Obizur

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
OBIZUR 500 U powder and solvent for solution for injection 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each powder vial contains nominally 500 Units of B domain deleted antihaemophilic Factor VIII 
(recombinant), porcine sequence, susoctocog alfa. 
 
OBIZUR contains approximately 500 U/ml susoctocog alfa after reconstitution. 
 
The potency (U) is determined using the one-stage coagulation assay (OSCA). The specific activity of 
OBIZUR is approximately 10,000 U/mg protein. 
 
OBIZUR (antihaemophilic Factor VIII (recombinant), porcine sequence) is a purified protein that 
has 1448 amino acids with an approximate molecular mass of 175kDa. 
It is produced by recombinant DNA (rDNA) technology in baby hamster kidney (BHK) cells. The 
BHK cells are cultured in media that contains fetal bovine serum. The manufacturing process is free of 
human serum and human protein products and does not contain any additional animal derived 
materials. 
 
Excipient(s) with known effect 
Each vial contains 4.4 mg (198 mM) sodium per ml of reconstituted solution. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Powder and solvent for solution for injection. 
The powder is white. 
The solvent is clear and colourless. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of bleeding episodes in patients with acquired haemophilia caused by antibodies to Factor 
VIII. 
 
OBIZUR is indicated in adults. 
 
4.2 Posology and method of administration 
 
Treatment with OBIZUR should be under the supervision of a physician experienced in the treatment 
of haemophilia. 
 
The product is for in-patient administration only. It requires clinical supervision of the bleeding status 
of the patient. 
 



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Posology 
 
The dose, frequency, and duration of the therapy with OBIZUR depend on the location, extent and 
severity of the bleeding episode, target Factor VIII activity, and on the patient´s clinical condition. 
 
The number of units of Factor VIII administered is expressed in Units (U) that are derived from an 
in-house standard that has been calibrated with the current WHO standard for Factor VIII products. 
One Unit (U) of Factor VIII activity is equivalent to that quantity of Factor VIII in one ml of normal 
human plasma. 
 
The recommended initial dose is 200 U per kilogram bodyweight, given by intravenous injection (see 
section 6.6). 
 
The required initial dose of OBIZUR for a patient is calculated using the following formula: 
 

Initial dose (U/kg) ÷ Product strength (U/vial) × Body weight (kg) = Number of vials 
 
e.g. for a 70 kg subject the number of vials for an initial dose will be calculated as follows: 

200 U/kg ÷ 500 U/vial × 70 kg = 28 vials 
 
Monitor Factor VIII activity and clinical condition 30 minutes after the first injection and 3 hours after 
administering OBIZUR. 
Monitor Factor VIII activity immediately prior to and 30 minutes after subsequent doses and refer to 
the table below for recommended target Factor VIII trough levels. 
The one-stage clotting assay for Factor VIII is recommended as it has been used in determination of 
the potency of OBIZUR and the mean recovery rate (see section 4.4 and 5.2). 
 
The dose and frequency of administration should be based on results of Factor VIII activity (to be 
maintained within recommended limits) and on the clinical response achieved. 
 
Efficacy and safety data in patients with acquired haemophilia are limited (see section 5.1). 
 
Initial Phase 
 
Type of Bleeding  Target Factor VIII 

Trough Activity 
(Units per dL or % of 
normal) 

Initial 
Dose 
(Units per 
kg) 
 

Subsequent 
Dose 

Frequency and 
Duration of 
Subsequent 
Dosing  

Mild and moderate 
superficial muscle / 
no neurovascular 
compromise and 
joint bleeding 

> 50% 

200 

Titrate 
subsequent 
doses based on 
clinical response 
and to maintain 
target Factor 
VIII trough 
activity 
 

Dose 
every 4 to 12 hours, 
frequency may be 
adjusted based on 
clinical response 
and measured 
Factor VIII activity 
 

Major moderate to 
severe 
intramuscular, 
retroperitoneal, 
gastrointestinal, 
intracranial bleeding 
 

> 80% 

 



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Healing phase 
 
Once bleeding has responded, usually within the first 24 hours, continue OBIZUR with a dose that 
maintains the trough FVIII activity at 30-40% until bleeding is controlled. The maximum blood FVIII 
activity must not exceed 200%. 
 
The length of treatment depends on clinical judgement. 
 
Paediatric population 
 
Use in children and adolescents below 18 years with congenital or in rare cases of acquired 
haemophilia is currently not approved. 
 
Method of administration 
 
Intravenous use. 
 
The total volume of reconstituted OBIZUR should be administered at a rate of 1 to 2 mL per minute. 
 
For instructions on reconstitution of the medicinal product before administration, see section 6.6. 
 
4.3 Contraindications 
 
Known anaphylactic reactions to the active substance, hamster protein, or to any of the excipients 
listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Hypersensitivity 
 
Allergic type hypersensitivity reactions are possible with OBIZUR. The product contains trace 
amounts of hamster proteins. 
If symptoms of hypersensitivity occur, patients should be advised to discontinue use of the medicinal 
product immediately and contact their physician. Patients should be informed of the early signs of 
hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, wheezing, 
hypotension, and anaphylaxis. 
 
In case of shock, standard medical treatment for shock should be implemented. 
 
Development of inhibitory antibodies 
 
Inhibitory antibodies against porcine Factor VIII (measured using a modification of the Nijmegen 
variation of the Bethesda assay) were detected before and after exposure to OBIZUR. Inhibitor titres 
of up to 29 Bethesda units were recorded at baseline yet subjects responded positively to OBIZUR. It 
is recommended that treatment should be based on clinical judgement and not based on detection of 
inhibitory antibodies by the Bethesda assay. 
 
There is a lack of clinical information on the development of inhibitory antibodies to OBIZUR 
following repeated administration. Therefore, OBIZUR must only be administered when considered 
clinically necessary. Extensive cutaneous purpura do not necessarily require treatment. 
 
OBIZUR is produced by recombinant DNA technology in baby hamster kidney cells. Antibodies to 
baby hamster kidney cell protein were not detected in subjects after exposure to OBIZUR. 
 
High and sustained Factor VIII activity in blood may predispose to thromboembolic events. Those 
with pre-existing cardiovascular disease and the elderly are at particular risk. 
 



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If venous catheterisation is required, the risk of catheter-related complications such as catheter site 
thrombosis should be considered. 
 
Factor VIII activity determined by the chromogenic assay is generally lower than Factor VIII activity 
determined by the one-stage clotting assay. Measurement of Factor VIII activity must always be 
carried out using the same assay methodology on any one patient. The one-stage assay is 
recommended because it has been used in determination of the potency and the mean recovery rate of 
OBIZUR (see sections 4.2 and 5.2). 
 
Name and batch number 
It is strongly recommended that every time that OBIZUR 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. 
 
Sodium content 
Each vial contains 4.4 mg (198 mM) sodium per ml of reconstituted solution. 
To be taken into consideration by patients on a controlled sodium diet. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interactions of OBIZUR with other medicinal products have been reported. 
 
4.6 Fertility, pregnancy and lactation 
 
Animal reproduction studies have not been conducted with OBIZUR. Experience regarding the use of 
OBIZUR during pregnancy and breast-feeding is not available. Therefore, OBIZUR should be used 
during pregnancy and lactation only if clearly indicated. 
 
4.7 Effects on ability to drive and use machines 
 
OBIZUR has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile: 
 
Hypersensitivity or allergic reactions (which may include angioedema, burning and stinging at the 
injection site, chills, flushing, generalized urticaria, headache, hives, hypotension, lethargy, nausea, 
restlessness, tachycardia, tightness of the chest, tingling, vomiting, wheezing) are possible and may 
progress to severe anaphylaxis (including shock) (see section 4.4). 
 
Patients with acquired haemophilia may develop inhibitory antibodies to porcine Factor VIII. 
 
Tabulated list of adverse reactions: 
 
The table presented below is according to the MedDRA system organ classification (SOC and 
Preferred Term Level). In the clinical trial of OBIZUR for acquired haemophilia, 29 adult subjects 
were evaluable for safety. 
 
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).  
 
System Organ Class Preferred MedDRA term Frequency  
Investigations Positive test for inhibitory 

antibodies against porcine Factor 
VIII (see section 4.4) 

Common 



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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 the national reporting system listed 
in Appendix V. 
 
4.9 Overdose 
 
The effects of higher than recommended doses of OBIZUR have not been characterised. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: antihaemorrhagics, blood coagulation Factor VIII, porcine sequence. 

ATC code: B02BD14 
 
Mechanism of action 
Obizur is a recombinant, B-domain deleted, porcine sequence Factor VIII (susoctocog alfa). It is a 
glycoprotein. 
Immediately after release in the patient’s circulation, Factor VIII binds to von Willebrand factor 
(vWF). The Factor VIII/von Willebrand factor complex consists of two molecules (Factor VIII and 
von Willebrand factor) with different physiological functions. Activated Factor VIII acts as a co-factor 
for activated Factor IX, accelerating the conversion of Factor X to activated Factor X, which 
ultimately converts prothrombin into thrombin. Thrombin then converts fibrinogen into fibrin and a 
clot can be formed. 
 
Acquired haemophilia is a rare bleeding disorder in which patients with normal Factor VIII genes 
develop inhibitory autoantibodies directed against Factor VIII. These autoantibodies neutralize 
circulating human Factor VIII thus creating a deficiency of available Factor VIII. Circulating 
antibodies (inhibitors) targeted against human Factor VIII have minimal or no cross reactivity against 
OBIZUR. 
OBIZUR temporarily replaces the inhibited endogenous Factor VIII that is needed for effective 
haemostasis. 
 
Clinical efficacy and safety 
The safety and efficacy of OBIZUR for the treatment of serious bleeding episodes in subjects with 
acquired haemophilia with autoimmune inhibitory antibodies to human Factor VIII was investigated in 
a prospective, non-randomised, open-label trial of 28 subjects (18 Caucasian, 6 Black, and 4 Asian). 
The trial included subjects presenting with life and / or limb threatening bleeding requiring 
hospitalisation. 
 
All initial bleeding episodes had a positive response to treatment at 24 hours after initial dosing as 
assessed by the primary investigator. A positive response was one where bleeding had stopped or was 
reduced, with clinical improvement or with Factor VIII activity above a pre-specified target. 
 
A positive response was observed in 95% (19/20) of subjects evaluated at 8 hours and 100% (18/18) 
at 16 hours. In addition to response to treatment, the overall treatment success was determined by the 
investigator based on his/her ability to discontinue or reduce the dose and/or dosing frequency of 
OBIZUR. A total of 24/28 (86%) had successful control (resolution) of the initial bleeding episode. Of 
those subjects treated with OBIZUR as first-line therapy, defined as no immediate previous use of 
anti-haemorrhagic agents prior to the first OBIZUR treatment, 16/17 (94%) had eventual treatment 
success reported. Eleven subjects were reported to have received anti-haemorrhagic agents (eg. 



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rFVIIa, activated prothrombin-complex concentrate, tranexamic acid) prior to first treatment with 
OBIZUR. Of these 11 subjects, eight had eventual successful treatment (73%). 
 
The median dose per injection to successfully treat the primary bleed was 133 U/kg and the median 
total dose was 1523 U/kg for a median of 6 days. The median number of daily infusions per subject 
was 1.76 (range: 0.2 to 5.6). In the initial 24 hour period, the median total dose of 493 U/kg were 
utilized in the clinical study with a median of 3 infusions. When treatment was required 
beyond 24 hours, a median total dose of 1050 U/kg were utilized with a median of 10.5 infusions 
(median dose 100 U/kg) to control a bleeding episode. 
 
Other information 
The European Medicines Agency has waived the obligation to submit the results of studies with 

OBIZUR in all subsets of the paediatric population in treatment of acquired haemophilia (see 
section 4.2 for information on paediatric use). 

 
This medicinal product has been authorised under ‘exceptional circumstances’. This means that due to 
the rarity of the disease it has not been possible to obtain complete information on this medicinal 
product. 
The European Medicines Agency will review any new information which may become available every 
year and this SmPC will be updated as necessary. 
 
5.2 Pharmacokinetic properties 
 
Pharmacokinetic data from 5 subjects with acquired haemophilia whilst in a non-bleeding state are 

presented in Table 1. 
 
Table 1: Individual pharmacokinetic data for factor VIII activity after administration of the 
final dose of OBIZUR to 5 subjects with acquired haemophilia. Subjects were in a non-bleeding 
state. Factor VIII activity was measured by the one-stage clotting assay.  

Subject Dose (U) 

Dose 
(U/kg) 

Baseline 
hFVIII 
activity 

(%) 

t½ (h) Tmax (h) 
Amax 
(%) 

AUC0-t 
(%·t) 

AUC0-∞ 
(%·t) 

 
 

1 5000 76.7 89 17 0.42 213 3124 4988 
2 2934 30.0 18 4.6 0.42 100 694 712 
3 7540 144.2 3 5.3 0.45 74 473 492 
4 9720 206.8 0 1.8 0.50 53 122 135 
5 10000 133.3 N/A 4.2 0.75 178 1583 1686 
Amax = maximum observed % activity; AUC0-t = area under the concentration-time curve from 

time 0 to the last measurable concentration; AUC0-∞ = area under the concentration-time curve 
from time 0 extrapolated to infinity; t½ = terminal half-life; Tmax = time of maximum observed % 
activity, N/A = not available. 

 
The mean recovery rate after the initial dose of 200 U/kg was 1.06 ± 0.75 U/ml per U/kg 
(range 0.10-2.61) measured with the one stage coagulation assay. 
 
Although factor VIII activity determined by the chromogenic assay is generally lower than the Factor 
VIII activity determined by the one-stage clotting assay, post-infusion Factor VIII activities in patients 
with acquired haemophilia in clinical study OBI-1-301 tended to be higher when determined with the 
chromogenic assay than with the one-stage clotting assay (see section 4.4). 
 
Inhibitory antibodies against OBIZUR were measured using a modification of the Nijmegen variation 
of the Bethesda assay method. Three subjects included in pharmacokinetic analysis had a detectable 
anti-porcine factor VIII inhibitor titre at baseline (≥ 0.6 Bethesda Units (BU)/mL). Three of the five 
subjects had no detectable anti-porcine Factor VIII titres post-treatment (< 0.6 BU/mL based on the 
last reported result), two subjects had a detectable anti-porcine Factor VIII titre (≥ 0.6 BU/mL). 
 



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The mean half-life of OBIZUR in nine evaluable subjects in the bleeding state was (about) 10 hours 
(range 2.6 to 28.6 hours). 
 
5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology or repeated dose toxicity.However, in repeated dose toxicity studies, the incidence and 
severity of glomerulopathy observed in monkeys intravenously administered OBIZUR at doses 
of 75, 225 and 750 U/kg/day tended to increase over time. 
Animal reproduction studies have not been conducted with OBIZUR. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Powder 
Polysorbate 80 
Sodium chloride 
Calcium chloride dihydrate 
Sucrose 
Tris Base 
Tris HCl 
Tri-sodium citrate dihydrate 
 
Solvent 
Sterilised water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
30 months. 
 
The reconstituted solution should be used immediately, but no longer than 3 hours after reconstitution. 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). Do not freeze. 
 
For storage conditions after reconstitution of the medicinal product, see section 6.3. 
 
6.5 Nature and contents of container 
 
One pack of OBIZUR contains 1, 5 or 10 each of the following 
 
• powder vials (type I glass) with a stopper (butyl rubber) and a flip-off seal 
• pre-filled (type I glass) syringes with a stopper (butyl rubber), a rubber tip cap and a Luer Lock 

adapter 
• fluid transfer device with an integral plastic spike 
 



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6.6 Special precautions for disposal and other handling 
 
After reconstitution, the solution is clear, colourless, free from particles and has a pH of 6.8 to 7.2. The 
osmolality of the formulation buffer ranges between 59 and 65 10% mOsm/kg H2O. 
 
Reconstituted medicinal product should be inspected visually for particulate matter and discoloration 
prior to administration. Solutions with particles or discolouration must not be administered. 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
Preparation 
 
Before starting reconstitution you will need the following: 
• Calculated number of powder vials 
• Same number of 1 mL solvent syringes and sterile vial adapters 
• Alcohol swabs 
• Large sterile syringe to contain the final volume of reconstituted product 
 
The procedures below are provided as general guidelines for the preparation and reconstitution of 
OBIZUR. Repeat following reconstitution instructions for each powder vial to be reconstituted. 
 
Reconstitution 
 
Use aseptic technique during the reconstitution procedure. 
 
1. Bring the OBIZUR powdervial and the pre-filled solvent syringe to room temperature. 
2. Remove the plastic cap from the OBIZUR powder vial (Figure A). 
3. Wipe the rubber stopper with an alcohol swab (not supplied) and allow it to dry prior to use. 
4. Peel back the cover of the vial adapter package (Figure B). Do not to touch the luer lock (tip) in 

the centre of the vial adapter. Do not remove the vial adapter from the package. 
5. Place the vial adapter package on a clean surface with the luer lock pointing up. 
6. Snap off the tamper resistant cap of the pre-filled solvent syringe (Figure C). 
7. While firmly holding the vial adapter package connect the pre-filled solvent syringe to the vial 

adapter by pushing the syringe tip down onto the luer lock in the centre of the vial adapter, and 
turning it clockwise until the syringe is secured. Do not over tighten (Figure D). 

8. Remove the plastic package (Figure E). 
9. Place the OBIZUR powder vial on a clean, flat, hard surface. Place the vial adapter over the 

OBIZUR powder vial and firmly push the filter spike of the vial adapter through the centre of 
the OBIZUR powder vial’s rubber circle until the clear plastic cap snaps onto the vial 
(Figure F). 

10. Push the plunger down to slowly inject all of the diluent from the syringe into the OBIZUR 
powder vial. 

11. Gently swirl (in a circular motion) the OBIZUR powder vial without removing the syringe until 
all of the powder is fully dissolved /reconstituted (Figure G). The reconstituted solution should 
be inspected visually for particulate matter before administration. Do not use if particulate 
matter or discoloration is observed. 

12. With one hand hold the vial and vial adapter, and with the other hand firmly grasp the barrel of 
the pre-filled solvent syringe and in a counterclockwise motion unscrew the syringe from the 
vial adapter (Figure H). 

13. Use OBIZUR immediately and within 3 hours after reconstitution when stored at room 
temperature. 

 



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Figure A Figure B Figure C Figure D 

    
Figure E Figure F Figure G Figure H 

    
 
 
Administration 
 
For intravenous injection only! 
 
• Inspect the reconstituted OBIZUR solution for particulate matter and discoloration prior to 

administration. The solution should be clear and colorless in appearance. Do not administer if 
particulate matter or discoloration is observed. 

• Do not administer OBIZUR in the same tubing or container with other medicinal products for 
injection. 

 
Using aseptic technique, administer using the following procedure: 
1. Once all vials have been reconstituted, connect a large syringe to the vial adapter by gently 

pushing the syringe tip down onto the luer lock in the centre of the vial adapter, and turning 
clockwise until the syringe is secured. 

2. Invert the vial; push the air in the syringe into the vial and withdraw the reconstituted OBIZUR 
into the syringe (Figure I). 

 
Figure I 

 
 
3. Unscrew the large syringe counterclockwise from the vial adapter, and repeat this process for all 

reconstituted vials of OBIZUR until the total volume to be administered is reached. 
4. Administer the reconstituted OBIZUR intravenously at a rate of 1 to 2 mL per minute. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Baxalta Innovations GmbH 
Industriestrasse 67 
A-1221 Vienna 
Austria 
 
 



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8. MARKETING AUTHORISATION NUMBER(S) 
 
EU/1/15/1035/001 
EU/1/15/1035/002 
EU/1/15/1035/003 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 11 November 2015 
 
 
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. 
 



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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 

 
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION 

MEASURES FOR THE MARKETING AUTHORISATION UNDER 
EXCEPTIONAL CIRCUMSTANCES 

 
 
 



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A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND 
MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer of the biological active substance 
 
Rentschler Biopharma Inc. 
27 Maple Street 
Milford 
MA 01757 
UNITED STATES 
 
Name and address of the manufacturer responsible for batch release 
 
Baxter AG 
Industriestrasse 67 
A-1221 Vienna 
AUSTRIA 
 
 
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. 

 
• Additional risk minimisation measures 
 
Prior to launch of Obizur in each Member State the Marketing Authorisation Holder (MAH) must 
agree about the content and format of the educational programme, including communication media, 
distribution modalities, and any other aspects of the programme, with the National Competent 
Authority. 



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The educational programme is aimed to minimize the risk of dose dispensing errors. 
The MAH shall ensure that in each Member State where Obizur is marketed, all healthcare 
professionals who are expected to prescribe and dispense Obizur have access to/are provided with the 
following educational package: 
• Physician educational material 
 
The physician educational material should contain: 
• The Summary of Product Characteristics 
• The healthcare professionals training material 
 
The healthcare professionals training material shall contain the following key elements: 
• Health care professional brochure including a detailed calculation of number of vials for a 

patient weighing for example 70 kg 
• An on-line video to further elaborate on the required calculation and administration of the drug 
 
 
E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES 
FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES 
 
This being a marketing authorisation under exceptional circumstances and pursuant to Article 14(8) 
of Regulation (EC) No 726/2004, the MAH shall complete, within the stated timeframe, the 
following measures: 
 

Description Due date 
To collect and analyse immediate and long-term data on clinical efficacy and safety of 
all patients with acquired haemophilia and who are treated with Obizur, the MAH must 
conduct a surveillance programme/ registry according to an agreed protocol and for an 
indefinite time. 

Annually 
within the 
annual 
reassessment 

 



15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



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A. LABELLING 



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
OBIZUR 500 U powder and solvent for solution for injection  
susoctocog alfa 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One ml of solution contains approximately 500 U of antihaemophilic factor VIII (recombinant), 
porcine sequence, susoctocog alfa after reconstitution. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: 
Polysorbate 80 
Sodium chloride 
Calcium chloride dihydrate 
Sucrose 
Tris Base 
Tris HCl 
Tri-sodium citrate dihydrate 
Read the package leaflet before use. 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
One, five, ten vials 
One, five, ten pre-filled syringes with solvent 
One, five, ten vial adapters 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
For intravenous use. 
 
Read the package leaflet before use. 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP: 
 



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9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Use immediately or within 3 hours after reconstitution. 
 
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/1/15/1035/001 
EU/1/15/1035/002 
EU/1/15/1035/003 
 
13. BATCH NUMBER 
 
Lot: 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 



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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 
 
OBIZUR 500 U powder for solution for injection 
Susoctocog alfa 
IV 
 
 
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 U 
 
 
6. OTHER 
 
Baxalta Logo 
 
 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE LABEL FOR THE SOLVENT 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Solvent for Obizur 
water for injections. 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP: 
 
 
4. BATCH NUMBER 
 
Lot: 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1 ml 
 
 
6. OTHER 
 
 



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B. PACKAGE LEAFLET 



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Package leaflet: Information for the user 
 

OBIZUR 500 U powder and solvent for solution for injection 
Susoctocog alfa 

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

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

even if their signs of illness are the same as yours. 
- If you get any side effects, talk to your doctor. This includes any possible side effects not listed 

in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What OBIZUR is and what it is used for 
2. What you need to know before you use OBIZUR 
3. How to use OBIZUR 
4. Possible side effects 
5. How to store OBIZUR 
6. Contents of the pack and other information 
 
 
1. What OBIZUR is and what it is used for 
 
OBIZUR contains the active substance susoctocog alfa, antihaemophilic Factor VIII, porcine 
sequence. Factor VIII is necessary for the blood to form clots and stop bleedings. 
In patients with acquired haemophilia, FVIII is not working properly because the patient has 
developed antibodies to his own Factor VIII which neutralize this blood clotting factor. 
 
OBIZUR is used for the treatment of bleeding episodes in adults with acquired haemophilia (a 
bleeding disorder caused by lack of Factor VIII activity due to antibody development). These 
antibodies have less neutralizing effect against OBIZUR than against human Factor VIII. 
 
OBIZUR restores this missing Factor VIII activity and helps blood to form clots at the site of bleeding. 
 
 
2. What you need to know before you use OBIZUR 
 
The product is for in-patient administration only. It requires clinical supervision of the bleeding status 
of the patient. 
 
Do not use OBIZUR: 
- if you are allergic to susoctocog alfa or any of the other ingredients of this medicine (listed in 

section 6) 
- if you are allergic to hamster proteins (trace amounts may be present in Obizur arising from the 

manufacturing process) 
 
If you are not sure, talk to your doctor before using this medicine. 
 
Warnings and precautions 
Talk to your doctor before using OBIZUR. 



23 

 
There is a rare chance that you may experience an allergic reaction to OBIZUR. You should be aware 
of the early signs of allergic reactions (see section 4 for signs and symptoms). If any of these 
symptoms occur, the injection should be stopped. Severe symptoms, including difficulty in breathing 
and (near) fainting, require emergency treatment. 
 
Patients developing inhibitory antibodies to OBIZUR 
Your doctor may check if you have inhibitory antibodies to porcine Factor VIII. 
Your doctor will check your blood Factor VIII to confirm that enough Factor VIII is being given to 
you. Your doctor will also check if the bleeding is adequately controlled. 
 
Talk to your doctor if you have had a cardiovascular disease in the past or if you have a known risk of 
thrombosis (diseases from blood clots in normal vasculature), because the possiblity of developing 
thromboembolic diseases at high and sustained blood Factor VIII levels cannot be excluded. 
 
Name and batch number 
It is strongly recommended that every time OBIZUR is used, the name and batch number of the 
medicine are recorded by the medical professional to maintain a link between your treatment and the 
batch of the medicine. 
 
Use in children and adolescents 
OBIZUR is not currently approved for treatment of patients under 18 years of age, in whom acquired 
haemophilia is rare. 
 
Other medicines and OBIZUR 
Tell your doctor if you are using, have recently used or might use any other medicines. No interactions 
of OBIZUR with other medicines are known. 
 
Pregnancy and breast-feeding 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor for advice before using this medicine. 
 
Driving and using machines 
OBIZUR has no influence on your ability to drive and use machines. 
 
OBIZUR contains sodium 
This medicine contains 4.4 mg sodium per milliliter once it is made up. 
 
Talk to your doctor if you are on a controlled sodium diet. 
 
 
3. How to use OBIZUR 
 
Treatment with OBIZUR will be conducted by a doctor who is experienced in the care of patients with 
haemophilia (bleeding disorders). 
 
Your doctor will calculate your dose of OBIZUR (in units or U) depending on your condition and 
body weight. The frequency and duration of administration will depend on how well OBIZUR is 
working for you. Usually, the replacement therapy with OBIZUR is a temporary treatment until 
bleeding is resolved or the antibodies against your own Factor VIII are eradicated. 
 
The recommended first dose is 200 U per kilogram bodyweight given by intravenous injection. 
 
Your doctor will measure your Factor VIII activity regularly to decide the subsequent dose and 
frequency of OBIZUR. 
The bleeding will usually respond within the first 24 hours, your doctor will adjust the dose and 
duration of OBIZUR until the bleeding stopped. 



24 

The total volume of reconstituted OBIZUR should be administered at a rate of 1 to 2 mL per minute. 
 
Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure. 
 
If you use more OBIZUR than you should 
Always use OBIZUR exactly as your doctor has told you. If you use more OBIZUR than 

recommended, tell your doctor as soon as possible. 
 
If you forget to use OBIZUR 
Do not use a double dose to make up for a forgotten dose. You should contact your doctor if you 
missed a dose and do not know how to compensate for this. 
 
If you stop using OBIZUR 
Do not stop using OBIZUR without consulting your doctor. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
If severe and sudden allergic reactions occur, the injection must be stopped immediately. You must 
contact your doctor immediately if you have any of the following early symptoms: 
 
- Swelling of lips and tongue 
- Burning and stinging at the injection site 
- Chills, flushing 
- Hives, generalised itching 
- Headache, low blood pressure 
- Lethargy, sickness, restlessness 
- Rapid beating of the heart, tightness of the chest 
- Tingling, vomiting 
- Wheezing 
 
Common side effects (may affect up to 1 in 10 people) 
- Development of antibodies against the medicine 
 
Reporting of side effects 
If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this 
leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. 
By reporting side effects, you can help provide more information on the safety of this medicine. 
 
 
5. How to store OBIZUR 
 
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 carton, on the vial and on the 
pre-filled syringe after EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
 
Use the reconstituted solution immediately but no longer than 3 hours once the powder is completely 
dissolved. 



25 

 
After reconstitution the solution should be clear and colourless. 
Do not administer if particulate matter or discoloration is found. 
 
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 OBIZUR contains 
- The active substance is susoctocog alfa (antihaemophilic Factor VIII, porcine sequence 

produced by recombinant DNA technology). Each powder vial contains 500 U susoctocog alfa. 
- The other ingredients in the powder are polysorbate 80, sodium chloride (see also section 2), 

calcium chloride dihydrate, sucrose, Tris base, Tris HCl, Tri-sodium citrate dihydrate. 
- The solvent is 1 ml sterilised water for injections. 
 
What OBIZUR looks like and contents of the pack 
One pack contains 1, 5 or 10 of the following: 
- glass vial of OBIZUR 500 U white, friable powder with a rubber stopper and a flip-off seal 
- pre-filled glass syringe of 1 ml sterilised water for injections with a rubber tip cap and a Luer 

Lock adapter 
- fluid transfer device with an integral plastic spike 
 
Marketing Authorisation Holder and Manufacturer 
 
Marketing authorisation holder 
Baxalta Innovations GmbH 
Industriestrasse 67 
A-1221 Vienna 
Austria 
Tel.: +44(0)1256 894 959 
E-mail: medinfoEMEA@shire.com 
 
Manufacturer 
Baxter AG 
Industriestrasse 67 
A-1221 Vienna 
Austria 
 
 
This leaflet was last revised in. 
 
This medicine has been authorised under ‘exceptional circumstances’. This means that because of the 
rarity of this disease it has been impossible to get complete information on this medicine. 
The European Medicines Agency will review any new information on this medicine every year and 
this leaflet will be updated as necessary. 
 
Other sources of information 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu <, and on the website of {name of MS Agency (link)}>. <There are also 
links to other websites about rare diseases and treatments. 
 
<This leaflet is available in all EU/EEA languages on the European Medicines Agency website.> 
 
--------------------------------------------------------------------------------------------------------------------------- 



26 

 
The following information is intended for healthcare professionals only: 
 
INSTRUCTIONS FOR PREPARATION AND ADMINISTRATION 
 
Preparation 
 
Before starting reconstitution you will need the following: 
• Calculated number of powder vials 
• Same number of 1 mL solvent syringes and sterile vial adapters 
• Alcohol swabs 
• Large sterile syringe to contain the final volume of reconstituted product 
 
The procedures below are provided as general guidelines for the preparation and reconstitution of 
OBIZUR. Repeat following reconstitution instructions for each powder vial to be reconstituted. 
 
Reconstitution 
 
Use aseptic technique during the reconstitution procedure. 
 
1. Bring the OBIZUR powder vial and pre-filled diluent solvent syringe to room temperature. 
2. Remove the plastic cap from the OBIZUR powder vial (Figure A). 
3. Wipe the rubber stopper with an alcohol swab (not supplied) and allow it to dry prior to use. 
4. Peel back the cover of the vial adapter package (Figure B). Do not to touch the luer lock (tip) in 

the centre of the vial adapter. Do not remove the vial adapter from the package. 
5. Place the vial adapter package on a clean surface with the luer lock pointing up. 
6. Snap off the tamper resistant cap of the pre-filled solvent syringe (Figure C). 
7. While firmly holding the vial adapter package connect the pre-filled solvent syringe to the vial 

adapter by pushing the syringe tip down onto the luer lock in the centre of the vial adapter, and 
turning it clockwise until the syringe is secured. Do not over tighten (Figure D). 

8. Remove the plastic package (Figure E). 
9. Place the OBIZUR powder vial on a clean, flat, hard surface. Place the vial adapter over the 

OBIZUR powder vial and firmly push the filter spike of the vial adapter through the centre of 
the OBIZUR powder vial’s rubber circle until the clear plastic cap snaps onto the vial 
(Figure F). 

10. Push the plunger down to slowly inject all of the diluent from the syringe into the OBIZUR 
powder vial. 

11. Gently swirl (in a circular motion) the OBIZUR powder vial without removing the syringe until 
all of the powder is fully dissolved /reconstituted (Figure G). The reconstituted solution should 
be inspected visually for particulate matter before administration. Do not use if particulate 
matter or discoloration is observed. 

12. With one hand hold the powder vial and vial adapter, and with the other hand firmly grasp the 
barrel of the pre-filled solvent syringe and in a counterclockwise motion unscrew the syringe 
from the vial adapter (Figure H). 

13. Use OBIZUR immediately and within 3 hours after reconstitution when stored at room 
temperature. 



27 

 
 
Figure A Figure B Figure C Figure D 

    
Figure E Figure F Figure G Figure H 

    
 
Administration 
 
For intravenous injection only! 
 
• Inspect the reconstituted OBIZUR solution for particulate matter and discoloration prior to 

administration. The solution should be clear and colorless in appearance. Do not administer if 
particulate matter or discoloration is observed. 

• Do not administer OBIZUR in the same tubing or container with other medicinal products for 
injection. 

 
Using aseptic technique, administer using the following procedure: 
1. Once all vials have been reconstituted, connect a large syringe to the vial adapter by gently 

pushing the syringe tip down onto the luer lock in the centre of the vial adapter, and turning 
clockwise until the syringe is secured. 

2. Invert the vial; push the air in the syringe into the vial and withdraw the reconstituted OBIZUR 
into the syringe (Figure I). 

 
Figure I 

 
 
3. Unscrew the large syringe counterclockwise from the vial adapter, and repeat this process for all 

reconstituted vials of OBIZUR until the total volume to be administered is reached. 
4. Administer the reconstituted OBIZUR intravenously at a rate of 1 to 2 mL per minute. 
 
The required initial dose of Obizur for a patient is calculated using the following formula: 

Initial dose (U/kg) ÷ Product strength (U/vial) × Body weight (kg) = Number of vials 
 
e.g. for a 70 kg subject the number of vials for an initial dose will be calculated as follows: 

200 U/kg ÷ 500 U/vial × 70 kg = 28 vials 
 



28 

Dosing 
 
The recommended initial dose is 200 U per kilogram bodyweight, given by injection. 
 

Type of Bleeding Target Factor VIII 
Trough Activity 

(Units per dL or % of 
normal) 

Initial Dose 
(Units per 

kg) 

Subsequent 
Dose 

Frequency and 
Duration of 
Subsequent 

Dosing 
Mild and moderate 
superficial 
muscle/no 
neurovascular 
compromise and 
joint bleeding 

>50% 

200 

Titrate 
subsequent 
doses based on 
clinical 
response and 
to maintain 
target Factor 
VIII trough 
activity  

Dose 
every 4 to 12 hours, 
frequency may be 
adjusted based on 
clinical response 
and measured 
Factor VIII activity Major moderate to 

severe 
intramuscular, 
retroperitoneal, 
gastrointestinal, 
intracranial bleeding 

>80% 

 
 

 
 


	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
	E. SPECIFIC OBLIGATION TO COMPLETE POST-AUTHORISATION MEASURES FOR THE MARKETING AUTHORISATION UNDER EXCEPTIONAL CIRCUMSTANCES
	A. LABELLING
	B. PACKAGE LEAFLET