nonacog gamma, approx. 200 IU/ml after reconstitution with 5 ml solvent. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: sodium chloride, sucrose, calcium chloride, histidine, mannitol, polysorbate 80. 

 

Solvent: sterilised water for injections 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

Contents: 1 powder vial, 1 solvent vial, 1 BAXJECT II device 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

For intravenous use, single use only. 

 

 

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 immediately. 

 

 



30 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 30°C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/14/970/003 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

RIXUBIS 1000 

 

 

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 

 

VIAL LABEL FOR THE POWDER 

 

 

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

 

RIXUBIS 1000 IU powder for injection 

nonacog gamma 

IV use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use injection. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1000 IU 

 

 

6. OTHER 

 



32 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE SOLVENT 

 

 

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

 

Sterilised water for injections 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

5 ml 

 

 

6. OTHER 

 



33 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

RIXUBIS 2000 IU powder and solvent for solution for injection 

nonacog gamma (recombinant human coagulation factor IX) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 2000 IU nonacog gamma, approx. 400 IU/ml after reconstitution with 5 ml solvent. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: sodium chloride, sucrose, calcium chloride, histidine, mannitol, polysorbate 80. 

 

Solvent: sterilised water for injections 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

Contents: 1 powder vial, 1 solvent vial, 1 BAXJECT II device 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

For intravenous use, single use only. 

 

 

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 immediately. 

 

 



34 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 30°C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/14/970/004 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

RIXUBIS 2000 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



35 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER 

 

 

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

 

RIXUBIS 2000 IU powder for injection 

nonacog gamma 

IV use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use injection. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

2000 IU 

 

 

6. OTHER 

 



36 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE SOLVENT 

 

 

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

 

Sterilised water for injections 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

5 ml 

 

 

6. OTHER 

 



37 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

OUTER CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

RIXUBIS 3000 IU powder and solvent for solution for injection 

nonacog gamma (recombinant human coagulation factor IX) 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

1 vial: 3000 IU nonacog gamma, approx. 600 IU/ml after reconstitution with 5 ml solvent. 

 

 

3. LIST OF EXCIPIENTS 

 

Excipients: sodium chloride, sucrose, calcium chloride, histidine, mannitol, polysorbate 80. 

 

Solvent: sterilised water for injections 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder and solvent for solution for injection 

 

Contents: 1 powder vial, 1 solvent vial, 1 BAXJECT II device 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

For intravenous use, single use only. 

 

 

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 immediately. 

 

 



38 

9. SPECIAL STORAGE CONDITIONS 

 

Store below 30°C. 

Do not freeze. 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Baxalta Innovations GmbH 

A-1221 Vienna 

Austria 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/14/970/005 

 

 

13. BATCH NUMBER 

 

Lot: 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

RIXUBIS 3000 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC: 

SN: 

NN: 

 

 



39 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE POWDER 

 

 

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

 

RIXUBIS 3000 IU powder for injection 

nonacog gamma 

IV use 

 

 

2. METHOD OF ADMINISTRATION 

 

Read the package leaflet before use. 

Single use injection. 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

3000 IU 

 

 

6. OTHER 

 



40 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL FOR THE SOLVENT 

 

 

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

 

Sterilised water for injections 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP: 

 

 

4. BATCH NUMBER 

 

Lot: 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

5 ml 

 

 

6. OTHER 

 

  



41 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



42 

Package leaflet: Information for the user 

 

RIXUBIS 250 IU powder and solvent for solution for injection 

RIXUBIS 500 IU powder and solvent for solution for injection 

RIXUBIS 1000 IU powder and solvent for solution for injection 

RIXUBIS 2000 IU powder and solvent for solution for injection 

RIXUBIS 3000 IU powder and solvent for solution for injection 

 

nonacog gamma (recombinant human coagulation factor IX) 

 

 

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

important information for you. 

 

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

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

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

 

What is in this leaflet 

 

1. What RIXUBIS is and what it is used for 

2. What you need to know before you use RIXUBIS 

3. How to use RIXUBIS 

4. Possible side effects 

5. How to store RIXUBIS 

6. Contents of the pack and other information 

 

 

1. What RIXUBIS is and what it is used for 

 

RIXUBIS contains the active substance nonacog gamma and is a coagulation factor IX product. Factor 

IX is a normal constituent of human blood necessary for effective blood clotting. RIXUBIS is used in 

patients with haemophilia B (Christmas disease, an inherited bleeding disorder caused by lack of 

factor IX). It works by replacing the missing factor IX to enable the patient’s blood to clot. 

 

RIXUBIS is used for the treatment and prevention of bleeding in patients with haemophilia B of all 

age groups. 

 

 

2. What you need to know before you use RIXUBIS 

 

Do not use RIXUBIS 

- if you are allergic to nonacog gamma or any of the other ingredients of this medicine (listed in 
section 6) 

- if you are allergic to hamster proteins 
 

Warnings and precautions 

Allergic-type hypersensitivity reactions are possible with RIXUBIS. Stop your infusion and contact 

your doctor immediately or seek emergency medical care if you experience early signs of 

hypersensitivity/allergic reactions like hives, rash, tightness of the chest, wheezing, low blood pressure 

or anaphylaxis (severe allergic reaction that can cause difficulty in swallowing and/or breathing, red or 

swollen face and/or hands). Your doctor may need to treat you promptly for these reactions. Your 

doctor may also do a blood test to check if you have developed activity-neutralising antibodies 



43 

(inhibitors) against your medicine, as inhibitors may develop together with allergies. Patients with 

factor IX inhibitors may be at an increased risk of anaphylaxis during future treatment with factor IX. 

 

Talk to your doctor immediately if your bleeding does not stop as expected or if you experience a 

significant increase in your usage of RIXUBIS in order to control a bleed. Your doctor will do a blood 

test to check if you have developed activity-neutralising antibodies (inhibitors) against RIXUBIS. The 

risk for developing inhibitors is highest in patients who have not been treated with a factor IX 

replacement medicine before or in the early phases of treatment, i.e. for small children. 

 

The production of factor IX in the body is controlled by the factor IX gene. Patients who have specific 

mutations of their factor IX gene such as major deletion may be more likely to have factor IX 

inhibitors and an allergic reaction in the early period with any factor IX concentrate. Therefore if you 

are known to have such a mutation, your doctor will monitor you more closely for signs of an allergic 

reaction. 

 

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. 

 

Kidney disorders (nephrotic syndrome) have been reported following high doses of Factor IX in 

haemophilia B patients with factor IX inhibitors and a history of allergic reactions. 

 

Whenever possible, please record the name of the product and the batch number every time you use 

RIXUBIS (e.g. in your diary) to keep track of the products and product batches you have used. 

 

Other medicines and RIXUBIS 

Tell your doctor if you are using or have recently used or might use any other medicines. No 

interactions of RIXUBIS with other medicines are known. 

 

Pregnancy, breast-feeding and fertility 

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

your doctor for advice before using this medicine. Haemophilia B very rarely occurs in women. 

 

Driving and using machines 

RIXUBIS has no influence on the ability to drive and use machines. 

 

RIXUBIS contains sodium 

This medicine contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially ‘sodium-

free’. However, depending on your body weight and your dose of RIXUBIS, you could receive more 

than one vial. This should be taken into consideration if you are on a controlled sodium diet.  

 

 

3. How to use RIXUBIS 

 

Treatment with RIXUBIS will be started by a doctor who is experienced in the care of patients with 

haemophilia B. 

 

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

sure. 

 

Your doctor will decide the dose of RIXUBIS you will receive. This dose and duration will depend on 

the severity of your factor IX deficiency, on the location and extent of the bleeding and on your 

clinical condition, age and how quickly your body uses up factor IX which will have to be checked 

regularly. 

 

RIXUBIS is administered by intravenous infusion (IV) after reconstitution of the powder with the 

provided solvent by your doctor or nurse. You or somebody else might also administer RIXUBIS as 

an injection but only after receiving adequate training. 



44 

Reconstitution and administration 

 

- For reconstitution use only the solvent and the reconstitution device (BAXJECT II) provided in 
the pack. 

- For administration the use of a luer-lock syringe is required. 
- Do not use if the BAXJECT II device, its sterile barrier system or its packaging is damaged or 

shows any sign of deterioration. 

 

Reconstitution 

Use Aseptic Technique 

 

1. If the product is stored in a refrigerator, take both the RIXUBIS powder and solvent vials from 

the refrigerator and let them reach room temperature (between 15°C and 30°C). 

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

3. Remove caps from powder and solvent vials. 

4. Cleanse stoppers with alcohol swabs. Place the vials on a flat clean surface. 

5. Open the package of BAXJECT II device by peeling away the paper lid without touching the 

inside (Fig. a). Do not remove the device from the package. 

6. Turn the package over and insert the clear plastic spike through the solvent stopper. Grip the 

package at its edge and pull the package off BAXJECT II (Fig. b). Do not remove the blue cap 

from the BAXJECT II device. 

7. With BAXJECT II attached to the solvent vial, invert the system so that the solvent vial is on 

top of the device. Insert the white plastic spike through the RIXUBIS stopper. The vacuum will 

draw the solvent into the RIXUBIS vial (Fig. c). 

8. Swirl gently until all material is dissolved. The product dissolves rapidly (within 2 minutes). 

Be sure that RIXUBIS is completely dissolved, otherwise not all reconstituted solution will pass 

through the device filter. Reconstituted medicinal products should be inspected visually for 

particulate matter and discoloration prior to administration. The solution should be clear or 

slightly opalescent. Do not use solution that are cloudy or have deposits. 

 

Fig. a  Fig. b Fig. c 

    
 

Do not refrigerate the preparation after reconstitution. 

Use immediately. 

 

Administration 

Use Aseptic Technique 

 

1. Remove the blue cap from BAXJECT II. Do not draw air into the syringe. Connect the 

syringe to BAXJECT II (Fig. d). 

2. Invert the system (the vial with the reconstituted solution has to be on top). Draw the 

reconstituted solution into the syringe by pulling the plunger back slowly (Fig. e). 

3. Disconnect the syringe. 



45 

4. Attach a butterfly needle to the syringe. Inject intravenously. The solution should be 

administered slowly, at a rate as determined by the patient’s comfort level, not to exceed 10 ml 

per minute. 

 

Fig. d Fig. e 

  
Whenever possible, please record the name of the product and the batch number every time you use 

RIXUBIS (e.g. in your diary) to keep track of the products and product batches you have used. 

 

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

 

If you use more RIXUBIS than you should 

Always use RIXUBIS exactly as your doctor has told you. If you are not sure check with your doctor. 

If you injected more RIXUBIS than recommended, tell your doctor as soon as possible. 

 

If you forget to use RIXUBIS 

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

scheduled and continue as advised by your doctor. 

 

If you stop using RIXUBIS 

Do not stop using RIXUBIS without consulting your doctor. 

 

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

 

 

4. Possible side effects 

 

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

 

Allergic-type hypersensitivity reactions are possible with RIXUBIS. Such reactions may include 

burning sensations and stinging at the infusion site, chills, flushing, lethargy, restlessness, tingling, 

hives, itching and rash, low blood pressure, fast heart rate, tightness of the chest, wheezing, swelling 

of the throat, anaphylaxis (severe allergic reaction), headache, nausea and vomiting. Please, contact 

your doctor immediately if you experience such signs. Your doctor may need to treat you promptly for 

these reactions (see section 2 ‘Warnings and precautions’). 

 

The following side effects have been observed with RIXUBIS: 

 

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

- altered taste 
- pain in limbs. 
 

Side effects with unknown frequency (frequency cannot be estimated from the available data) 

- allergic reactions (hypersensitivity). 
 

Problems from exaggerated blood clotting (thromboembolic episodes) have not been observed with 

this product, but may occur with any factor IX products. These may include heart attack, blood clots in 

the veins or blood clots in the lung. 



46 

Reporting of side effects 

If you get any side effects, talk to your doctor or, pharmacist. 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 RIXUBIS 

 

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

 

Do not use this medicine after the expiry date which is stated on the outer box and vial label after 

EXP. The expiry date refers to the last day of that month. 

 

Store below 30°C. 

Do not freeze. 

 

Use the reconstituted solution immediately. 

 

Do not use RIXUBIS if the solution is not clear and colourless. 

 

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

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

 

 

6. Contents of the pack and other information 

 

What RIXUBIS contains 

- The active substance is nonacog gamma (recombinant human coagulation Factor IX). Each 
powder vials contains nominally 250, 500, 1000, 2000 or 3000 IU, corresponding to a 

concentration of 50, 100, 200, 400 or 600 IU/ml after reconstitution with 5 ml solvent. 

- The other ingredients in the powder are sucrose, mannitol, sodium chloride, calcium chloride, 
L-histidine, polysorbate 80. 

 

Solvent vial: 5 ml sterilised water for injections. 

 

What RIXUBIS looks like and contents of the pack 

 

RIXUBIS is provided as a powder and solvent for solution for injection. 

 

The contents of the pack are: 

 

• one vial of RIXUBIS 250, 500, 1000, 2000 or 3000 IU powder in a glass vial with a rubber 
stopper 

• one vial of 5 ml sterilised water for injections in a glass vial with a rubber stopper 

• one BAXJECT II (needle-less reconstitution device) 
 

Marketing Authorisation Holder 

 

Baxalta Innovations GmbH 

Industriestrasse 67 

A-1221 Vienna 

Austria 

Tel.: +800 66838470 

E-mail: medinfoEMEA@shire.com 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc
mailto:medinfoEMEA@shire.com


47 

Manufacturer 

 

Baxalta Belgium Manufacturing SA 

Boulevard René Branquart 80 

B-7860 Lessines 

Belgium 

 

Baxter SA 

Boulevard René Branquart 80 

B-7860 Lessines 

Belgium 

 

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: 

 

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 

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. 

 

To ensure that the desired factor IX activity plasma level has been attained, careful monitoring using 

an appropriate factor IX activity assay is advised and, if necessary, appropriate adjustments to the dose 

and the frequency of repeated infusions should be performed. 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. 

 

Posology 

Dose and duration of the substitution therapy depends on the severity of the factor IX deficiency, on 

the location and extent of the bleeding, and on the patient’s clinical condition, age and 

pharmacokinetic parameters of factor IX, such as incremental recovery and half-life. 

 

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  of factor IX activity is equivalent to that quantity of factor IX in one ml of 

normal human plasma. 

 

Adult population 

On demand treatment: 

The calculation of the required dose of factor IX is based on the empirical finding that 1 International 

Unit factor IX per kg body weight raises the plasma factor IX activity by 0.9 IU/dL (range 

from 0.5 to 1.4 IU/dL) or 0.9% of normal activity in patients 12 years and older (further information 

see section 5.2). 

 

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


48 

The required dose is determined using the following formula: 

 

Required 

units 

= body weight (kg) x desired factor IX rise 

(%) or (IU/dL) 

x reciprocal of observed 

recovery (dL/kg) 

 

For an incremental recovery of 0.9 IU/dL per IU/kg, the dose is calculated as follows: 

 

Required 

units 

= body weight (kg) x desired factor IX rise 

(%) or (IU/dL) 

x 1.1 dL/kg 

 

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

clinical effectiveness in the individual case. 

 

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

plasma activity level (in % of normal or IU/dL) in the corresponding period. The following table can 

be used to guide dosing in bleeding episodes and surgery: 

 

Degree of haemorrhage/Type 

of surgical procedure 

Factor IX level 

required (%) or 

(IU/dL) 

Frequency of doses 

(hours)/Duration 

of therapy (days) 

 

Haemorrhage 

Early haemarthrosis, muscle 

bleeding or oral bleeding 

 

 

More extensive haemarthrosis, 

muscle bleeding or haematoma 

 

 

Life-threatening haemorrhages. 

 

20 – 40 

 

 

 

 

30 – 60 

 

 

 

60 – 100 

 

Repeat every 24 hours. At least 1 day, 

until the bleeding episode as indicated 

by pain is resolved or healing is 

achieved. 

 

Repeat infusion every 24 hours for  

3 – 4 days or more until pain and 

acute disability are resolved. 

 

Repeat infusion every 8 to 24 hours 

until threat is resolved. 

 

Surgery 

 

Minor surgery including tooth 

extraction 

 

30 – 60 

 

 

 

 

Every 24 hours, at least 1 day, until 

healing is achieved. 

 

Major surgery 

 

 

80 – 100 

(pre- and postoperative) 

 

Repeat infusion every 8 to 24 hours 

until adequate wound healing, then 

therapy for at least another 7 days to 

maintain a factor IX activity of 30% 

to 60% (IU/dl). 

 

Careful monitoring of replacement therapy is especially important in cases of major surgery or 

life-threatening haemorrhages. 

 

Prophylaxis 

For long-term prophylaxis against bleeding in patients with severe haemophilia B, the usual doses 

are 40 to 60 IU of factor IX per kilogram of body weight at intervals of 3 to 4 days for 

patients 12 years and older. In some cases, depending upon the individual patient´s pharmacokinetics, 

age, bleeding phenotype and physical activity, shorter dosage intervals or higher doses may be 

necessary. 

 

Continuous infusion 

Do not administer RIXUBIS by continuous infusion. 

 



49 

Paediatric population 

Patients aged 12 to 17 years of age: 

Posology is the same in adults and paediatric population from 12 to 17. 

 

Patients less than 12 years: 

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 raises the plasma factor IX activity by 0.7 IU/dL (range 

from 0.31 to 1.0 IU/dL) or 0.7% of normal activity in patients less than 12 years of age (further 

information see section 5.2). 

 

The required dosage is determined using the following formula: 

 

Patients less than 12 years: 

 

Required 

units 

= body weight (kg) x desired factor IX rise 

(%) or (IU/dL) 

x reciprocal of observed 

recovery (dL/kg) 

 

For an incremental recovery of 0.7 IU/dL per IU/kg, the dose is calculated as follows: 

 

Required 

units 

= body weight (kg) x desired factor IX rise 

(%) or (IU/dL) 

x 1.4 dL/kg 

 

The same table as for adults can be used to guide dosing in bleeding episodes and surgery (see above). 

 

Prophylaxis: 

The recommended dose range for paediatric patients less than 12 years is 40 to 80 IU/kg at intervals 

of 3 to 4 days. In some cases, depending upon the individual patient´s pharmacokinetics, age, bleeding 

phenotype and physical activity, shorter dosage intervals or higher doses may be necessary. 

 

 


	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