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Advate (octocog alfa) – Package leaflet - B02BD02

Updated on site: 05-Oct-2017

Package leaflet: Information for the user

ADVATE 250 IU powder and solvent for solution for injection

ADVATE 500 IU powder and solvent for solution for injection

ADVATE 1000 IU powder and solvent for solution for injection

ADVATE 1500 IU powder and solvent for solution for injection

ADVATE 2000 IU powder and solvent for solution for injection

ADVATE 3000 IU powder and solvent for solution for injection

Octocog alfa (recombinant human coagulation factor VIII)

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 ADVATE is and what it is used for

2.What you need to know before you use ADVATE

3.How to use ADVATE

4.Possible side effects

5.How to store ADVATE

6.Contents of the pack and other information

1.What ADVATE is and what it is used for

ADVATE contains the active substance octocog alfa, human coagulation factor VIII produced by recombinant DNA technology. Factor VIII is necessary for the blood to form clots and stop bleedings. In patients with haemophilia A (inborn lack of factor VIII), it is missing or not working properly.

ADVATE is used for the treatment and prevention of bleeding in patients of all age groups with haemophilia A (an inherited bleeding disorder caused by lack of factor VIII).

ADVATE is prepared without the addition of any human- or animal-derived protein in the entire manufacturing process.

2. What you need to know before you use ADVATE

Do not use ADVATE

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

-if you are allergic to mouse or hamster proteins

If you are unsure about this, ask your doctor.

Warnings and precautions

Talk to your doctor before using ADVATE. You should tell your doctor if you have been previously treated with Factor VIII products, especially if you developed inhibitors, since there might be a higher risk that it happens again. Inhibitors are blocking antibodies against factor VIII that reduce the efficacy

of ADVATE to prevent or control bleeding. Development of inhibitors is a known complication in the treatment of haemophilia A. If your bleeding is not controlled with ADVATE, tell your doctor immediately.

There is a rare risk that you may experience an anaphylactic reaction (a severe, sudden allergic reaction) to ADVATE. You should be aware of the early signs of allergic reactions such as rash, hives, wheals, generalised itching, swelling of lips and tongue, difficulty in breathing, wheezing, tightness in the chest, general feeling of being unwell, and dizziness. These symptoms can constitute an early symptom of an anaphylactic shock, manifestations of which may additionally include extreme dizziness, loss of consciousness, and extreme difficulty in breathing.

If any of these symptoms occur, stop the injection immediately and contact your doctor. Severe symptoms, including difficulty in breathing and (near) fainting, require prompt emergency treatment.

Patients developing Factor VIII inhibitors

If your plasma Factor VIII fails to reach expected levels with ADVATE, or if bleeding is not adequately controlled, it could be due to the development of Factor VIII inhibitors. This will be checked by your doctor. You might need a higher dose of ADVATE or even a different product to control bleedings. Do not increase the total dose of ADVATE to control your bleeding without consulting your doctor.

Children and adolescents

The listed warnings and precautions apply to both adults and children (from 0 to 18 years of age).

Other medicines and ADVATE

Tell your doctor if you are using, have recently used or might use any other medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.

Driving and using machines

ADVATE has no influence on your ability to drive or to use machines.

ADVATE contains sodium

This medicine contains 0.45 mmol sodium (10 mg) per vial. To be taken into consideration by patients on a controlled sodium diet.

3.How to use ADVATE

Treatment with ADVATE will be started by a doctor who is experienced in the care of patients with haemophilia A.

Your doctor will calculate your dose of ADVATE (in international units or IU) depending on your condition and body weight, and on whether it is used for prevention or treatment of bleeding. The frequency of administration will depend on how well ADVATE is working for you. Usually, the replacement therapy with ADVATE is a life-long treatment.

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

Prevention of bleeding

The usual dose of octocog alfa is 20 to 40 IU per kg body weight, administered every 2 to 3 days. However, in some cases, especially in younger patients, more frequent injections or higher doses may be necessary.

Treatment of bleeding

The dose of octocog alfa is calculated depending on your body weight and the factor VIII levels to be achieved. The target factor VIII levels will depend on the severity and location of the bleeding.

Dose (IU) = body weight (kg) x desired Factor VIII rise (% of normal) x 0.5

If you have the impression that the effect of ADVATE is insufficient, talk to your doctor.

Your doctor will perform appropriate laboratory tests to make sure that you have adequate Factor VIII levels. This is particularly important if you are having major surgery.

Use in children and adolescents (from 0 to 18 years of age)

For the treatment of bleeding the dosing in children does not differ from adult patients. For the prevention of bleeding in children under the age of 6, doses of 20 to 50 IU per kg body weight 3 to 4 times weekly are recommended. The administration of ADVATE in children (intravenously) does not differ from the administration in adults. A central venous access device (CVAD) may become necessary to allow frequent infusions of factor VIII products.

How ADVATE is given

ADVATE is usually injected into a vein (intravenously) by your doctor or nurse. You or someone else might also administer ADVATE as an injection, but only after receiving adequate training. Detailed instructions for self-administration are given at the end of this package leaflet.

If you use more ADVATE than you should

Always take ADVATE exactly as your doctor has told you. You should check with your doctor if you are not sure. If you inject more ADVATE than recommended, tell your doctor as soon as possible.

If you forget to use ADVATE

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 ADVATE

Do not stop using ADVATE 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, sudden allergic reactions (anaphylactic) occur, the injection must be stopped immediately. You must contact your doctor immediately if you have any of the following early symptoms of allergic reactions:

-rash, hives, wheals, generalised itching,

-swelling of lips and tongue,

-difficulty in breathing, wheezing, tightness in the chest,

-general feeling of being unwell,

-dizziness and loss of consciousness.

Severe symptoms, including difficulty in breathing and (nearly) fainting, require prompt emergency treatment.

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

Factor VIII inhibitors, headache and fever.

Uncommon side effects (may affect up to 1 in 100 people)

dizziness, flu, fainting, abnormal heartbeat, red itchy bumps on the skin, chest discomfort, injection site bruise, injection site reaction, itching, increased sweating, unusual taste in the mouth, hot flushes, migraines, memory impairment, chills, diarrhoea, nausea, vomiting, shortness of breath, sore throat, infection of the lymphatic vessels, whitening of skin, eye inflammation, rashes, excessive sweating, foot and leg swelling, reduced percentage of red blood cells, increase in a type of white blood cells (monocytes), and pain in the upper abdomen or lower chest.

Related to surgery

catheter-related infection, decreased red cell blood count, swelling of limbs and joints, prolonged bleeding after drain removal, decreased Factor VIII level and post-operative bruise.

Related to central venous access devices (CVAD)

catheter-related infection, systemic infection and local blood clot at the catheter site.

Side effects with unknown frequency (frequency cannot be estimated from the available data) potentially life-threatening reactions (anaphylaxis) and other allergic reactions (hypersensitivity), general disorders (tiredness, lack of energy).

Additional side effects in children

Other than the development of inhibitors in previously untreated paediatric patients (PUPs), and catheter-related complications, no age-specific differences in side effects were noted in the clinical studies.

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 ADVATE

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

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

During the shelf life the powder vial may be kept at room temperature (up to 25 °C) for a single period not exceeding 6 months. In this case, this medicine expires at the end of this 6 month period or the expiration date printed on the product vial, whichever is earlier. Please record the end of the 6 months storage at room temperature on the product carton. The product may not be returned to refrigerated storage after storage at room temperature.

Keep the vial in the outer carton in order to protect from light.

This product is for single use only. Discard any unused solution appropriately.

Use the product immediately once the powder is completely dissolved.

Do not refrigerate the solution after preparation.

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 protect the environment.

6. Contents of the pack and other information

What ADVATE contains

-The active substance is octocog alfa (human coagulation Factor VIII produced by recombinant DNA technology). Each powder vial contains nominally 250, 500, 1000, 1500, 2000, or

3000 IU octocog alfa.

-The other ingredients are mannitol, sodium chloride, histidine, trehalose, calcium chloride, trometamol, polysorbate 80, and glutathione (reduced).

Solvent vial: 5 ml sterilised water for injections

What ADVATE looks like and contents of the pack

ADVATE is a white to off-white friable powder. After reconstitution, the solution is clear, colourless and free from foreign particles.

Each pack also contains a device for reconstitution (BAXJECT II).

Marketing Authorisation Holder

Baxter AG

Industriestrasse 67

A-1221 Vienna

Manufacturers

Baxalta Belgium Manufacturing SA

Boulevard René Branquart 80

B-7860 Lessines

Belgium

Baxter SA

Boulevard René Branquart 80

B-7860 Lessines

Belgium

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Baxalta Belgium SPRL

UAB ″Baxter Lithuania″

Tél/Tel: +32 2 892 62 00

Tel: +370 5 269 16 90 / +370 5 252 71 00

България

Luxembourg/Luxemburg

Бакстер България ЕООД

Baxalta Belgium SPRL

тел.: +359 2 9808482

Tél/Tel: +32 2 892 62 00

Česká republika

Magyarország

Baxter Czech spol.s.r.o.

Baxter Hungary Kft.

Tel.: +420 225774111

Tel.: +36 1 202 1980

Danmark

Malta

Baxalta Denmark A/S

Baxalta UK Limited

Tlf: +45 32 70 12 00

Tel.: +44 1 635 798 777

Deutschland

Nederland

Baxalta Deutschland GmbH

Baxalta Netherlands B.V.

Tel: +49 89 262077-011

Tel: +31 30 799 27 77

Eesti

Norge

OÜ Baxter Estonia

Baxalta Norway AS

Tel.: +372 6 515 120

Tlf: +47 22 585 000

Ελλάδα

Österreich

Baxter (Hellas) Ε.Π.Ε.

Baxalta Österreich GmbH

Τηλ.: +30 210 28 80 000

España

Polska

Baxalta Spain S.L.

Baxter Polska Sp. z o.o.

Tel: +34 91 790 42 22

Tel.: +48 22 4883 777

France

Portugal

Baxalta France S.A.S.

Baxalta Portugal, Unipessoal, Lda.

Tél: +33 1 70 96 06 00

Tel: +351 21 122 03 00

Hrvatska

România

Baxter d.o.o.

FARMACEUTICA REMEDIA SA

Tel: +386 1 420 16 80

Tel.: +40 21 321 16 40

Ireland

Slovenija

Baxalta UK Limited

Baxter d.o.o.

Tel: +44 1 635 798 777

Tel.: +386 1 420 16 80

Ísland

Slovenská republika

Lyfjaver ehf.

Baxter Slovakia s.r.o.

Sími: +354 533 6100

Tel: +421 2 3210 1150

Italia

Suomi/Finland

Baxalta Italy S.r.l.

Baxalta Finland Oy

Tel: +39 06 45224 600

Puh/Tel: +358 201478200

Κύπρος

Sverige

Baxter (Hellas) Ε.Π.Ε.

Baxalta Sweden AB

Τηλ.: +30 210 28 80 000

Tel: +46 8 50 53 26 00

Latvija

United Kingdom

SIA BAXTER Latvia

Baxalta UK Limited

Tel.: +371 67 784 784

Tel: +44 1 635 798 777

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

Instructions for preparation and administration

Aseptic technique is required during preparation of the solution and administration.

Use only the sterilised water for injections and the reconstitution device for preparation of the solution that are provided with each package of ADVATE. ADVATE must not be mixed with other medicinal products or solvents.

It is strongly recommended that every time ADVATE is administered, the name and batch number of the product are recorded.

Instructions for reconstitution

Do not use after the expiry date stated on the labels and carton.

Do not use if the BAXJECT II device, its sterile barrier system or its packaging is damaged or shows any sign of deterioration as indicated by the symbol: .

Do not refrigerate the solution after preparation.

1.If the product is still stored in a refrigerator, take both the ADVATE powder and solvent vials from the refrigerator and let them reach room temperature (between 15 °C and 25 °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. Do not use if the BAXJECT II device, its sterile barrier system or its packaging is damaged or shows any sign of deterioration.

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.For reconstitution only the sterilised water for injections and the reconstitution device provided in the pack should be used. 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 ADVATE powder stopper. The vacuum will draw the solvent into the ADVATE powder vial (Fig. c).

8.Swirl gently until all material is dissolved. Be sure that the ADVATE powder is completely dissolved, otherwise not all reconstituted solution will pass through the device filter. The product dissolves rapidly (usually in less than 1 minute). After reconstitution the solution should be clear, colourless and free from foreign particles.

Fig. a

Fig. b

Fig. c

Instructions for injection

For administration the use of a luer-lock syringe is required.

Important note:

Do not try to administer the injection unless you have received special training from your doctor or nurse.

Inspect the prepared solution for particulate matter and discoloration prior to administration (the solution should be clear, colourless and free from foreign particles).

Do not use ADVATE if the solution is not fully clear or not completely dissolved.

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 and inject the reconstituted solution into a vein. The solution should be administered slowly, at a rate as determined by the patient’s comfort level, not to exceed 10 ml per minute. (See Section 4 “Possible side effects”).

5.Discard any unused solution appropriately.

Fig. d

Fig. e

-------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

On demand treatment

In case of the following haemorrhagic events, the factor VIII 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.

The dose and frequency of administration should be adapted to the clinical response in the individual case. Under certain circumstances (e.g. presence of a low-titre inhibitor), doses larger than those calculated using the formula may be necessary.

Degree of haemorrhage/type of

Factor VIII level

Frequency of doses (hours)/duration

surgical procedure

required (% or IU/dl)

of therapy (days)

Haemorrhage

 

 

Early haemarthrosis, muscle

20 – 40

Repeat injections every 12 to 24 hours

bleeding or oral bleeding.

 

(8 to 24 hours for patients under the age

 

 

of 6) for at least 1 day, until the

 

 

bleeding episode, as indicated by pain,

 

 

is resolved or healing is achieved.

More extensive haemarthrosis,

30 – 60

Repeat injections every 12 to 24 hours

muscle bleeding or haematoma.

 

(8 to 24 hours for patients under the age

 

 

of 6) for 3 – 4 days or more until pain

 

 

and acute disability are resolved.

Life-threatening haemorrhages.

60 – 100

Repeat injections every 8 to 24 hours

 

 

(6 to 12 hours for patients under the age

 

 

of 6) until threat is resolved.

Degree of haemorrhage/type of

Factor VIII level

Frequency of doses (hours)/duration

surgical procedure

required (% or IU/dl)

of therapy (days)

Surgery

 

 

Minor

30 – 60

Every 24 hours (12 to 24 hours for

Including tooth extraction.

 

patients under the age of 6), at

 

 

least 1 day, until healing is achieved.

Major

80 – 100

Repeat injections every 8 to 24 hours

 

(pre- and postoperative)

(6 to 24 hours for patients under the age

 

 

of 6) until adequate wound healing,

 

 

then continue therapy for at least

 

 

another 7 days to maintain a factor VIII

 

 

activity of 30% to 60% (IU/dl).

Package leaflet: Information for the user

ADVATE 250 IU powder and solvent for solution for injection

ADVATE 500 IU powder and solvent for solution for injection

ADVATE 1000 IU powder and solvent for solution for injection

ADVATE 1500 IU powder and solvent for solution for injection

ADVATE 2000 IU powder and solvent for solution for injection

ADVATE 3000 IU powder and solvent for solution for injection

Octocog alfa (recombinant human coagulation factor VIII)

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 ADVATE is and what it is used for

2.What you need to know before you use ADVATE

3.How to use ADVATE

4.Possible side effects

5.How to store ADVATE

6.Contents of the pack and other information

1. What ADVATE is and what it is used for

ADVATE contains the active substance octocog alfa, human coagulation factor VIII produced by recombinant DNA technology. Factor VIII is necessary for the blood to form clots and stop bleedings. In patients with haemophilia A (inborn lack of factor VIII), it is missing or not working properly.

ADVATE is used for the treatment and prevention of bleeding in patients of all age groups with haemophilia A (an inherited bleeding disorder caused by lack of factor VIII).

ADVATE is prepared without the addition of any human- or animal-derived protein in the entire manufacturing process.

2. What you need to know before you use ADVATE

Do not use ADVATE

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

-if you are allergic to mouse or hamster proteins

If you are unsure about this, ask your doctor.

Warnings and precautions

Talk to your doctor before using ADVATE. You should tell your doctor if you have been previously treated with Factor VIII products, especially if you developed inhibitors, since there might be a higher risk that it happens again. Inhibitors are blocking antibodies against factor VIII that reduce the efficacy

of ADVATE to prevent or control bleeding. Development of inhibitors is a known complication in the treatment of haemophilia A. If your bleeding is not controlled with ADVATE, tell your doctor immediately.

There is a rare risk that you may experience an anaphylactic reaction (a severe, sudden allergic reaction) to ADVATE. You should be aware of the early signs of allergic reactions such as rash, hives, wheals, generalised itching, swelling of lips and tongue, difficulty in breathing, wheezing, tightness in the chest, general feeling of being unwell, and dizziness. These symptoms can constitute an early symptom of an anaphylactic shock, manifestations of which may additionally include extreme dizziness, loss of consciousness, and extreme difficulty in breathing.

If any of these symptoms occur, stop the injection immediately and contact your doctor. Severe symptoms, including difficulty in breathing and (near) fainting, require prompt emergency treatment.

Patients developing Factor VIII inhibitors

If your plasma Factor VIII fails to reach expected levels with ADVATE, or if bleeding is not adequately controlled, it could be due to the development of Factor VIII inhibitors. This will be checked by your doctor. You might need a higher dose of ADVATE or even a different product to control bleedings. Do not increase the total dose of ADVATE to control your bleeding without consulting your doctor.

Children and adolescents

The listed warnings and precautions apply to both adults and children (from 0 to 18 years of age).

Other medicines and ADVATE

Tell your doctor if you are using, have recently used or might use any other medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.

Driving and using machines

ADVATE has no influence on your ability to drive or to use machines.

ADVATE contains sodium

This medicine contains 0.45 mmol sodium (10 mg) per vial. To be taken into consideration by patients on a controlled sodium diet.

3. How to use ADVATE

Treatment with ADVATE will be started by a doctor who is experienced in the care of patients with haemophilia A.

Your doctor will calculate your dose of ADVATE (in international units or IU) depending on your condition and body weight, and on whether it is used for prevention or treatment of bleeding. The frequency of administration will depend on how well ADVATE is working for you. Usually, the replacement therapy with ADVATE is a life-long treatment.

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

Prevention of bleeding

The usual dose of octocog alfa is 20 to 40 IU per kg body weight, administered every 2 to 3 days. However, in some cases, especially in younger patients, more frequent injections or higher doses may be necessary.

Treatment of bleeding

The dose of octocog alfa is calculated depending on your body weight and the factor VIII levels to be achieved. The target factor VIII levels will depend on the severity and location of the bleeding.

Dose (IU) = body weight (kg) x desired Factor VIII rise (% of normal) x 0.5

If you have the impression that the effect of ADVATE is insufficient, talk to your doctor.

Your doctor will perform appropriate laboratory tests to make sure that you have adequate Factor VIII levels. This is particularly important if you are having major surgery.

Use in children and adolescents (from 0 to 18 years of age)

For the treatment of bleeding the dosing in children does not differ from adult patients. For the prevention of bleeding in children under the age of 6, doses of 20 to 50 IU per kg body weight 3 to 4 times weekly are recommended. The administration of ADVATE in children (intravenously) does not differ from the administration in adults. A central venous access device (CVAD) may become necessary to allow frequent infusions of factor VIII products.

How ADVATE is given

ADVATE is usually injected into a vein (intravenously) by your doctor or nurse. You or someone else might also administer ADVATE as an injection, but only after receiving adequate training. Detailed instructions for self-administration are given at the end of this package leaflet.

If you use more ADVATE than you should

Always take ADVATE exactly as your doctor has told you. You should check with your doctor if you are not sure. If you inject more ADVATE than recommended, tell your doctor as soon as possible.

If you forget to use ADVATE

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 ADVATE

Do not stop using ADVATE 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, sudden allergic reactions (anaphylactic) occur, the injection must be stopped immediately. You must contact your doctor immediately if you have any of the following early symptoms of allergic reactions:

-rash, hives, wheals, generalised itching,

-swelling of lips and tongue,

-difficulty in breathing, wheezing, tightness in the chest,

-general feeling of being unwell,

-dizziness and loss of consciousness.

Severe symptoms, including difficulty in breathing and (nearly) fainting, require prompt emergency treatment.

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

Factor VIII inhibitors, headache and fever.

Uncommon side effects (may affect up to 1 in 100 people)

dizziness, flu, fainting, abnormal heartbeat, red itchy bumps on the skin, chest discomfort, injection site bruise, injection site reaction, itching, increased sweating, unusual taste in the mouth, hot flushes, migraines, memory impairment, chills, diarrhoea, nausea, vomiting, shortness of breath, sore throat, infection of the lymphatic vessels, whitening of skin, eye inflammation, rashes, excessive sweating, foot and leg swelling, reduced percentage of red blood cells, increase in a type of white blood cells (monocytes), and pain in the upper abdomen or lower chest.

Related to surgery

catheter-related infection, decreased red cell blood count, swelling of limbs and joints, prolonged bleeding after drain removal, decreased Factor VIII level and post-operative bruise.

Related to central venous access devices (CVAD)

catheter-related infection, systemic infection and local blood clot at the catheter site.

Side effects with unknown frequency (frequency cannot be estimated from the available data) potentially life-threatening reactions (anaphylaxis) and other allergic reactions (hypersensitivity), general disorders (tiredness, lack of energy).

Additional side effects in children

Other than the development of inhibitors in previously untreated paediatric patients (PUPs), and catheter-related complications, no age-specific differences in side effects were noted in the clinical studies.

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 ADVATE

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

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

During the shelf life the blister with the product may be kept at room temperature (up to 25 °C) for a single period not exceeding 6 months. In this case, this medicine expires at the end of this 6 month period or the expiration date printed on the blister, whichever is earlier. Please record the end of the 6 months storage at room temperature on the product carton. The product may not be returned to refrigerated storage after storage at room temperature.

Keep the blister with the product in the outer carton in order to protect from light.

This product is for single use only. Discard any unused solution appropriately.

Use the product immediately once the powder is completely dissolved.

Do not refrigerate the solution after preparation.

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 protect the environment.

6. Contents of the pack and other information

What ADVATE contains

-The active substance is octocog alfa (human coagulation Factor VIII produced by recombinant DNA technology). Each powder vial contains nominally 250, 500, 1000, 1500, 2000, or

3000 IU octocog alfa.

-The other ingredients are mannitol, sodium chloride, histidine, trehalose, calcium chloride, trometamol, polysorbate 80, and glutathione (reduced).

Solvent vial: 5 ml sterilised water for injections

What ADVATE looks like and contents of the pack

ADVATE is a white to off-white friable powder. After reconstitution, the solution is clear, colourless and free from foreign particles.

Marketing Authorisation Holder

Baxter AG

Industriestrasse 67

A-1221 Vienna

Manufacturers

Baxalta Belgium Manufacturing SA

Boulevard René Branquart 80

B-7860 Lessines

Belgium

Baxter SA

Boulevard René Branquart 80

B-7860 Lessines

Belgium

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Baxalta Belgium SPRL

UAB ″Baxter Lithuania″

Tél/Tel: +32 2 892 62 00

Tel: +370 5 269 16 90 / +370 5 252 71 00

България

Luxembourg/Luxemburg

Бакстер България ЕООД

Baxalta Belgium SPRL

тел.: +359 2 9808482

Tél/Tel: +32 2 892 62 00

Česká republika

Magyarország

Baxter Czech spol.s.r.o.

Baxter Hungary Kft.

Tel.: +420 225774111

Tel.: +36 1 202 1980

Danmark

Malta

Baxalta Denmark A/S

Baxalta UK Limited

Tlf: +45 32 70 12 00

Tel.: +44 1 635 798 777

Deutschland

Nederland

Baxalta Deutschland GmbH

Baxalta Netherlands B.V.

Tel: +49 89 262077-011

Tel: +31 30 799 27 77

Eesti

Norge

OÜ Baxter Estonia

Baxalta Norway AS

Tel.: +372 6 515 120

Tlf: +47 22 585 000

Ελλάδα

Österreich

Baxter (Hellas) Ε.Π.Ε.

Baxalta Österreich GmbH

Τηλ.: +30 210 28 80 000

España

Polska

Baxalta Spain S.L.

Baxter Polska Sp. z o.o.

Tel: +34 91 790 42 22

Tel.: +48 22 4883 777

France

Portugal

Baxalta France S.A.S.

Baxalta Portugal, Unipessoal, Lda.

Tél: +33 1 70 96 06 00

Tel: +351 21 122 03 00

Hrvatska

România

Baxter d.o.o.

FARMACEUTICA REMEDIA SA

Tel: +386 1 420 16 80

Tel.: +40 21 321 16 40

Ireland

Slovenija

Baxalta UK Limited

Baxter d.o.o.

Tel: +44 1 635 798 777

Tel.: +386 1 420 16 80

Ísland

Slovenská republika

Lyfjaver ehf.

Baxter Slovakia s.r.o.

Sími: +354 533 6100

Tel: +421 2 3210 1150

Italia

Suomi/Finland

Baxalta Italy S.r.l.

Baxalta Finland Oy

Tel: +39 06 45224 600

Puh/Tel: +358 201478200

Κύπρος

Sverige

Baxter (Hellas) Ε.Π.Ε.

Baxalta Sweden AB

Τηλ.: +30 210 28 80 000

Tel: +46 8 50 53 26 00

Latvija

United Kingdom

SIA BAXTER Latvia

Baxalta UK Limited

Tel.: +371 67 784 784

Tel: +44 1 635 798 777

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

Instructions for preparation and administration

ADVATE must not be mixed with other medicinal products or solvents.

It is strongly recommended that every time ADVATE is administered, the name and batch number of the product are recorded.

Instructions for reconstitution

Do not use after the expiry date stated on the labels and carton.

Do not use if the lid is not completely sealed on the blister

Do not refrigerate the solution after preparation.

1.If the product is still stored in a refrigerator, take the sealed blister (contains powder and solvent vials preassembled with the system for reconstitution) from the refrigerator and let it reach room temperature (between 15 °C and 25 °C).

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

3.Open the ADVATE package by peeling away the lid. Remove the BAXJECT III system from the blister.

4.Place the ADVATE on a flat surface with the solvent vial on top (Fig. 1). The solvent vial has a blue stripe. Do not remove the blue cap until instructed in a later step.

5.With one hand holding the ADVATE in the BAXJECT III system, press down firmly on the solvent vial with the other hand until the system is fully collapsed and the solvent flows down into the ADVATE vial (Fig. 2). Do not tilt the system until the transfer is complete.

6.Verify that the solvent transfer is complete. Swirl gently until all material is dissolved. Be sure that the ADVATE powder is completely dissolved, otherwise not all reconstituted solution will pass through the device filter. The product dissolves rapidly (usually in less than 1 minute).

After reconstitution the solution should be clear, colourless and free from foreign particles.

Fig. 1

Fig. 2

Fig. 3

Instructions for injection

Aseptic technique is required during administration.

For administration the use of a luer-lock syringe is required.

Important note:

Do not try to administer the injection unless you have received special training from your doctor or nurse.

Inspect the prepared solution for particulate matter and discoloration prior to administration (the solution should be clear, colourless and free from foreign particles).

Do not use ADVATE if the solution is not fully clear or not completely dissolved.

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

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.

3.Disconnect the syringe.

4.Attach a butterfly needle to the syringe and inject the reconstituted solution into a vein. The solution should be administered slowly, at a rate as determined by the patient’s comfort level, not to exceed 10 ml per minute. (See Section 4 “Possible side effects”).

5.Discard any unused solution appropriately.

-------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

On demand treatment

In case of the following haemorrhagic events, the factor VIII 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.

The dose and frequency of administration should be adapted to the clinical response in the individual case. Under certain circumstances (e.g. presence of a low-titre inhibitor), doses larger than those calculated using the formula may be necessary.

Degree of haemorrhage/type of

Factor VIII level

Frequency of doses (hours)/duration

surgical procedure

required (% or IU/dl)

of therapy (days)

Haemorrhage

 

 

Early haemarthrosis, muscle

20 – 40

Repeat injections every 12 to 24 hours

bleeding or oral bleeding.

 

(8 to 24 hours for patients under the age

 

 

of 6) for at least 1 day, until the

 

 

bleeding episode, as indicated by pain,

 

 

is resolved or healing is achieved.

More extensive haemarthrosis,

30 – 60

Repeat injections every 12 to 24 hours

muscle bleeding or haematoma.

 

(8 to 24 hours for patients under the age

 

 

of 6) for 3 – 4 days or more until pain

 

 

and acute disability are resolved.

Life-threatening haemorrhages.

60 – 100

Repeat injections every 8 to 24 hours

 

 

(6 to 12 hours for patients under the age

 

 

of 6) until threat is resolved.

Surgery

 

 

Minor

30 – 60

Every 24 hours (12 to 24 hours for

Including tooth extraction.

 

patients under the age of 6), at

 

 

least 1 day, until healing is achieved.

Major

80 – 100

Repeat injections every 8 to 24 hours

 

(pre- and postoperative)

(6 to 24 hours for patients under the age

 

 

of 6) until adequate wound healing,

 

 

then continue therapy for at least

 

 

another 7 days to maintain a factor VIII

 

 

activity of 30% to 60% (IU/dl).

Package leaflet: Information for the user

ADVATE 250 IU powder and solvent for solution for injection

ADVATE 500 IU powder and solvent for solution for injection

ADVATE 1000 IU powder and solvent for solution for injection

ADVATE 1500 IU powder and solvent for solution for injection

Octocog alfa (recombinant human coagulation factor VIII)

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 ADVATE is and what it is used for

2.What you need to know before you use ADVATE

3.How to use ADVATE

4.Possible side effects

5.How to store ADVATE

6.Contents of the pack and other information

1. What ADVATE is and what it is used for

ADVATE contains the active substance octocog alfa, human coagulation factor VIII produced by recombinant DNA technology. Factor VIII is necessary for the blood to form clots and stop bleedings. In patients with haemophilia A (inborn lack of factor VIII), it is missing or not working properly.

ADVATE is used for the treatment and prevention of bleeding in patients of all age groups with haemophilia A (an inherited bleeding disorder caused by lack of factor VIII).

ADVATE is prepared without the addition of any human- or animal-derived protein in the entire manufacturing process.

2. What you need to know before you use ADVATE

Do not use ADVATE

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

-if you are allergic to mouse or hamster proteins

If you are unsure about this, ask your doctor.

Warnings and precautions

Talk to your doctor before using ADVATE. You should tell your doctor if you have been previously treated with Factor VIII products, especially if you developed inhibitors, since there might be a higher risk that it happens again. Inhibitors are blocking antibodies against factor VIII that reduce the efficacy of ADVATE to prevent or control bleeding. Development of inhibitors is a known complication in the

treatment of haemophilia A. If your bleeding is not controlled with ADVATE, tell your doctor immediately.

There is a rare risk that you may experience an anaphylactic reaction (a severe, sudden allergic reaction) to ADVATE. You should be aware of the early signs of allergic reactions such as rash, hives, wheals, generalised itching, swelling of lips and tongue, difficulty in breathing, wheezing, tightness in the chest, general feeling of being unwell, and dizziness. These symptoms can constitute an early symptom of an anaphylactic shock, manifestations of which may additionally include extreme dizziness, loss of consciousness, and extreme difficulty in breathing.

If any of these symptoms occur, stop the injection immediately and contact your doctor. Severe symptoms, including difficulty in breathing and (near) fainting, require prompt emergency treatment.

Patients developing Factor VIII inhibitors

If your plasma Factor VIII fails to reach expected levels with ADVATE, or if bleeding is not adequately controlled, it could be due to the development of Factor VIII inhibitors. This will be checked by your doctor. You might need a higher dose of ADVATE or even a different product to control bleedings. Do not increase the total dose of ADVATE to control your bleeding without consulting your doctor.

Children and adolescents

The listed warnings and precautions apply to both adults and children (from 0 to 18 years of age).

Other medicines and ADVATE

Tell your doctor if you are using, have recently used or might use any other medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.

Driving and using machines

ADVATE has no influence on your ability to drive or to use machines.

ADVATE contains sodium

This medicine contains 0.45 mmol sodium (10 mg) per vial. To be taken into consideration by patients on a controlled sodium diet.

Misapplication of ADVATE

Misapplication (injection into the artery or outside the vein) should be avoided as mild, short term injection site reactions, such as bruising and redness, may occur.

3. How to use ADVATE

Treatment with ADVATE will be started by a doctor who is experienced in the care of patients with haemophilia A.

Your doctor will calculate your dose of ADVATE (in international units or IU) depending on your condition and body weight, and on whether it is used for prevention or treatment of bleeding. The frequency of administration will depend on how well ADVATE is working for you. Usually, the replacement therapy with ADVATE is a life-long treatment.

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

Prevention of bleeding

The usual dose of octocog alfa is 20 to 40 IU per kg body weight, administered every 2 to 3 days. However, in some cases, especially in younger patients, more frequent injections or higher doses may be necessary.

Treatment of bleeding

The dose of octocog alfa is calculated depending on your body weight and the factor VIII levels to be achieved. The target factor VIII levels will depend on the severity and location of the bleeding.

Dose (IU) = body weight (kg) x desired Factor VIII rise (% of normal) x 0.5

If you have the impression that the effect of ADVATE is insufficient, talk to your doctor.

Your doctor will perform appropriate laboratory tests to make sure that you have adequate Factor VIII levels. This is particularly important if you are having major surgery.

Use in children and adolescents (from 0 to 18 years of age)

For the treatment of bleeding the dosing in children does not differ from adult patients. For the prevention of bleeding in children under the age of 6, doses of 20 to 50 IU per kg body weight 3 to 4 times weekly are recommended. The administration of ADVATE in children (intravenously) does not differ from the administration in adults. A central venous access device (CVAD) may become necessary to allow frequent infusions of factor VIII products. This presentation is available with 5 ml solvent and 2 ml solvent. However, for the 2 ml presentation there is no documentation available in children below 2 years of age.

Due to the decrease in injection volume for ADVATE reconstituted in 2 ml, the time to react to hypersensitivity reactions during an injection is further reduced. Therefore, caution is advised during injection of ADVATE reconstituted in 2 ml, especially in children.

How ADVATE is given

ADVATE is usually injected into a vein (intravenously) by your doctor or nurse. You or someone else might also administer ADVATE as an injection, but only after receiving adequate training. Detailed instructions for self-administration are given at the end of this package leaflet.

If you use more ADVATE than you should

Always take ADVATE exactly as your doctor has told you. You should check with your doctor if you are not sure. If you inject more ADVATE than recommended, tell your doctor as soon as possible.

If you forget to use ADVATE

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 ADVATE

Do not stop using ADVATE 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, sudden allergic reactions (anaphylactic) occur, the injection must be stopped immediately. You must contact your doctor immediately if you have any of the following early symptoms of allergic reactions:

-rash, hives, wheals, generalised itching,

-swelling of lips and tongue,

-difficulty in breathing, wheezing, tightness in the chest,

-general feeling of being unwell,

-dizziness and loss of consciousness.

Severe symptoms, including difficulty in breathing and (nearly) fainting, require prompt emergency treatment.

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

Factor VIII inhibitors, headache and fever.

Uncommon side effects (may affect up to 1 in 100 people)

dizziness, flu, fainting, abnormal heartbeat, red itchy bumps on the skin, chest discomfort, injection site bruise, injection site reaction, itching, increased sweating, unusual taste in the mouth, hot flushes, migraines, memory impairment, chills, diarrhoea, nausea, vomiting, shortness of breath, sore throat, infection of the lymphatic vessels, whitening of skin, eye inflammation, rashes, excessive sweating, foot and leg swelling, reduced percentage of red blood cells, increase in a type of white blood cells (monocytes), and pain in the upper abdomen or lower chest.

Related to surgery

catheter-related infection, decreased red cell blood count, swelling of limbs and joints, prolonged bleeding after drain removal, decreased Factor VIII level and post-operative bruise.

Related to central venous access devices (CVAD)

catheter-related infection, systemic infection and local blood clot at the catheter site.

Side effects with unknown frequency (frequency cannot be estimated from the available data) potentially life-threatening reactions (anaphylaxis) and other allergic reactions (hypersensitivity), general disorders (tiredness, lack of energy).

Additional side effects in children

Other than the development of inhibitors in previously untreated paediatric patients (PUPs), and catheter-related complications, no age-specific differences in side effects were noted in the clinical studies.

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 ADVATE

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

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

During the shelf life the powder vial may be kept at room temperature (up to 25 °C) for a single period not exceeding 6 months. In this case, this medicine expires at the end of this 6 month period or the expiration date printed on the product vial, whichever is earlier. Please record the end of the 6 months storage at room temperature on the product carton. The product may not be returned to refrigerated storage after storage at room temperature.

Keep the vial in the outer carton in order to protect from light.

This product is for single use only. Discard any unused solution appropriately.

Use the product immediately once the powder is completely dissolved.

Do not refrigerate the solution after preparation.

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 protect the environment.

6. Contents of the pack and other information

What ADVATE contains

-The active substance is octocog alfa (human coagulation Factor VIII produced by recombinant DNA technology). Each powder vial contains nominally 250, 500, 1000, or 1500 IU octocog alfa.

-The other ingredients are mannitol, sodium chloride, histidine, trehalose, calcium chloride, trometamol, polysorbate 80, and glutathione (reduced).

Solvent vial: 2 ml sterilised water for injections

What ADVATE looks like and contents of the pack

ADVATE is a white to off-white friable powder. After reconstitution, the solution is clear, colourless and free from foreign particles.

Each pack also contains a device for reconstitution (BAXJECT II).

Marketing Authorisation Holder

Baxter AG

Industriestrasse 67

A-1221 Vienna

Manufacturers

Baxalta Belgium Manufacturing SA

Boulevard René Branquart 80

B-7860 Lessines

Belgium

Baxter SA

Boulevard René Branquart 80

B-7860 Lessines

Belgium

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Baxalta Belgium SPRL

UAB ″Baxter Lithuania″

Tél/Tel: +32 2 892 62 00

Tel: +370 5 269 16 90 / +370 5 252 71 00

България

Luxembourg/Luxemburg

Бакстер България ЕООД

Baxalta Belgium SPRL

тел.: +359 2 9808482

Tél/Tel: +32 2 892 62 00

Česká republika

Magyarország

Baxter Czech spol.s.r.o.

Baxter Hungary Kft.

Tel.: +420 225774111

Tel.: +36 1 202 1980

Danmark

Malta

Baxalta Denmark A/S

Baxalta UK Limited

Tlf: +45 32 70 12 00

Tel.: +44 1 635 798 777

Deutschland

Nederland

Baxalta Deutschland GmbH

Baxalta Netherlands B.V.

Tel: +49 89 262077-011

Tel: +31 30 799 27 77

Eesti

Norge

OÜ Baxter Estonia

Baxalta Norway AS

Tel.: +372 6 515 120

Tlf: +47 22 585 000

Ελλάδα

Österreich

Baxter (Hellas) Ε.Π.Ε.

Baxalta Österreich GmbH

Τηλ.: +30 210 28 80 000

España

Polska

Baxalta Spain S.L.

Baxter Polska Sp. z o.o.

Tel: +34 91 790 42 22

Tel.: +48 22 4883 777

France

Portugal

Baxalta France S.A.S.

Baxalta Portugal, Unipessoal, Lda.

Tél: +33 1 70 96 06 00

Tel: +351 21 122 03 00

Hrvatska

România

Baxter d.o.o.

FARMACEUTICA REMEDIA SA

Tel: +386 1 420 16 80

Tel.: +40 21 321 16 40

Ireland

Slovenija

Baxalta UK Limited

Baxter d.o.o.

Tel: +44 1 635 798 777

Tel.: +386 1 420 16 80

Ísland

Slovenská republika

Lyfjaver ehf.

Baxter Slovakia s.r.o.

Sími: +354 533 6100

Tel: +421 2 3210 1150

Italia

Suomi/Finland

Baxalta Italy S.r.l.

Baxalta Finland Oy

Tel: +39 06 45224 600

Puh/Tel: +358 201478200

Κύπρος

Sverige

Baxter (Hellas) Ε.Π.Ε.

Baxalta Sweden AB

Τηλ.: +30 210 28 80 000

Tel: +46 8 50 53 26 00

Latvija

United Kingdom

SIA BAXTER Latvia

Baxalta UK Limited

Tel.: +371 67 784 784

Tel: +44 1 635 798 777

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

-------------------------------------------------------------------------------------------------------------------------

Instructions for preparation and administration

Aseptic technique is required during preparation of the solution and administration.

Use only the sterilised water for injections and the reconstitution device for preparation of the solution that are provided with each package of ADVATE. ADVATE must not be mixed with other medicinal products or solvents.

It is strongly recommended that every time ADVATE is administered, the name and batch number of the product are recorded.

Instructions for reconstitution

Do not use after the expiry date stated on the labels and carton.

Do not use if the BAXJECT II device, its sterile barrier system or its packaging is damaged or shows any sign of deterioration as indicated by the symbol: .

Do not refrigerate the solution after preparation.

1.If the product is still stored in a refrigerator, take both the ADVATE powder and solvent vials from the refrigerator and let them reach room temperature (between 15 °C and 25 °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. Do not use if the BAXJECT II device, its sterile barrier system or its packaging is damaged or shows any sign of deterioration.

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.For reconstitution only the sterilised water for injections and the reconstitution device provided in the pack should be used. 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 ADVATE powder stopper. The vacuum will draw the solvent into the ADVATE powder vial (Fig. c).

8.Swirl gently until all material is dissolved. Be sure that the ADVATE powder is completely dissolved, otherwise not all reconstituted solution will pass through the device filter. The product dissolves rapidly (usually in less than 1 minute). After reconstitution the solution should be clear, colourless and free from foreign particles.

Fig. a

Fig. b

Fig. c

Instructions for injection

For administration the use of a luer-lock syringe is required.

Important note:

Do not try to administer the injection unless you have received special training from your doctor or nurse.

Inspect the prepared solution for particulate matter and discoloration prior to administration (the solution should be clear, colourless and free from foreign particles).

Do not use ADVATE if the solution is not fully clear or not completely dissolved.

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 and inject the reconstituted solution into a vein. The solution should be administered slowly, at a rate as determined by the patient’s comfort level, not to exceed 10 ml per minute. (See Section 4 “Possible side effects”).

5.Discard any unused solution appropriately.

Fig. d

Fig. e

-------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

On demand treatment

In case of the following haemorrhagic events, the factor VIII 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.

The dose and frequency of administration should be adapted to the clinical response in the individual case. Under certain circumstances (e.g. presence of a low-titre inhibitor), doses larger than those calculated using the formula may be necessary.

Degree of haemorrhage/type

Factor VIII level

Frequency of doses (hours)/duration of

of surgical procedure

required (% or IU/dl)

therapy (days)

Haemorrhage

 

 

Early haemarthrosis, muscle

20 – 40

Repeat injections every 12 to 24 hours

bleeding or oral bleeding.

 

(8 to 24 hours for patients under the age

 

 

of 6) for at least 1 day, until the bleeding

 

 

episode, as indicated by pain, is resolved

 

 

or healing is achieved.

More extensive haemarthrosis,

30 – 60

Repeat injections every 12 to 24 hours

muscle bleeding or haematoma.

 

(8 to 24 hours for patients under the age

 

 

of 6) for 3 – 4 days or more until pain and

 

 

acute disability are resolved.

Life-threatening haemorrhages.

60 – 100

Repeat injections every 8 to 24 hours

 

 

(6 to 12 hours for patients under the age

 

 

of 6) until threat is resolved.

Surgery

 

 

Minor

30 – 60

Every 24 hours (12 to 24 hours for

Including tooth extraction.

 

patients under the age of 6), at

 

 

least 1 day, until healing is achieved.

Major

80 – 100

Repeat injections every 8 to 24 hours

 

(pre- and

(6 to 24 hours for patients under the age

 

postoperative)

of 6) until adequate wound healing, then

 

 

continue therapy for at least

 

 

another 7 days to maintain a factor VIII

 

 

activity of 30% to 60% (IU/dl).

Package leaflet: Information for the user

ADVATE 250 IU powder and solvent for solution for injection

ADVATE 500 IU powder and solvent for solution for injection

ADVATE 1000 IU powder and solvent for solution for injection

ADVATE 1500 IU powder and solvent for solution for injection

Octocog alfa (recombinant human coagulation factor VIII)

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 ADVATE is and what it is used for

2.What you need to know before you use ADVATE

3.How to use ADVATE

4.Possible side effects

5.How to store ADVATE

6.Contents of the pack and other information

1. What ADVATE is and what it is used for

ADVATE contains the active substance octocog alfa, human coagulation factor VIII produced by recombinant DNA technology. Factor VIII is necessary for the blood to form clots and stop bleedings. In patients with haemophilia A (inborn lack of factor VIII), it is missing or not working properly.

ADVATE is used for the treatment and prevention of bleeding in patients of all age groups with haemophilia A (an inherited bleeding disorder caused by lack of factor VIII).

ADVATE is prepared without the addition of any human- or animal-derived protein in the entire manufacturing process.

2. What you need to know before you use ADVATE

Do not use ADVATE

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

-if you are allergic to mouse or hamster proteins

If you are unsure about this, ask your doctor.

Warnings and precautions

Talk to your doctor before using ADVATE. You should tell your doctor if you have been previously treated with Factor VIII products, especially if you developed inhibitors, since there might be a higher risk that it happens again. Inhibitors are blocking antibodies against factor VIII that reduce the efficacy of ADVATE to prevent or control bleeding. Development of inhibitors is a known complication in the

treatment of haemophilia A. If your bleeding is not controlled with ADVATE, tell your doctor immediately.

There is a rare risk that you may experience an anaphylactic reaction (a severe, sudden allergic reaction) to ADVATE. You should be aware of the early signs of allergic reactions such as rash, hives, wheals, generalised itching, swelling of lips and tongue, difficulty in breathing, wheezing, tightness in the chest, general feeling of being unwell, and dizziness. These symptoms can constitute an early symptom of an anaphylactic shock, manifestations of which may additionally include extreme dizziness, loss of consciousness, and extreme difficulty in breathing.

If any of these symptoms occur, stop the injection immediately and contact your doctor. Severe symptoms, including difficulty in breathing and (near) fainting, require prompt emergency treatment.

Patients developing Factor VIII inhibitors

If your plasma Factor VIII fails to reach expected levels with ADVATE, or if bleeding is not adequately controlled, it could be due to the development of Factor VIII inhibitors. This will be checked by your doctor. You might need a higher dose of ADVATE or even a different product to control bleedings. Do not increase the total dose of ADVATE to control your bleeding without consulting your doctor.

Children and adolescents

The listed warnings and precautions apply to both adults and children (from 0 to 18 years of age).

Other medicines and ADVATE

Tell your doctor if you are using, have recently used or might use any other medicines.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.

Driving and using machines

ADVATE has no influence on your ability to drive or to use machines.

ADVATE contains sodium

This medicine contains 0.45 mmol sodium (10 mg) per vial. To be taken into consideration by patients on a controlled sodium diet.

Misapplication of ADVATE

Misapplication (injection into the artery or outside the vein) should be avoided as mild, short term injection site reactions, such as bruising and redness, may occur.

3. How to use ADVATE

Treatment with ADVATE will be started by a doctor who is experienced in the care of patients with haemophilia A.

Your doctor will calculate your dose of ADVATE (in international units or IU) depending on your condition and body weight, and on whether it is used for prevention or treatment of bleeding. The frequency of administration will depend on how well ADVATE is working for you. Usually, the replacement therapy with ADVATE is a life-long treatment.

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

Prevention of bleeding

The usual dose of octocog alfa is 20 to 40 IU per kg body weight, administered every 2 to 3 days. However, in some cases, especially in younger patients, more frequent injections or higher doses may be necessary.

Treatment of bleeding

The dose of octocog alfa is calculated depending on your body weight and the factor VIII levels to be achieved. The target factor VIII levels will depend on the severity and location of the bleeding.

Dose (IU) = body weight (kg) x desired Factor VIII rise (% of normal) x 0.5

If you have the impression that the effect of ADVATE is insufficient, talk to your doctor.

Your doctor will perform appropriate laboratory tests to make sure that you have adequate Factor VIII levels. This is particularly important if you are having major surgery.

Use in children and adolescents (from 0 to 18 years of age)

For the treatment of bleeding the dosing in children does not differ from adult patients. For the prevention of bleeding in children under the age of 6, doses of 20 to 50 IU per kg body weight 3 to 4 times weekly are recommended. The administration of ADVATE in children (intravenously) does not differ from the administration in adults. A central venous access device (CVAD) may become necessary to allow frequent infusions of factor VIII products. This presentation is available with 5 ml solvent and 2 ml solvent. However, for the 2 ml presentation there is no documentation available in children below 2 years of age.

Due to the decrease in injection volume for ADVATE reconstituted in 2 ml, the time to react to hypersensitivity reactions during an injection is further reduced. Therefore, caution is advised during injection of ADVATE reconstituted in 2 ml, especially in children.

How ADVATE is given

ADVATE is usually injected into a vein (intravenously) by your doctor or nurse. You or someone else might also administer ADVATE as an injection, but only after receiving adequate training. Detailed instructions for self-administration are given at the end of this package leaflet.

If you use more ADVATE than you should

Always take ADVATE exactly as your doctor has told you. You should check with your doctor if you are not sure. If you inject more ADVATE than recommended, tell your doctor as soon as possible.

If you forget to use ADVATE

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 ADVATE

Do not stop using ADVATE 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, sudden allergic reactions (anaphylactic) occur, the injection must be stopped immediately. You must contact your doctor immediately if you have any of the following early symptoms of allergic reactions:

-rash, hives, wheals, generalised itching,

-swelling of lips and tongue,

-difficulty in breathing, wheezing, tightness in the chest,

-general feeling of being unwell,

-dizziness and loss of consciousness.

Severe symptoms, including difficulty in breathing and (nearly) fainting, require prompt emergency treatment.

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

Factor VIII inhibitors, headache and fever.

Uncommon side effects (may affect up to 1 in 100 people)

dizziness, flu, fainting, abnormal heartbeat, red itchy bumps on the skin, chest discomfort, injection site bruise, injection site reaction, itching, increased sweating, unusual taste in the mouth, hot flushes, migraines, memory impairment, chills, diarrhoea, nausea, vomiting, shortness of breath, sore throat, infection of the lymphatic vessels, whitening of skin, eye inflammation, rashes, excessive sweating, foot and leg swelling, reduced percentage of red blood cells, increase in a type of white blood cells (monocytes), and pain in the upper abdomen or lower chest.

Related to surgery

catheter-related infection, decreased red cell blood count, swelling of limbs and joints, prolonged bleeding after drain removal, decreased Factor VIII level and post-operative bruise.

Related to central venous access devices (CVAD)

catheter-related infection, systemic infection and local blood clot at the catheter site.

Side effects with unknown frequency (frequency cannot be estimated from the available data) potentially life-threatening reactions (anaphylaxis) and other allergic reactions (hypersensitivity), general disorders (tiredness, lack of energy).

Additional side effects in children

Other than the development of inhibitors in previously untreated paediatric patients (PUPs), and catheter-related complications, no age-specific differences in side effects were noted in the clinical studies.

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 ADVATE

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

Store in a refrigerator (2 °C – 8 °C).

Do not freeze.

During the shelf life the blister with the product may be kept at room temperature (up to 25 °C) for a single period not exceeding 6 months. In this case, this medicine expires at the end of this 6 month period or the expiration date printed on the blister, whichever is earlier. Please record the end of the 6 months storage at room temperature on the product carton. The product may not be returned to refrigerated storage after storage at room temperature.

Keep the blister with the product in the outer carton in order to protect from light.

This product is for single use only. Discard any unused solution appropriately.

Use the product immediately once the powder is completely dissolved.

Do not refrigerate the solution after preparation.

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 protect the environment.

6. Contents of the pack and other information

What ADVATE contains

-The active substance is octocog alfa (human coagulation Factor VIII produced by recombinant DNA technology). Each powder vial contains nominally 250, 500, 1000, or 1500 IU octocog alfa.

-The other ingredients are mannitol, sodium chloride, histidine, trehalose, calcium chloride, trometamol, polysorbate 80, and glutathione (reduced).

Solvent vial: 2 ml sterilised water for injections

What ADVATE looks like and contents of the pack

ADVATE is a white to off-white friable powder. After reconstitution, the solution is clear, colourless and free from foreign particles.

Marketing Authorisation Holder

Baxter AG

Industriestrasse 67

A-1221 Vienna

Manufacturers

Baxalta Belgium Manufacturing SA

Boulevard René Branquart 80

B-7860 Lessines

Belgium

Baxter SA

Boulevard René Branquart 80

B-7860 Lessines

Belgium

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien

Lietuva

Baxalta Belgium SPRL

UAB ″Baxter Lithuania″

Tél/Tel: +32 2 892 62 00

Tel: +370 5 269 16 90 / +370 5 252 71 00

България

Luxembourg/Luxemburg

Бакстер България ЕООД

Baxalta Belgium SPRL

тел.: +359 2 9808482

Tél/Tel: +32 2 892 62 00

Česká republika

Magyarország

Baxter Czech spol.s.r.o.

Baxter Hungary Kft.

Tel.: +420 225774111

Tel.: +36 1 202 1980

Danmark

Malta

Baxalta Denmark A/S

Baxalta UK Limited

Tlf: +45 32 70 12 00

Tel.: +44 1 635 798 777

Deutschland

Nederland

Baxalta Deutschland GmbH

Baxalta Netherlands B.V.

Tel: +49 89 262077-011

Tel: +31 30 799 27 77

Eesti

Norge

OÜ Baxter Estonia

Baxalta Norway AS

Tel.: +372 6 515 120

Tlf: +47 22 585 000

Ελλάδα

Österreich

Baxter (Hellas) Ε.Π.Ε.

Baxalta Österreich GmbH

Τηλ.: +30 210 28 80 000

España

Polska

Baxalta Spain S.L.

Baxter Polska Sp. z o.o.

Tel: +34 91 790 42 22

Tel.: +48 22 4883 777

France

Portugal

Baxalta France S.A.S.

Baxalta Portugal, Unipessoal, Lda.

Tél: +33 1 70 96 06 00

Tel: +351 21 122 03 00

Hrvatska

România

Baxter d.o.o.

FARMACEUTICA REMEDIA SA

Tel: +386 1 420 16 80

Tel.: +40 21 321 16 40

Ireland

Slovenija

Baxalta UK Limited

Baxter d.o.o.

Tel: +44 1 635 798 777

Tel.: +386 1 420 16 80

Ísland

Slovenská republika

Lyfjaver ehf.

Baxter Slovakia s.r.o.

Sími: +354 533 6100

Tel: +421 2 3210 1150

Italia

Suomi/Finland

Baxalta Italy S.r.l.

Baxalta Finland Oy

Tel: +39 06 45224 600

Puh/Tel: +358 201478200

Κύπρος

Sverige

Baxter (Hellas) Ε.Π.Ε.

Baxalta Sweden AB

Τηλ.: +30 210 28 80 000

Tel: +46 8 50 53 26 00

Latvija

United Kingdom

SIA BAXTER Latvia

Baxalta UK Limited

Tel.: +371 67 784 784

Tel: +44 1 635 798 777

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/

-------------------------------------------------------------------------------------------------------------------------

Instructions for preparation and administration

ADVATE must not be mixed with other medicinal products or solvents.

It is strongly recommended that every time ADVATE is administered, the name and batch number of the product are recorded.

Instructions for reconstitution

Do not use after the expiry date stated on the labels and carton.

Do not use if the lid is not completely sealed on the blister

Do not refrigerate the solution after preparation.

1.If the product is still stored in a refrigerator, take the sealed blister (contains powder and solvent vials preassembled with the system for reconstitution) from the refrigerator and let it reach room temperature (between 15 °C and 25 °C).

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

3.Open the ADVATE package by peeling away the lid. Remove the BAXJECT III system from the blister.

4.Place the ADVATE on a flat surface with the solvent vial on top (Fig. 1). The solvent vial has a blue stripe. Do not remove the blue cap until instructed in a later step.

5.With one hand holding the ADVATE in the BAXJECT III system, press down firmly on the solvent vial with the other hand until the system is fully collapsed and the solvent flows down into the ADVATE vial (Fig. 2). Do not tilt the system until the transfer is complete.

6.Verify that the solvent transfer is complete. Swirl gently until all material is dissolved. Be sure that the ADVATE powder is completely dissolved, otherwise not all reconstituted solution will pass through the device filter. The product dissolves rapidly (usually in less than 1 minute).

After reconstitution the solution should be clear, colourless and free from foreign particles.

Fig. 1

Fig. 2

Fig. 3

Instructions for injection

Aseptic technique is required during administration.

For administration the use of a luer-lock syringe is required.

Important note:

Do not try to administer the injection unless you have received special training from your doctor or nurse.

Inspect the prepared solution for particulate matter and discoloration prior to administration (the solution should be clear, colourless and free from foreign particles).

Do not use ADVATE if the solution is not fully clear or not completely dissolved.

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

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.

3.Disconnect the syringe.

4.Attach a butterfly needle to the syringe and inject the reconstituted solution into a vein. The solution should be administered slowly, at a rate as determined by the patient’s comfort level, not to exceed 10 ml per minute. (See Section 4 “Possible side effects”).

5.Discard any unused solution appropriately.

-------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

On demand treatment

In case of the following haemorrhagic events, the factor VIII 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.

The dose and frequency of administration should be adapted to the clinical response in the individual case. Under certain circumstances (e.g. presence of a low-titre inhibitor), doses larger than those calculated using the formula may be necessary.

Degree of haemorrhage/type

Factor VIII level

Frequency of doses (hours)/duration of

of surgical procedure

required (% or IU/dl)

therapy (days)

Haemorrhage

 

 

Early haemarthrosis, muscle

20 – 40

Repeat injections every 12 to 24 hours

bleeding or oral bleeding.

 

(8 to 24 hours for patients under the age

 

 

of 6) for at least 1 day, until the bleeding

 

 

episode, as indicated by pain, is resolved

 

 

or healing is achieved.

More extensive haemarthrosis,

30 – 60

Repeat injections every 12 to 24 hours

muscle bleeding or haematoma.

 

(8 to 24 hours for patients under the age

 

 

of 6) for 3 – 4 days or more until pain and

 

 

acute disability are resolved.

Life-threatening haemorrhages.

60 – 100

Repeat injections every 8 to 24 hours

 

 

(6 to 12 hours for patients under the age

 

 

of 6) until threat is resolved.

Surgery

 

 

Minor

30 – 60

Every 24 hours (12 to 24 hours for

Including tooth extraction.

 

patients under the age of 6), at

 

 

least 1 day, until healing is achieved.

Major

80 – 100

Repeat injections every 8 to 24 hours

 

(pre- and

(6 to 24 hours for patients under the age

 

postoperative)

of 6) until adequate wound healing, then

 

 

continue therapy for at least

 

 

another 7 days to maintain a factor VIII

 

 

activity of 30% to 60% (IU/dl).

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