2. Qualitative and Quantitative Composition

Each powder vial contains nominally 500 Uunits of B domain deleted antihaemophilic Ffactor VIII (recombinant (rDNA), porcine sequence, susoctocog alfa.

OBIZUR contains approximately 500 U/ml of susoctocog alfa after reconstitution.

OBIZUR (antihaemophilic Ffactor VIII (recombinant rDNA), 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 foetal bovine serum.

Excipient(s) with known effect

Each vial contains  4.4 4.6 mg (198 mM) sodium per ml of reconstituted solution.

4.2. Posology and method of administration

Addition of following:

Treatment monitoring

During the course of treatment, appropriate determination of factor VIII levels is advised to guide the dose to be administered and the frequency of repeated infusions. Individual patients may vary in their response to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight may require adjustment in underweight or overweight patients.

In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable.

When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining factor VIII activity in patients’ blood samples, plasma factor VIII activity results can be significantly affected by both the type of aPTT reagent and the reference standard used in the assay. Also there can be significant discrepancies between assay results obtained by aPTT-based one stage clotting assay and the chromogenic assay according to Ph. Eur. This is of importance particularly when changing the laboratory and/or reagents used in the assay.

Paediatric population

The safety and efficacy of OBIZUR Use in children and adolescents aged below 18 years with congenital haemophilia with inhibitors or in rare cases of acquired haemophilia is currently not approved have not yet been established. No data are available.

4.3 Contraindications

Known anaphylactic reactions Hypersensitivity 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

Traceability

In order to improve traceability of biological medicinal products, the name and the batch number of the administered medicinal product should be clearly recorded.

Hypersensitivity

(…)The medicinal product contains trace amounts of hamster proteins.

Development of inhubitory antibodies Inhibitors

Cardiovascular events

In patients with existing cardiovascular risk factors, substitution therapy with FVIII may increase the cardiovascular risk.

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

OBIZUR contains 4.6 mg sodium in 1 mL of reconstituted solution in each vial, equivalent to 0.23% of the WHO recommended maximum daily intake of 2 g sodium for an adult.  Multiple vials must be taken per dose e.g A 70 kg patient using the recommended 200 U/kg dose would require 28 vials which results in a sodium intake of 128.8 mg per treatment.  This is equivalent to 6.44% of the WHO recommended maximum daily intake of 2 g of sodium for an adult.

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.

4.8          Undesirable effects

Patients with acquired haemophilia may develop inhibitory antibodies to porcine Ffactor VIII. Inhibitory antibodies, including anamnestic responses, may result in a lack of response to OBIZUR.

Tabulated list of adverse reactions:

The table presented below is according to the MedDRA system organ classification (SOC and Ppreferred Tterm Llevel). In the clinical trial study (…) subjects patients were evaluable for safety.

5.1          Pharmacodynamic properties

Other information replaced with Paediatric population

6.1       List of excipients

Powder

Polysorbate 80

Sodium chloride

Calcium chloride dihydrate

Sucrose

Trometamol hydrochloride Tris Base

Tris HCl

Tri sSodium citrate dihydrate

Solvent

Sterilised wWater for injections

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 coated with FluroTec®) and a flip off seal;

•              pre filled (type I glass) syringes with a stopper (bromobutyl rubber coated with FluroTec® foil on the contact side), a bromobutyl rubber tip cap and a Luer Llock adapter

9. Data of latest renewal

10 Date of revision of the text

16^th  November 2020

16^th November 2020

2. Qualitative and Quantitative Composition

Each powder vial contains nominally 500 Uunits of B domain deleted antihaemophilic Ffactor VIII (recombinant (rDNA), porcine sequence, susoctocog alfa.

OBIZUR contains approximately 500 U/ml of susoctocog alfa after reconstitution.

OBIZUR (antihaemophilic Ffactor VIII (recombinant rDNA), 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 foetal bovine serum.

Excipient(s) with known effect

Each vial contains  4.4 4.6 mg (198 mM) sodium per ml of reconstituted solution.

4.2. Posology and method of administration

Addition of following:

Treatment monitoring

During the course of treatment, appropriate determination of factor VIII levels is advised to guide the dose to be administered and the frequency of repeated infusions. Individual patients may vary in their response to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight may require adjustment in underweight or overweight patients.

In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable.

When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining factor VIII activity in patients’ blood samples, plasma factor VIII activity results can be significantly affected by both the type of aPTT reagent and the reference standard used in the assay. Also there can be significant discrepancies between assay results obtained by aPTT-based one stage clotting assay and the chromogenic assay according to Ph. Eur. This is of importance particularly when changing the laboratory and/or reagents used in the assay.

Paediatric population

The safety and efficacy of OBIZUR Use in children and adolescents aged below 18 years with congenital haemophilia with inhibitors or in rare cases of acquired haemophilia is currently not approved have not yet been established. No data are available.

4.3 Contraindications

Known anaphylactic reactions Hypersensitivity 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

Traceability

In order to improve traceability of biological medicinal products, the name and the batch number of the administered medicinal product should be clearly recorded.

Hypersensitivity

(…)The medicinal product contains trace amounts of hamster proteins.

Development of inhubitory antibodies Inhibitors

Cardiovascular events

In patients with existing cardiovascular risk factors, substitution therapy with FVIII may increase the cardiovascular risk.

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

OBIZUR contains 4.6 mg sodium in 1 mL of reconstituted solution in each vial, equivalent to 0.23% of the WHO recommended maximum daily intake of 2 g sodium for an adult.  Multiple vials must be taken per dose e.g A 70 kg patient using the recommended 200 U/kg dose would require 28 vials which results in a sodium intake of 128.8 mg per treatment.  This is equivalent to 6.44% of the WHO recommended maximum daily intake of 2 g of sodium for an adult.

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.

4.8          Undesirable effects

Patients with acquired haemophilia may develop inhibitory antibodies to porcine Ffactor VIII. Inhibitory antibodies, including anamnestic responses, may result in a lack of response to OBIZUR.

Tabulated list of adverse reactions:

The table presented below is according to the MedDRA system organ classification (SOC and Ppreferred Tterm Llevel). In the clinical trial study (…) subjects patients were evaluable for safety.

5.1          Pharmacodynamic properties

Other information replaced with Paediatric population

6.1       List of excipients

Powder

Polysorbate 80

Sodium chloride

Calcium chloride dihydrate

Sucrose

Trometamol hydrochloride Tris Base

Tris HCl

Tri sSodium citrate dihydrate

Solvent

Sterilised wWater for injections

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 coated with FluroTec®) and a flip off seal;

•              pre filled (type I glass) syringes with a stopper (bromobutyl rubber coated with FluroTec® foil on the contact side), a bromobutyl rubber tip cap and a Luer Llock adapter

9. Data of latest renewal

10 Date of revision of the text

16^th  November 2020

16^th November 2020

2. Qualitative and Quantitative Composition

Each powder vial contains nominally 500 Uunits of B domain deleted antihaemophilic Ffactor VIII (recombinant (rDNA), porcine sequence, susoctocog alfa.

OBIZUR contains approximately 500 U/ml of susoctocog alfa after reconstitution.

OBIZUR (antihaemophilic Ffactor VIII (recombinant rDNA), 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 foetal bovine serum.

Excipient(s) with known effect

Each vial contains  4.4 4.6 mg (198 mM) sodium per ml of reconstituted solution.

4.2. Posology and method of administration

Addition of following:

Treatment monitoring

During the course of treatment, appropriate determination of factor VIII levels is advised to guide the dose to be administered and the frequency of repeated infusions. Individual patients may vary in their response to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight may require adjustment in underweight or overweight patients.

In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable.

When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining factor VIII activity in patients’ blood samples, plasma factor VIII activity results can be significantly affected by both the type of aPTT reagent and the reference standard used in the assay. Also there can be significant discrepancies between assay results obtained by aPTT-based one stage clotting assay and the chromogenic assay according to Ph. Eur. This is of importance particularly when changing the laboratory and/or reagents used in the assay.

Paediatric population

The safety and efficacy of OBIZUR Use in children and adolescents aged below 18 years with congenital haemophilia with inhibitors or in rare cases of acquired haemophilia is currently not approved have not yet been established. No data are available.

4.3 Contraindications

Known anaphylactic reactions Hypersensitivity 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

Traceability

In order to improve traceability of biological medicinal products, the name and the batch number of the administered medicinal product should be clearly recorded.

Hypersensitivity

(…)The medicinal product contains trace amounts of hamster proteins.

Development of inhubitory antibodies Inhibitors

Cardiovascular events

In patients with existing cardiovascular risk factors, substitution therapy with FVIII may increase the cardiovascular risk.

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

OBIZUR contains 4.6 mg sodium in 1 mL of reconstituted solution in each vial, equivalent to 0.23% of the WHO recommended maximum daily intake of 2 g sodium for an adult.  Multiple vials must be taken per dose e.g A 70 kg patient using the recommended 200 U/kg dose would require 28 vials which results in a sodium intake of 128.8 mg per treatment.  This is equivalent to 6.44% of the WHO recommended maximum daily intake of 2 g of sodium for an adult.

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.

4.8          Undesirable effects

Patients with acquired haemophilia may develop inhibitory antibodies to porcine Ffactor VIII. Inhibitory antibodies, including anamnestic responses, may result in a lack of response to OBIZUR.

Tabulated list of adverse reactions:

The table presented below is according to the MedDRA system organ classification (SOC and Ppreferred Tterm Llevel). In the clinical trial study (…) subjects patients were evaluable for safety.

5.1          Pharmacodynamic properties

Other information replaced with Paediatric population

6.1       List of excipients

Powder

Polysorbate 80

Sodium chloride

Calcium chloride dihydrate

Sucrose

Trometamol hydrochloride Tris Base

Tris HCl

Tri sSodium citrate dihydrate

Solvent

Sterilised wWater for injections

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 coated with FluroTec®) and a flip off seal;

•              pre filled (type I glass) syringes with a stopper (bromobutyl rubber coated with FluroTec® foil on the contact side), a bromobutyl rubber tip cap and a Luer Llock adapter

9. Data of latest renewal

10 Date of revision of the text

16^th  November 2020

16^th November 2020

Section

Changes

4.4     Special warnings and precautions for use

Addition of the following text:

Anamnestic reactions with rise in human factor VIII and/or porcine factor VIII inhibitors have also been reported in patients treated with OBIZUR. These anamnestic rises may result in lack of response to OBIZUR.  

4.8     Undesirable effects 

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 HPRA Pharmacovigilance, Website: www.hpra.ie

HPRA Pharmacovigilance

Earlsfort Terrace

Dublin 2

Ireland

Tel: +353 1 676 4971

Fax: +353 1 676 2517

Website: www.hpra.ie

E-mail: medsafety@hpra.ie

10 Date of revision of the text

17 September 2020