ADYNOVI 250 IU Powder and solvent for injectable solution

Зміст інструкції

1. ADYNOVI 250 IU / 5 mL powder and solvent for injectable solution, 500 IU / 5 mL powder and solvent for injectable solution, 1 000 IU / 5 mL powder and solvent for injectable solution, 2 000 IU / 5 mL powder and solvent for injectable solution, 3 000 IU / 5 mL powder and solvent for injectable solution
   1. What is ADYNOVI and what is it used for
   2. What you need to know before using ADYNOVI
   3. How to use ADYNOVI
   4. Possible side effects
   5. How to store ADYNOVI
   6. Content of the pack and other information
2. ADYNOVI 250 IU / 5 mL powder and solvent for injectable solution, 500 IU / 5 mL powder and solvent for injectable solution, 1 000 IU / 5 mL powder and solvent for injectable solution, 2 000 IU / 5 mL powder and solvent for injectable solution, 3 000 IU / 5 mL powder and solvent for injectable solution
   1. What is ADYNOVI and what is it used for
   2. What you need to know before you use ADYNOVI
   3. How to use ADYNOVI
   4. Possible side effects
   5. How to store ADYNOVI
   6. Contents of the pack and other information
3. ADYNOVI 250 IU / 2 mL powder and solvent for injectable solution, 500 IU / 2 mL powder and solvent for injectable solution, 1,000 IU / 2 mL powder and solvent for injectable solution
   1. What is ADYNOVI and what is it used for
   2. What you need to know before using ADYNOVI
   3. How to use ADYNOVI
   4. Possible side effects
   5. How to store ADYNOVI
   6. Content of the pack and other information
4. ADYNOVI 250 IU / 2 mL powder and solvent for injectable solution, 500 IU / 2 mL powder and solvent for injectable solution, 1 000 IU / 2 mL powder and solvent for injectable solution
   1. What is ADYNOVI and what is it used for
   2. What you need to know before using ADYNOVI
   3. How to use ADYNOVI
   4. Possible side effects
   5. How to store ADYNOVI
   6. Contents of the pack and other information

ADYNOVI 250 IU / 5 mL powder and solvent for injectable solution, 500 IU / 5 mL powder and solvent for injectable solution, 1 000 IU / 5 mL powder and solvent for injectable solution, 2 000 IU / 5 mL powder and solvent for injectable solution, 3 000 IU / 5 mL powder and solvent for injectable solution

rurioctocog alfa pegol (recombinant human coagulation factor VIII pegylated)
Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicinal product. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before you use this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, ask your doctor. See section 4.

Contents of this leaflet:

• 1. What ADYNOVI is and what it is used for
• 2. What you need to know before you use ADYNOVI
• 3. How to use ADYNOVI
• 4. Possible side effects
• 5. How to store ADYNOVI
• 6. Contents of the pack and other information

1. What is ADYNOVI and what is it used for

ADYNOVI contains the active substance rurioctocog alfa pegol, human coagulation factor VIII
pegylated. Human coagulation factor VIII has been modified to prolong its duration
of action. Factor VIII is necessary for blood to clot and stop bleeding. In patients
with hemophilia A (congenital deficiency of factor VIII) it is absent or does not act
correctly.
ADYNOVI is used for the treatment and prevention of bleeding in patients aged 12
years and older with hemophilia A (an inherited bleeding disorder caused by a deficiency of
factor VIII).

2. What you need to know before using ADYNOVI

Do not use ADYNOVI:

• if you are allergic to rurioctocog alfa pegol, to octocog alfa or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to mouse or hamster proteins

If you have any doubts, ask your doctor.

Warnings and precautions
It is important to keep track of the lot number of ADYNOVI. Therefore, each time you take a
new pack of ADYNOVI, note the date and lot number (which can be found on the pack after
“Lot”) and keep this information in a safe place.
Talk to your doctor before using ADYNOVI.
There is a rare risk that you may develop an anaphylactic reaction (a sudden and severe allergic
reaction) to ADYNOVI. You must be aware of the early signs of allergic reactions, such as skin rash, hives, wheals, widespread itching, swelling of the lips and
tongue, difficulty breathing, wheezing, tightness in the chest, feeling unwell and dizziness.
These may be early symptoms of anaphylactic shock; other manifestations may include
severe dizziness, loss of consciousness and extreme difficulty breathing.
If any of these symptoms occur, stop the injection immediately and contact your
doctor. Severe symptoms, including difficulty breathing and fainting (or feeling faint)
require immediate emergency treatment.
If you suffer from heart disease, inform your doctor because there is an increased risk of
blood clotting complications.

Patients who develop factor VIII inhibitors
The formation of inhibitors (antibodies) is a known complication that can occur during treatment
with all factor VIII-based medicines. Inhibitors, especially at high levels, prevent the
treatment from working properly and you or your child will be carefully monitored to
check for the development of these inhibitors. If ADYNOVI does not control bleeding in you or
your child, inform your doctor immediately.

Catheter-related complications
If you need a central venous access device (CVAD), you
should consider the risk of complications related to the CVAD, including local infections, the presence of
bacteria in the blood and thrombosis at the catheter site.

Children and adolescents
ADYNOVI can only be used in adolescents and adults (from 12 years of age). The warnings and
precautions listed also apply to adolescents.

Other medicines and ADYNOVI
Tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy and breastfeeding
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are
breastfeeding, ask your doctor for advice before using this medicine. Haemophilia A occurs
only rarely in women. Therefore, no experience is available on the use of ADYNOVI
during pregnancy and breastfeeding.

Driving and using machines
ADYNOVI does not or negligibly alters the ability to drive vehicles or use
machines.

ADYNOVI contains sodium
This medicine contains up to 12.42 mg of sodium (the main component of table salt) per
vial. This is equivalent to 0.62% of the recommended maximum daily intake of
sodium with the diet of an adult. Depending on your body weight and the dose of ADYNOVI, you may
be given more vials. This should be taken into consideration if you are on a low-salt diet.

3. How to use ADYNOVI

Treatment with ADYNOVI must be initiated and supervised by a physician experienced in the
care of patients with hemophilia A.
The physician will calculate your dose of ADYNOVI based on your condition, your weight, and the purpose
for which it is used, i.e., prevention or treatment of bleeding. The frequency of
administration will depend on how effective ADYNOVI is in your case. In general, replacement therapy
with ADYNOVI is a lifelong treatment.
Use this medicine following exactly the instructions of your doctor. If you have doubts, consult your
doctor.
Bleeding prevention
The normal dose of ADYNOVI ranges from 40 to 50 IU per kg of body weight, administered 2 times a
week.
Bleeding treatment
The dose of ADYNOVI is calculated based on body weight and the factor VIII levels that need to be
achieved. The factor VIII levels to be achieved depend on the severity and location of the
bleeding.
If you think that the effect of ADYNOVI is insufficient, contact your doctor.
The doctor will perform the necessary laboratory tests to verify that your factor VIII levels are
adequate. This is particularly important if you are going to undergo major surgery.

Use in children and adolescents
ADYNOVI can only be used in adolescents and adults (12 years and older). Even in
adolescents, the dose is calculated based on body weight and is the same as used for adults.

How ADYNOVI is administered
ADYNOVI is generally injected into a vein (intravenously) by a doctor or nurse.
ADYNOVI can also be administered by you or another person by injection, but only after
detailed instructions for self-administration.

If you use more ADYNOVI than you should
Use ADYNOVI following exactly the instructions of your doctor. If you have doubts, consult your
doctor. If you inject more ADYNOVI than the recommended amount, contact your doctor as soon as possible.

If you forget to use ADYNOVI
Do not inject a double dose to make up for a missed dose. Proceed with the next scheduled
injection and continue according to your doctor's instructions.

If you stop using ADYNOVI
Do not stop using ADYNOVI without consulting your doctor.
If you have any doubts about 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 a sudden and severe allergic reaction(anaphylactic reaction) occurs, stop
immediatelythe injection. Seek medical attention immediatelyif you experience any of the
following initial symptoms of allergic reactions:

• skin rash, urticaria, wheals, generalised itching,
• swelling of the lips and tongue,
• difficulty breathing, wheezing, tightness in the chest,
• feeling unwell,
• dizziness and loss of consciousness.

Serious symptoms, including difficulty breathing and fainting (or feeling faint),
require immediate emergency treatment.
In patients who have received previous treatment with factor VIII (more than 150 days of
treatment), inhibitor antibodies may form (see section 2) with uncommon frequency
(less than 1 in 100 patients). If this happens, the medicine may stop working properly and you
may experience prolonged bleeding. If this happens, you should contact your doctor
immediately.

Very common side effects(may affect more than 1 in 10 people)
Headache

Common side effects(may affect up to 1 in 10 people)
Nausea
Diarrhoea
Skin rash
Dizziness
Urticaria

Uncommon side effects(may affect up to 1 in 100 people)
Flushing, allergic reaction (hypersensitivity)
Factor VIII inhibitors (in patients who have received previous treatment with factor VIII
(more than 150 days of treatment))
Increase in some types of white blood cells
Infusion reaction
Red eyes
Adverse drug skin reaction

Side effects with unknown frequency(frequency cannot be estimated from available data)
Life-threatening reactions (anaphylaxis)

Additional side effects in children
The frequency, type and severity of adverse reactions in children are expected to be the same as those
in adults.

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. You can also report side effects directly through the national reporting system listed
in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store ADYNOVI

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 and on the packaging after
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C)
Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
During the period of validity, the vial of powder can be stored at room temperature
(up to a maximum of 30 °C) for a single period that must not exceed 3 months. In this case, the
medicine will expire at the end of this 3-month period or on the expiry date printed on the
product vial, whichever occurs first. Record the end of the 3-month period at room temperature on the
product packaging. The product cannot be stored again in the refrigerator after having been stored at
room temperature. Do not refrigerate the solution after preparation.
Use the product within 3 hours of complete dissolution of the powder.
The product is for single use only. Dispose of any unused solution appropriately.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What ADYNOVI contains

• The active substance is rurioctocog alfa pegol (coagulation factor VIII human pegylated produced with recombinant DNA technology). Each vial of powder nominally contains 250, 500, 1,000, 2,000, or 3,000 IU of rurioctocog alfa pegol.
• The solvent vial contains 5 mL of water for injections.
• The other components are mannitol, trehalose dihydrate, histidine, glutathione, sodium chloride, calcium chloride dihydrate, tris(hydroxymethyl)aminomethane and polysorbate 80. See section 2 “ADYNOVI contains sodium”.

Description of the appearance of ADYNOVI and content of the pack
ADYNOVI is supplied as a powder and solvent for injection solution (powder for
injection solution). The powder is a friable powder from white to off-white. The solvent is a
clear and colourless solution. After reconstitution the solution appears clear, colourless and free of
foreign particles.
Each pack contains one vial of powder, one vial of solvent and a reconstitution device (BAXJECT II Hi-Flow).

Marketing authorisation holder
Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna

Manufacturer
Baxalta Belgium Manufacturing SA
Boulevard René Branquart 80
B-7860 Lessines
Belgium
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Takeda Belgium NV
Tél/Tel: +32 2 464 06 11
[email protected]

Lietuva
Takeda, UAB
Tel: +370 521 09 070
[email protected]

България
Такеда България ЕООД
Тел.: +359 2 958 27 36
[email protected]

Luxembourg/Luxemburg
Takeda Belgium NV
Tél/Tel: +32 2 464 06 11
[email protected]

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722
[email protected]

Magyarország
Takeda Pharma Kft.
Tel.: +36 1 270 7030
[email protected]

Danmark
Takeda Pharma A/S
Tlf: +45 46 77 10 10
[email protected]

Malta
Τakeda HELLAS S.A.
Tel: +30 210 6387800
[email protected]

Deutschland
Takeda GmbH
Tel: +49 (0)800 825 3325
[email protected]

Nederland
Takeda Nederland B.V.
Tel: +31 20 203 5492
[email protected]

Eesti
Takeda Pharma AS
Tel: +372 6177 669
[email protected]

Norge
Takeda AS
Tlf: +47 800 800 30
[email protected]

Ελλάδα
Τakeda ΕΛΛΑΣ Α.Ε.
Τηλ: +30 210 6387800
[email protected]

Österreich
Takeda Pharma Ges.m.b.H.
Tel: +43 (0) 800-20 80 50
[email protected]

España
Takeda Farmacéutica España S.A.
Tel: +34 917 90 42 22
[email protected]

Polska
Takeda Pharma Sp. z o.o.
Tel.: +48223062447
[email protected]

France
Takeda France SAS
Tél: + 33 1 40 67 33 00
[email protected]

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel: + 351 21 120 1457
[email protected]

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: +385 1 377 88 96
[email protected]

România
Takeda Pharmaceuticals SRL
Tel: +40 21 335 03 91
[email protected]

Ireland
Takeda Products Ireland Ltd
Tel: 1800 937 970
[email protected]

Slovenija
Takeda Pharmaceuticals farmacevtska družba d.o.o.
Tel: + 386 (0) 59 082 480
[email protected]

Ísland
Vistor hf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel: +421 (2) 20 602 600
[email protected]

Italia
Takeda Italia S.p.A.
Tel: +39 06 502601
[email protected]

Suomi/Finland
Takeda Oy
Puh/Tel: 0800 774 051
[email protected]

Κύπρος
Proton Medical (Cyprus) Ltd
Τηλ: +357 22866000
[email protected]

Sverige
Takeda Pharma AB
Tel: 020 795 079
[email protected]

Latvija
Takeda Latvia SIA
Tel: +371 67840082
[email protected]

United Kingdom (Northern Ireland)
Takeda UK Ltd
Tel: +44 (0) 2830 640 902
[email protected]
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu/

Instructions for preparation and administration
For the preparation of the solution, use only the solvent and reconstitution device supplied
with each pack of ADYNOVI. The powder must not be mixed with other medicinal products or
solvents or used with other reconstitution devices.

Instructions for reconstitution

• Do not use after the expiry date stated on the label and the carton.
• Do not use if the BAXJECT II Hi-Flow device, its sterile barrier or its packaging is damaged or shows signs of deterioration.
• 1. Use an aseptic technique (conditions of cleanliness and very low germ content) and a flat work surface during the reconstitution procedure.
• 2. Before use, allow all vials of powder and solvent to reach room temperature (between 15 °C and 25 °C).
• 3. Remove the plastic closing cap from the vials of powder and solvent.
• 4. Clean the rubber stoppers with a swab moistened with alcohol and allow them to dry before use.
• 5. Open the packaging of the BAXJECT II Hi-Flow device by removing the top part without touching the inside (Figure A). Do not remove the device from the packaging.
• 6. Turn the packaging upside down. Press vertically downwards to fully insert the transparent plastic tip through the stopper of the solvent vial (Figure B).
• 7. Grab the edge of the BAXJECT II Hi-Flow packaging and pull the packaging away from the device (Figure C). Do not remove the blue protective cap from the BAXJECT II Hi-Flow device. Do not touch the exposed purple plastic tip.
• 8. Turn the system over so that the solvent vial is on top. Quickly and fully insert the purple plastic tip into the stopper of the powder vial by pressing vertically downwards (Figure D). The vacuum will draw the solvent into the powder vial.
• 9. Gently shake until the powder is completely dissolved. Do not refrigerate after reconstitution.

Figure AFigure BFigure C

Figure DFigure EFigure F

Instructions for injection.

Important note:

• Before administration, inspect the prepared solution for the presence of particulate matter and colour change (the solution must be clear, colourless and free of particles).

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

• 1. Remove the blue protective cap from the BAXJECT II Hi-Flow device (Figure E). Do notdraw air into the syringe.Connect the syringe to the BAXJECT II Hi-Flow device. A Luer-lock syringe is recommended.
• 2. Turn the system over (the powder vial is now on top). Draw the reconstituted solution into the syringe by slowly pulling back the plunger (Figure F).
• 3. Disconnect the syringe; attach a suitable needle and inject intravenously. If a patient needs to receive more than one vial of ADYNOVI, the contents of multiple vials can be drawn into the same syringe. To reconstitute each vial of ADYNOVI with the solvent, a separate BAXJECT II Hi-Flow device must be used.
• 4. Administer over a period of no more than 5 minutes (maximum infusion rate 10 mL/min).
• 5. Dispose of unused solution appropriately.

-------------------------------------------------------------------------------------------------------------------------
The following information is intended exclusively for healthcare professionals:

On-demand treatment
In the event of the following bleeding events, the factor VIII activity should not fall below
the level of activity determined (in % of normal value or in IU/dL) in the corresponding period. The following table can be used as a reference for dosage in
bleeding episodes and surgical procedures.

Table 1: Guide for dosage in bleeding episodes and surgical procedures

Prophylaxis
For long-term prophylaxis, the recommended dose is 40 – 50 IU of ADYNOVI per
kilogram of body weight twice a week with intervals of 3 – 4 days.
Adjustments to doses and intervals between administrations may be considered based on the FVIII levels achieved and individual predisposition to
bleeding.

Paediatric population
The dosage for on-demand treatment in paediatric patients (12 to 18 years) is the same as in adult
patients. Prophylactic treatment for patients from 12 years to < 18 years is the same as in adult patients. The long-term safety of ADYNOVI in children under 12 years of age has not yet been established.
Adjustments to doses and intervals between administrations may be considered based on the FVIII levels achieved and individual predisposition to
bleeding.

ADYNOVI 250 IU / 5 mL powder and solvent for injectable solution, 500 IU / 5 mL powder and solvent for injectable solution, 1 000 IU / 5 mL powder and solvent for injectable solution, 2 000 IU / 5 mL powder and solvent for injectable solution, 3 000 IU / 5 mL powder and solvent for injectable solution

rurioctocog alfa pegol (recombinant human coagulation factor VIII pegylated)
Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, talk to your doctor. See section 4.

Contents of this leaflet

• 1. What ADYNOVI is and what it is used for
• 2. What you need to know before you use ADYNOVI
• 3. How to use ADYNOVI
• 4. Possible side effects
• 5. How to store ADYNOVI
• 6. Contents of the pack and other information

1. What is ADYNOVI and what is it used for

ADYNOVI contains the active substance rurioctocog alfa pegol, human coagulation factor VIII
pegylated. Human coagulation factor VIII has been modified to prolong its duration
of action. Factor VIII is necessary for blood to clot and stop bleeding. In patients
with hemophilia A (congenital deficiency of factor VIII), it is absent or does not act
correctly.
ADYNOVI is used for the treatment and prevention of bleeding in patients aged 12
years and older with hemophilia A (an inherited bleeding disorder caused by a deficiency of
factor VIII).

2. What you need to know before you use ADYNOVI

Do not use ADYNOVI

• if you are allergic to rurioctocog alfa pegol, to octocog alfa or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to mouse or hamster proteins

If you have any doubts, ask your doctor.

Warnings and precautions
It is important to keep track of the lot number of ADYNOVI. Therefore, each time you take a
new pack of ADYNOVI, note the date and lot number (which can be found on the pack after
“Lot”) and keep this information in a safe place.
Talk to your doctor before using ADYNOVI.
There is a rare risk that you may develop an anaphylactic reaction (a sudden and severe allergic
reaction) to ADYNOVI. You must be aware of the early signs of allergic reactions, such as skin
rash, hives, wheals, widespread itching, swelling of the lips and tongue, difficulty breathing,
wheezing, tightness in the chest, feeling unwell and dizziness.
These may be early symptoms of anaphylactic shock; other manifestations may include
severe dizziness, loss of consciousness and extreme difficulty breathing.
If any of these symptoms occur, stop the injection immediately and contact your
doctor. Severe symptoms, including difficulty breathing and fainting (or feeling faint)
require immediate emergency treatment.
If you suffer from heart disease, inform your doctor because there is an increased risk of
blood clot complications.

Patients who develop factor VIII inhibitors
The formation of inhibitors (antibodies) is a known complication that can occur during treatment
with all factor VIII-based medicines. Inhibitors, especially at high levels, prevent the
treatment from working properly and you or your child will be carefully monitored to
check for the development of these inhibitors. If ADYNOVI does not control bleeding in you or
your child, inform your doctor immediately.

Central Venous Access Device (CVAD) complications
If you need a central venous access device (CVAD), you should consider the risk of CVAD-related
complications, including local infections, bloodstream infections and catheter site thrombosis.

Children and adolescents
ADYNOVI can only be used in adolescents and adults (from 12 years of age). The warnings and
precautions listed also apply to adolescents.

Other medicines and ADYNOVI
Tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are
breastfeeding, ask your doctor for advice before using this medicine. Haemophilia A occurs
only rarely in women. Therefore, no experience is available on the use of ADYNOVI
during pregnancy and breastfeeding.

Driving and using machines
ADYNOVI does not or negligibly alters the ability to drive or operate machines.

ADYNOVI contains sodium
This medicine contains up to 12.42 mg of sodium (the main component of table salt) per
vial. This is equivalent to 0.62% of the recommended maximum daily intake of sodium with the diet
for an adult. Depending on your body weight and the dose of ADYNOVI, you may be given
more vials. This should be taken into consideration if you are on a low-salt diet.

3. How to use ADYNOVI

Treatment with ADYNOVI must be initiated and supervised by a physician experienced in the care of patients with hemophilia A.
The physician will calculate your dose of ADYNOVI based on your condition, your weight, and the purpose for which it is used, i.e., prevention or treatment of bleeding. The frequency of administration will depend on how effective ADYNOVI is in your case. Generally, replacement therapy with ADYNOVI is a treatment that lasts for life.
Use this medicine following the doctor's instructions exactly. If you have any doubts, consult your doctor.
Bleeding prevention
The normal dose of ADYNOVI ranges from 40 to 50 IU per kg of body weight, administered 2 times a week.
Bleeding treatment
The dose of ADYNOVI is calculated based on body weight and the factor VIII levels that need to be achieved. The factor VIII levels to be achieved depend on the severity and location of the bleeding.
If you feel that the effect of ADYNOVI is insufficient, contact your doctor.
The doctor will perform the necessary laboratory tests to verify that your factor VIII levels are adequate. This is particularly important if you are going to undergo major surgery.

Use in children and adolescents
ADYNOVI can only be used in adolescents and adults (12 years and older). Even in adolescents, the dose is calculated based on body weight and is the same as used for adults.

How ADYNOVI is administered
ADYNOVI is generally injected into a vein (intravenously) by a doctor or nurse.
ADYNOVI can also be administered by you or another person by injection, but only after detailed instructions for self-administration.

If you use more ADYNOVI than you should
Use ADYNOVI following the doctor's instructions exactly. If you have any doubts, consult your doctor. If you inject more ADYNOVI than the recommended amount, contact your doctor as soon as possible.

If you forget to use ADYNOVI
Do not inject a double dose to make up for a missed dose. Proceed with the next scheduled injection and continue according to the doctor's instructions.

If you stop using ADYNOVI
Do not stop using ADYNOVI without consulting your doctor.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If a sudden and severe allergic reaction(anaphylactic reaction) occurs, stop
immediatelythe injection. Consult your doctor immediatelyif you experience any of the
following initial symptoms of allergic reactions:

• skin rash, urticaria, wheals, generalised itching,
• swelling of the lips and tongue,
• difficulty breathing, wheezing, tightness in the chest,
• feeling unwell,
• dizziness and loss of consciousness.

Serious symptoms, including difficulty breathing and fainting (or feeling faint),
require immediate emergency treatment.
In patients who have received previous treatment with factor VIII (more than 150 days of
treatment) inhibitor antibodies may form (see section 2) with uncommon frequency
(less than 1 in 100 patients). If this happens, the medicine may stop working properly and you
may experience persistent bleeding. If this happens, you should contact your doctor
immediately.

Very common side effects(may affect more than 1 in 10 people)
Headache

Common side effects(may affect up to 1 in 10 people)
Nausea
Diarrhoea
Skin rash
Dizziness
Urticaria

Uncommon side effects(may affect up to 1 in 100 people)
Flushing, allergic reaction (hypersensitivity)
Factor VIII inhibitors (in patients who have received previous treatment with factor VIII
(more than 150 days of treatment))
Increase in some types of white blood cells
Infusion reaction
Red eyes
Adverse drug skin reaction

Side effects with unknown frequency(frequency cannot be estimated from available data)
Life-threatening reactions (anaphylaxis)

Additional side effects in children
The frequency, type and severity of adverse reactions in children are expected to be the same as those
in adults.

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. You can also report side effects directly
through the national reporting system listed
in Annex V. By reporting side effects you can help provide more information
on the safety of this medicine.

5. How to store ADYNOVI

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 and on the pack after
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C)
Do not freeze.
Keep the blister in the outer packaging to protect the medicine from light.
During the period of validity, the powder vial can be stored at room temperature
(up to a maximum of 30 °C) for a single period not exceeding 3 months. In this case, the
medicine will expire at the end of this 3-month period or the expiry date printed on the
product vial, whichever occurs first. Record the end of the 3-month period at room temperature on the
product pack. The product cannot be stored again in the refrigerator after being stored at room
temperature. Do not refrigerate the solution after preparation.
Use the product within 3 hours of complete dissolution of the powder.
The product is for single use only. Dispose of any unused solution appropriately.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What ADYNOVI contains

• The active substance is rurioctocog alfa pegol (coagulation factor VIII human pegylated produced with recombinant DNA technology). Each vial of powder nominally contains 250, 500, 1,000, 2,000, or 3,000 IU of rurioctocog alfa pegol.
• The solvent vial contains 5 mL of water for injections.
• The other components are mannitol, trehalose dihydrate, histidine, glutathione, sodium chloride, calcium chloride dihydrate, tris(hydroxymethyl)aminomethane and polysorbate 80. See section 2, “ADYNOVI contains sodium”.

Description of ADYNOVI and contents of the pack
ADYNOVI is supplied as a powder and solvent for injectable solution (powder for
injectable solution). The powder is a friable powder from white to off-white. The solvent is a
clear and colourless solution. After reconstitution the solution appears clear, colourless and free of
foreign particles.

Marketing Authorisation Holder
Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna

Manufacturer
Baxalta Belgium Manufacturing SA
Boulevard René Branquart 80
B-7860 Lessines
Belgium
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Takeda Belgium NV
Tél/Tel: +32 2 464 06 11
[email protected]

Lietuva
Takeda, UAB
Tel: +370 521 09 070
[email protected]

България
Такеда България ЕООД
Тел.: +359 2 958 27 36
[email protected]

Luxembourg/Luxemburg
Takeda Belgium NV
Tél/Tel: +32 2 464 06 11
[email protected]

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722
[email protected]

Magyarország
Takeda Pharma Kft.
Tel.: +36 1 270 7030
[email protected]

Danmark
Takeda Pharma A/S
Tlf: +45 46 77 10 10
[email protected]

Malta
Τakeda HELLAS S.A.
Tel: +30 210 6387800
[email protected]

Deutschland
Takeda GmbH
Tel: +49 (0)800 825 3325
[email protected]

Nederland
Takeda Nederland B.V.
Tel: +31 20 203 5492
[email protected]

Eesti
Takeda Pharma AS
Tel: +372 6177 669
[email protected]

Norge
Takeda AS
Tlf: +47 800 800 30
[email protected]

Ελλάδα
Τakeda ΕΛΛΑΣ Α.Ε.
Tηλ: +30 210 6387800
[email protected]

Österreich
Takeda Pharma Ges.m.b.H.
Tel: +43 (0) 800-20 80 50
[email protected]

España
Takeda Farmacéutica España S.A.
Tel: +34 917 90 42 22
[email protected]

Polska
Takeda Pharma Sp. z o.o.
Tel.: +48223062447
[email protected]

France
Takeda France SAS
Tél: + 33 1 40 67 33 00
[email protected]

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel: + 351 21 120 1457
[email protected]

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: +385 1 377 88 96
[email protected]

România
Takeda Pharmaceuticals SRL
Tel: +40 21 335 03 91
[email protected]

Ireland
Takeda Products Ireland Ltd
Tel: 1800 937 970
[email protected]

Slovenija
Takeda Pharmaceuticals farmacevtska družba d.o.o.
Tel: + 386 (0) 59 082 480
[email protected]

Ísland
Vistor hf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel: +421 (2) 20 602 600
[email protected]

Italia
Takeda Italia S.p.A.
Tel: +39 06 502601
[email protected]

Suomi/Finland
Takeda Oy
Puh/Tel: 0800 774 051
[email protected]

Κύπρος
Proton Medical (Cyprus) Ltd
Τηλ: +357 22866000
[email protected]

Sverige
Takeda Pharma AB
Tel: 020 795 079
[email protected]

Latvija
Takeda Latvia SIA
Tel: +371 67840082
[email protected]

United Kingdom (Northern Ireland)
Takeda UK Ltd
Tel: +44 (0) 2830 640 902
[email protected]
Further details on this medicinal product are available on the website of the European Medicines
Agency: http://www.ema.europa.eu/

Instructions for preparation and administration
ADYNOVI must not be mixed with other medicinal products or solvents.
Each time ADYNOVI is administered, it is strongly recommended to record the name and
batch number of the product. The blister is provided with detachable labels.

Instructions for reconstitution

• Do not use after the expiry date stated on the label and the carton.
• Do not use if the top is not completely sealed on the blister.
• Do not refrigerate the solution after preparation.
• 1. If the product is still stored in a refrigerator, remove the sealed blister (containing the vials of powder and solvent pre-assembled with the reconstitution system) from the refrigerator and hold it at room temperature (15 °C – 25 °C).
• 2. Wash your hands thoroughly using soap and warm water.
• 3. Open the ADYNOVI blister by removing the top. Remove the BAXJECT III system from the blister.
• 4. Place the powder vial on a flat surface with the solvent vial on top (Figure 1). There is a blue strip on the solvent vial. Do not remove the blue sealing cap until instructed in a subsequent step.
• 5. Holding the powder vial with one hand in the BAXJECT III system, firmly press the solvent vial with the other hand until the system is fully engaged and the solvent flows into the powder vial (Figure 2). Do not tilt the system until the transfer is complete.
• 6. Verify that the solvent transfer is complete. Gently swirl until the substance is completely dissolved (Figure 3). Make sure the powder is completely dissolved, otherwise not all of the reconstituted solution will pass through the filter of the device. The product dissolves quickly (typically in less than 1 minute). After reconstitution, the solution appears clear, colourless and free of foreign particles.

Figure 1Figure 2Figure 3

Figure 4Figure 5

Instructions for injection
During administration, aseptic technique (conditions of cleanliness and
very low germ content) must be used.

Important note:

• Before administration, inspect the prepared solution for the presence of particulate matter and colour change (the solution should be clear, colourless and free of particles). Do not use if the solution is not completely clear or dissolved.

• 1. Remove the blue sealing cap from the BAXJECT III device (Figure 4). Do not draw airinto the syringe. Connect the syringe to the BAXJECT III device. A Luer-lock syringe is recommended.
• 2. Invert the system (the powder vial is now on top). Draw the reconstituted solution into the syringe by slowly pulling back the plunger (Figure 5).
• 3. Disconnect the syringe; attach a butterfly needle to the syringe and inject the reconstituted solution into a vein. The solution should be administered slowly, at a rate determined by the patient’s comfort level, not exceeding 10 mL/min. (See section 4 “Possible side effects”.)
• 4. Dispose of unused solution appropriately.

-------------------------------------------------------------------------------------------------------------------------
The following information is intended exclusively for healthcare professionals:

On-demand treatment
In the event of the following bleeding events, the factor VIII activity must not fall below
the level of activity determined (in % of normal value or in IU/dL) in the corresponding period. The following table can be used as a reference for dosage in
bleeding episodes and surgical procedures.

Table 1: Guide for dosage in bleeding episodes and surgical procedures

Prophylaxis
For long-term prophylaxis, the recommended dose is 40 – 50 IU of ADYNOVI per
kilogram of body weight twice a week with intervals of 3 – 4 days.
Adjustments to doses and intervals between administrations may be considered based on the FVIII levels achieved and individual predisposition to
bleeding.

Paediatric population
The dosage for on-demand treatment in paediatric patients (12 to 18 years) is the same as adult patients.
Prophylactic treatment for patients from 12 years to < 18 years is the same as adult patients. The long-term safety of ADYNOVI in children under 12 years of age has not yet been established.
Adjustments to doses and intervals between administrations may be considered based on the FVIII levels achieved and individual predisposition to
bleeding.

ADYNOVI 250 IU / 2 mL powder and solvent for injectable solution, 500 IU / 2 mL powder and solvent for injectable solution, 1,000 IU / 2 mL powder and solvent for injectable solution

rurioctocog alfa pegol (human coagulation factor VIII recombinant pegylated)
Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Never give it to others, even if their symptoms are the same as yours, as it could be dangerous.
• If any side effects occur, ask your doctor. See section 4.

Contents of this leaflet

• 1. What ADYNOVI is and what it is used for
• 2. What you need to know before you use ADYNOVI
• 3. How to use ADYNOVI
• 4. Possible side effects
• 5. How to store ADYNOVI
• 6. Contents of the pack and other information

1. What is ADYNOVI and what is it used for

ADYNOVI contains the active substance rurioctocog alfa pegol, human coagulation factor VIII
pegylated. Human coagulation factor VIII has been modified to prolong its duration
of action. Factor VIII is necessary for blood to clot and stop bleeding. In patients
with hemophilia A (congenital deficiency of factor VIII) it is either absent or does not act
correctly.
ADYNOVI is used for the treatment and prevention of bleeding in patients aged 12
years and older with hemophilia A (an inherited bleeding disorder caused by a deficiency of
factor VIII).

2. What you need to know before using ADYNOVI

Do not use ADYNOVI

• if you are allergic to rurioctocog alfa pegol, 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 have any doubts, ask your doctor.

Warnings and precautions
It is important to keep track of the lot number of ADYNOVI. Therefore, each time you take a
new package of ADYNOVI, note the date and lot number (which can be found on the package after
“Lot”) and keep this information in a safe place.
Consult your doctor before using ADYNOVI.
There is a rare risk that you may develop an anaphylactic reaction (a sudden and severe allergic
reaction) to ADYNOVI. You must be aware of the early signs of allergic reactions, such as skin rash, hives, wheals, generalized itching, swelling of the lips and
tongue, difficulty breathing, wheezing, tightness in the chest, feeling unwell and dizziness.
These may be early symptoms of anaphylactic shock; other manifestations may include
severe dizziness, loss of consciousness and extreme difficulty breathing.
If any of these symptoms occur, stop the injection immediately and consult a
doctor. Severe symptoms, including difficulty breathing and fainting (or feeling faint)
require immediate emergency treatment.
If you suffer from heart disease, inform your doctor because there is an increased risk of
blood clot complications.

Patients who develop factor VIII inhibitors
The formation of inhibitors (antibodies) is a known complication that can occur during treatment
with all factor VIII-based medicines. Inhibitors, especially at high levels, prevent the
treatment from working properly and you or your child will be carefully monitored to
check for the development of these inhibitors. If ADYNOVI does not control bleeding in you or
your child, inform your doctor immediately.

Catheter-related complications
If you need a central venous access device (CVAD), you should consider the risk of CVAD-related
complications, including local infections, the presence of
bacteria in the blood and thrombosis at the catheter site.

Children and adolescents
ADYNOVI can only be used in adolescents and adults (from 12 years of age). The warnings and
precautions listed also apply to adolescents.

Other medicines and ADYNOVI
Tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding
with breast milk, ask your doctor for advice before using this medicine. Haemophilia A occurs
rarely in women. Therefore, no experience is available on the use of ADYNOVI
during pregnancy and breastfeeding.

Driving and using machines
ADYNOVI does not or negligibly alters the ability to drive vehicles or use
machinery.

ADYNOVI contains sodium
This medicine contains up to 12.42 mg of sodium (the main component of table salt) per
vial. This is equivalent to 0.62% of the maximum recommended daily intake of
sodium with the diet of an adult. Depending on your body weight and the dose of ADYNOVI, you may
be given more vials. This should be taken into consideration if you are following a low-salt diet..

3. How to use ADYNOVI

Treatment with ADYNOVI must be initiated and supervised by a physician experienced in the
care of patients with hemophilia A.
The physician will calculate your dose of ADYNOVI based on your condition, your weight, and the purpose
for which it is used, i.e., prevention or treatment of bleeding. The frequency of
administration will depend on how effective ADYNOVI is in your case. In general, replacement therapy
with ADYNOVI is a treatment that lasts for life.
Use this medicine following exactly the instructions of your doctor. If you have doubts, consult your
doctor.
Prevention of bleeding
The normal dose of ADYNOVI ranges from 40 to 50 IU per kg of body weight, administered 2 times a
week.
Treatment of bleeding
The dose of ADYNOVI is calculated based on body weight and the levels of factor VIII that must be
achieved. The levels of factor VIII to be achieved depend on the severity and location of the
bleeding.
If you feel that the effect of ADYNOVI is insufficient, contact your doctor.
The doctor will perform the necessary laboratory tests to verify that your factor VIII levels are
adequate. This is particularly important if you are going to undergo major surgery.

Use in children and adolescents
ADYNOVI can only be used in adolescents and adults (from 12 years of age). Even in
adolescents, the dose is calculated based on body weight and is the same as used for adults.

How ADYNOVI is administered
ADYNOVI is generally injected into a vein (intravenously) by a doctor or nurse.
ADYNOVI can also be administered by you or another person by injection, but only after
detailed instructions for self-administration.

If you use more ADYNOVI than you should
Use ADYNOVI following exactly the instructions of your doctor. If you have doubts, consult your
doctor. If you inject more ADYNOVI than the recommended amount, contact your doctor as soon as possible.

If you forget to use ADYNOVI
Do not inject a double dose to compensate for a missed dose. Proceed with the next scheduled
injection and continue according to the doctor's instructions.

If you stop using ADYNOVI
Do not stop using ADYNOVI without consulting your doctor.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If a sudden and severe allergic reaction(anaphylactic reaction) occurs, stop
immediatelythe injection. Seek immediate medical attentionif you experience any of the
following initial symptoms of allergic reactions:

• skin rash, urticaria, wheals, generalised itching,
• swelling of the lips and tongue,
• difficulty breathing, wheezing, tightness in the chest,
• feeling unwell,
• dizziness and loss of consciousness.

Serious symptoms, including difficulty breathing and fainting (or feeling faint),
require immediate emergency treatment.
In patients who have received previous treatment with Factor VIII (more than 150 days of
treatment), inhibitor antibodies may form (see section 2) with uncommon frequency
(less than 1 in 100 patients). If this happens, the medicine may stop working properly and you
may experience prolonged bleeding. If this happens, you should contact your doctor
immediately.

Very common side effects(may affect more than 1 in 10 people)
Headache

Common side effects(may affect up to 1 in 10 people)
Nausea
Diarrhoea
Skin rash
Dizziness
Urticaria

Uncommon side effects(may affect up to 1 in 100 people)
Flushing, allergic reaction (hypersensitivity)
Factor VIII inhibitors (in patients who have received previous treatment with Factor VIII
(more than 150 days of treatment))
Increase in some types of white blood cells
Infusion reaction
Red eyes
Adverse drug skin reaction

Side effects with unknown frequency(frequency cannot be estimated based on available
data)
Life-threatening potentially (anaphylaxis)

Additional side effects in children
The frequency, type and severity of adverse reactions in children are expected to be the same as those
in adults.

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. You can also report side effects directly
through the national reporting system listed
in Annex V. By reporting side effects you can help provide more information
on the safety of this medicine.

5. How to store ADYNOVI

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 and on the packaging after
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C)
Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
During the period of validity, the powder vial can be stored at room temperature
(up to a maximum of 30 °C) for a single period that must not exceed 3 months. In this case, the
medicine will expire at the end of this 3-month period or on the expiry date printed on the
product vial, whichever occurs first. Record the end of the 3-month period at room temperature on the
product packaging. The product cannot be stored again in the refrigerator after having been stored at
room temperature. Do not refrigerate the solution after preparation.
Use the product within 3 hours of complete dissolution of the powder.
The product is for single use only. Dispose of any unused solution appropriately.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What ADYNOVI contains

• The active substance is rurioctocog alfa pegol (coagulation factor VIII human pegylated produced with recombinant DNA technology). Each vial of powder nominally contains 250, 500 or 1,000 IU of rurioctocog alfa pegol.
• The solvent vial contains 2 mL of water for injections.
• The other components are mannitol, trehalose dihydrate, histidine, glutathione, sodium chloride, calcium chloride dihydrate, tris(hydroxymethyl)aminomethane and polysorbate 80. See section 2, “ADYNOVI contains sodium”.

Description of the appearance of ADYNOVI and content of the pack
ADYNOVI is supplied as powder and solvent for solution for injection (powder for
solution for injection). The powder is a friable powder from white to off-white. The solvent is a
clear and colourless solution. After reconstitution the solution appears clear, colourless and free of
foreign particles.
Each pack contains one vial of powder, one vial of solvent and a reconstitution device (BAXJECT II Hi-Flow).

Marketing Authorisation Holder
Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna

Manufacturer
Baxalta Belgium Manufacturing SA
Boulevard René Branquart 80
B-7860 Lessines
Belgium
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Takeda Belgium NV
Tél/Tel: +32 2 464 06 11
[email protected]

Lietuva
Takeda, UAB
Tel: +370 521 09 070
[email protected]

България
Такеда България ЕООД
Тел.: +359 2 958 27 36
[email protected]

Luxembourg/Luxemburg
Takeda Belgium NV
Tél/Tel: +32 2 464 06 11
[email protected]

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722
[email protected]

Magyarország
Takeda Pharma Kft.
Tel.: +36 1 270 7030
[email protected]

Danmark
Takeda Pharma A/S
Tlf: +45 46 77 10 10
[email protected]

Malta
Τakeda HELLAS S.A.
Tel: +30 210 6387800
[email protected]

Deutschland
Takeda GmbH
Tel: +49 (0)800 825 3325
[email protected]

Nederland
Takeda Nederland B.V.
Tel: +31 20 203 5492
[email protected]

Eesti
Takeda Pharma AS
Tel: +372 6177 669
[email protected]

Norge
Takeda AS
Tlf: +47 800 800 30
[email protected]

Ελλάδα
Τakeda ΕΛΛΑΣ Α.Ε.
Tηλ: +30 210 6387800
[email protected]

Österreich
Takeda Pharma Ges.m.b.H.
Tel: +43 (0) 800-20 80 50
[email protected]

España
Takeda Farmacéutica España S.A.
Tel: +34 917 90 42 22
[email protected]

Polska
Takeda Pharma Sp. z o.o.
Tel. +48223062447
[email protected]

France
Takeda France SAS
Tél: + 33 1 40 67 33 00
[email protected]

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel: + 351 21 120 1457
[email protected]

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: +385 1 377 88 96
[email protected]

România
Takeda Pharmaceuticals SRL
Tel: +40 21 335 03 91
[email protected]

Ireland
Takeda Products Ireland Ltd
Tel: 1800 937 970
[email protected]

Slovenija
Takeda Pharmaceuticals farmacevtska družba d.o.o.
Tel: + 386 (0) 59 082 480
[email protected]

Ísland
Vistor hf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel: +421 (2) 20 602 600
[email protected]

Italia
Takeda Italia S.p.A.
Tel: +39 06 502601
[email protected]

Suomi/Finland
Takeda Oy
Puh/Tel: 0800 774 051
[email protected]

Κύπρος
Proton Medical (Cyprus) Ltd
Τηλ: +357 22866000
[email protected]

Sverige
Takeda Pharma AB
Tel: 020 795 079
[email protected]

Latvija
Takeda Latvia SIA
Tel: +371 67840082
[email protected]

United Kingdom (Northern Ireland)
Takeda UK Ltd
Tel: +44 (0) 2830 640 902
[email protected]
More detailed information on this medicinal product is available on the website of the European
Medicines Agency: http://www.ema.europa.eu/

Instructions for preparation and administration
For the preparation of the solution, use only the solvent and reconstitution device provided
with each pack of ADYNOVI. The powder must not be mixed with other medicinal products or
solvents or used with other reconstitution devices.

It is strongly recommended that each time ADYNOVI is administered, the name and
batch number of the product are recorded. The powder vial is provided with detachable labels.

Instructions for reconstitution

• Do not use after the expiry date stated on the label and the carton.
• Do not use if the BAXJECT II Hi-Flow device, its sterile barrier or its packaging is damaged or shows signs of deterioration.
• 1. Use an aseptic technique (conditions of cleanliness and very low germ count) and a flat work surface during the reconstitution procedure.
• 2. Before use, allow all vials of powder and solvent to reach room temperature (between 15 °C and 25 °C).
• 3. Remove the plastic closing cap from the powder and solvent vials.
• 4. Clean the rubber stoppers with a swab moistened with alcohol and allow them to dry before use.
• 5. Open the packaging of the BAXJECT II Hi-Flow device by removing the top without touching the inside (Figure A). Do not remove the device from the packaging.
• 6. Turn the packaging upside down. Press down vertically to fully insert the transparent plastic tip through the stopper of the solvent vial (Figure B).
• 7. Grab the edge of the BAXJECT II Hi-Flow packaging and pull the packaging away from the device (Figure C). Do not remove the blue locking cap from the BAXJECT II Hi-Flow device. Do not touch the exposed purple plastic tip.
• 8. Turn the system over so that the solvent vial is on top. Quickly and fully insert the purple plastic tip into the stopper of the powder vial by pressing down vertically (Figure D). The vacuum will draw the solvent into the powder vial.
• 9. Gently shake until the powder is completely dissolved. Do not refrigerate after reconstitution.

Figure AFigure BFigure C

Figure DFigure EFigure F

Instructions for injection

Important note:

• Before administration, inspect the prepared solution for the presence of particulate matter and colour change (the solution must be clear, colourless and free of particles).

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

• 1. Remove the blue locking cap from the BAXJECT II Hi-Flow device (Figure E). Do notdraw air into the syringe.Connect the syringe to the BAXJECT II Hi-Flow device. A Luer-lock syringe is recommended.
• 2. Turn the system over (the powder vial is now on top). Draw the reconstituted solution into the syringe by slowly pulling back the plunger (Figure F).
• 3. Disconnect the syringe; attach a suitable needle and inject intravenously. If a patient needs to receive more than one vial of ADYNOVI, the contents of multiple vials can be drawn into the same syringe. To reconstitute each vial of ADYNOVI with the solvent, a separate BAXJECT II Hi-Flow device must be used.
• 4. Administer over a period of no more than 5 minutes (maximum infusion rate 10 mL/min).
• 5. Dispose of unused solution appropriately.

-------------------------------------------------------------------------------------------------------------------------
The following information is intended exclusively for healthcare professionals:

On-demand treatment
In the event of the following bleeding events, the factor VIII activity must not fall below
the level of activity determined (in % of normal value or in IU/dL) in the corresponding period. The following table can be used as a reference for dosage in
bleeding episodes and surgical interventions.

Table 1:Guidance for dosage in bleeding episodes and surgical interventions

Prophylaxis
For long-term prophylaxis, the recommended dose is 40 – 50 IU of ADYNOVI per
kilogram of body weight twice a week with intervals of 3 – 4 days.
Adjustments to doses and intervals between administrations may be considered based on the FVIII levels achieved and individual predisposition to
bleeding.

Paediatric population
The dosage for on-demand treatment in paediatric patients (12 to 18 years) is the same as in adult patients. Prophylactic treatment for patients from 12 years to < 18 years is the same as in adult patients. The long-term safety of ADYNOVI in children under 12 years of age has not yet been established.
Adjustments to doses and intervals between administrations may be considered based on the FVIII levels achieved and individual predisposition to
bleeding.

ADYNOVI 250 IU / 2 mL powder and solvent for injectable solution, 500 IU / 2 mL powder and solvent for injectable solution, 1 000 IU / 2 mL powder and solvent for injectable solution

rurioctocog alfa pegol (human coagulation factor VIII recombinant pegylated)
Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before you use this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, ask your doctor. See section 4.

Contents of this leaflet

• 1. What ADYNOVI is and what it is used for
• 2. What you need to know before you use ADYNOVI
• 3. How to use ADYNOVI
• 4. Possible side effects
• 5. How to store ADYNOVI
• 6. Contents of the pack and other information

1. What is ADYNOVI and what is it used for

ADYNOVI contains the active substance rurioctocog alfa pegol, human coagulation factor VIII
pegylated. Human coagulation factor VIII has been modified to prolong its duration
of action. Factor VIII is necessary for blood to clot and stop bleeding. In patients
affected by hemophilia A (congenital deficiency of factor VIII) it is either absent or does not act
correctly.
ADYNOVI is used for the treatment and prevention of bleeding in patients aged 12
years and older with hemophilia A (an inherited bleeding disorder caused by a deficiency of
factor VIII).

2. What you need to know before using ADYNOVI

Do not use ADYNOVI

• if you are allergic to rurioctocog alfa pegol, to octocog alfa or to any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to mouse or hamster proteins

If you have any doubts, ask your doctor.

Warnings and precautions
It is important to keep track of the lot number of ADYNOVI. Therefore, each time you take a
new pack of ADYNOVI, note the date and lot number (which can be found on the pack after
“Lot”) and keep this information in a safe place.
Consult your doctor before using ADYNOVI.
There is a rare risk that you may develop an anaphylactic reaction (a sudden and severe allergic
reaction) to ADYNOVI. You must be aware of the early signs of allergic reactions, such as skin rash, urticaria, wheals, generalised itching, swelling of the lips and
tongue, difficulty breathing, wheezing, tightness in the chest, feeling unwell and dizziness.
These may be early symptoms of anaphylactic shock; other manifestations may include
severe dizziness, loss of consciousness and extreme difficulty breathing.
If any of these symptoms occur, stop the injection immediately and consult a
doctor. Severe symptoms, including difficulty breathing and fainting (or feeling faint)
require immediate emergency treatment.
If you suffer from heart disease, inform your doctor because there is an increased risk of
blood clotting complications.

Patients who develop factor VIII inhibitors
The formation of inhibitors (antibodies) is a known complication that can occur during treatment
with all factor VIII-based medicines. Inhibitors, especially at high levels, prevent the
treatment from working properly and you or your child will be closely monitored to
check for the development of these inhibitors. If ADYNOVI does not control bleeding in you or
your child, inform your doctor immediately.

Central Venous Access Device (CVAD) complications
If you need a central venous access device (CVAD), you should consider the risk of CVAD-related
complications, including local infections, bloodstream infections and catheter site thrombosis.

Children and adolescents
ADYNOVI can only be used in adolescents and adults (from 12 years of age). The warnings and
precautions listed also apply to adolescents.

Other medicines and ADYNOVI
Tell your doctor if you are taking, have recently taken or might take any other medicines.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding
with breast milk, ask your doctor for advice before using this medicine. Haemophilia A occurs
rarely in women. Therefore, no experience is available on the use of ADYNOVI
during pregnancy and breastfeeding.

Driving and using machines
ADYNOVI does not or negligibly alters your ability to drive or use
machines.

ADYNOVI contains sodium
This medicine contains up to 12.42 mg of sodium (the main component of table salt) per
vial. This is equivalent to 0.62% of the recommended maximum daily intake of
sodium with the diet of an adult. Depending on your body weight and the dose of ADYNOVI, you may
be given more vials. This should be taken into consideration if you are following a low-salt
diet.

3. How to use ADYNOVI

Treatment with ADYNOVI must be initiated and supervised by a physician experienced in the
care of patients with hemophilia A.
The physician will calculate your dose of ADYNOVI based on your condition, your weight, and the purpose
for which it is used, i.e., prevention or treatment of bleeding. The frequency of
administration will depend on how effective ADYNOVI is in your case. In general, replacement therapy
with ADYNOVI is a treatment that lasts for life.
Use this medicine following the doctor's instructions exactly at all times. If you have any doubts, consult your
doctor.
Bleeding prevention
The normal dose of ADYNOVI ranges from 40 to 50 IU per kg of body weight, administered 2 times a
week.
Bleeding treatment
The dose of ADYNOVI is calculated based on body weight and the levels of factor VIII that need to
be achieved. The levels of factor VIII to be achieved depend on the severity and location of the
bleeding.
If you think the effect of ADYNOVI is insufficient, contact your doctor.
The doctor will perform the necessary laboratory tests to verify that your factor VIII levels are
adequate. This is particularly important if you are going to undergo major surgery.

Use in children and adolescents
ADYNOVI can only be used in adolescents and adults (12 years and older). Even in
adolescents, the dose is calculated based on body weight and is the same as used for adults.

How ADYNOVI is administered
ADYNOVI is generally injected into a vein (intravenously) by a doctor or nurse.
ADYNOVI can also be administered by you or another person by injection, but only after
detailed instructions for self-administration.

If you use more ADYNOVI than you should
Use ADYNOVI following the doctor's instructions exactly at all times. If you have any doubts, consult your
doctor. If you inject more ADYNOVI than the recommended amount, contact your doctor as soon as possible.

If you forget to use ADYNOVI
Do not inject a double dose to make up for a missed dose. Proceed with the next scheduled
injection and continue according to the doctor's instructions.

If you stop using ADYNOVI
Do not stop using ADYNOVI without consulting your doctor.
If you have any doubts about the use of this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If a sudden and severe allergic reaction(anaphylactic reaction) occurs, stop
immediatelythe injection. Consult a doctor immediatelyif you experience any of the
following initial symptoms of allergic reactions:

• skin rash, urticaria, wheals, generalised itching,
• swelling of the lips and tongue,
• difficulty breathing, wheezing, tightness in the chest,
• feeling unwell,
• dizziness and loss of consciousness.

Serious symptoms, including difficulty breathing and fainting (or feeling faint),
require immediate emergency treatment.
In patients who have received previous treatment with factor VIII (more than 150 days of
treatment) inhibitor antibodies may form (see section 2) with uncommon frequency
(less than 1 in 100 patients). If this happens the medicine may stop working properly and you
may experience prolonged bleeding. If this happens, you should contact your doctor
immediately.

Very common side effects(may affect more than 1 in 10 people)
Headache

Common side effects(may affect up to 1 in 10 people)
Nausea
Diarrhoea
Skin rash
Dizziness
Urticaria

Uncommon side effects(may affect up to 1 in 100 people)
Flushing, allergic reaction (hypersensitivity)
Factor VIII inhibitors (in patients who have received previous treatment with factor VIII
(more than 150 days of treatment))
Increase in some types of white blood cells
Infusion reaction
Red eyes
Adverse drug skin reaction

Side effects with unknown frequency(frequency cannot be estimated from available data)
Life-threatening reactions (anaphylaxis)

Additional side effects in children
The frequency, type and severity of adverse reactions in children are expected to be the same as those
in adults.

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. You can also report side effects directly
through the national reporting system listed in Annex V. By reporting side effects you can help
provide more information on the safety of this medicine.

5. How to store ADYNOVI

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 and on the pack after
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C)
Do not freeze.
Keep the blister in the outer packaging to protect the medicine from light.
During the period of validity, the vial of powder can be stored at room temperature
(up to a maximum of 30 °C) for a single period not exceeding 3 months. In this case, the
medicine will expire at the end of this 3-month period or at the expiry date printed on the
product vial, whichever occurs first. Record the end of the 3-month period at room temperature on the
product pack. The product cannot be stored again in the refrigerator after being stored at room
temperature. Do not refrigerate the solution after preparation.
Use the product within 3 hours of complete dissolution of the powder.
The product is for single use only. Dispose of any unused solution appropriately.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What ADYNOVI contains

• The active substance is rurioctocog alfa pegol (coagulation factor VIII human pegylated produced with recombinant DNA technology). Each vial of powder nominally contains 250, 500 or 1,000 IU of rurioctocog alfa pegol.
• The solvent vial contains 2 mL of water for injections.
• The other components are mannitol, trehalose dihydrate, histidine, glutathione, sodium chloride, calcium chloride dihydrate, tris(hydroxymethyl)aminomethane and polysorbate 80. See section 2, “ADYNOVI contains sodium”.

Description of the appearance of ADYNOVI and contents of the pack
ADYNOVI is supplied as powder and solvent for solution for injection (powder for
solution for injection). The powder is a friable powder from white to off-white. The solvent is a
clear and colourless solution. After reconstitution the solution appears clear, colourless and free of
foreign particles.

Marketing Authorisation Holder
Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna

Manufacturer
Baxalta Belgium Manufacturing SA
Boulevard René Branquart 80
B-7860 Lessines
Belgium
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
Takeda Belgium NV
Tél/Tel: +32 2 464 06 11
[email protected]

Lietuva
Takeda, UAB
Tel: +370 521 09 070
[email protected]

България
Такеда България ЕООД
Тел.: +359 2 958 27 36
[email protected]

Luxembourg/Luxemburg
Takeda Belgium NV
Tél/Tel: +32 2 464 06 11
[email protected]

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722
[email protected]

Magyarország
Takeda Pharma Kft.
Tel.: +36 1 270 7030
[email protected]

Danmark
Takeda Pharma A/S
Tlf: +45 46 77 10 10
[email protected]

Malta
Τakeda HELLAS S.A.
Tel: +30 210 6387800
[email protected]

Deutschland
Takeda GmbH
Tel: +49 (0)800 825 3325
[email protected]

Nederland
Takeda Nederland B.V.
Tel: +31 20 203 5492
[email protected]

Eesti
Takeda Pharma AS
Tel: +372 6177 669
[email protected]

Norge
Takeda AS
Tlf: +47 800 800 30
[email protected]

Ελλάδα
Τakeda ΕΛΛΑΣ Α.Ε.
Tηλ: +30 210 6387800
[email protected]

Österreich
Takeda Pharma Ges.m.b.H.
Tel: +43 (0) 800-20 80 50
[email protected]

España
Takeda Farmacéutica España S.A.
Tel: +34 917 90 42 22
[email protected]

Polska
Takeda Pharma Sp. z o.o.
Tel.: +48223062447
[email protected]

France
Takeda France SAS
Tél: + 33 1 40 67 33 00
[email protected]

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel: + 351 21 120 1457
[email protected]

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: +385 1 377 88 96
[email protected]

România
Takeda Pharmaceuticals SRL
Tel: +40 21 335 03 91
[email protected]

Ireland
Takeda Products Ireland Ltd
Tel: 1800 937 970
[email protected]

Slovenija
Takeda Pharmaceuticals farmacevtska družba d.o.o.
Tel: + 386 (0) 59 082 480
[email protected]

Ísland
Vistor hf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel: +421 (2) 20 602 600
[email protected]

Italia
Takeda Italia S.p.A.
Tel: +39 06 502601
[email protected]

Suomi/Finland
Takeda Oy
Puh/Tel: 0800 774 051
[email protected]

Κύπρος
Proton Medical (Cyprus) Ltd
Τηλ: +357 22866000
[email protected]

Sverige
Takeda Pharma AB
Tel: 020 795 079
[email protected]

Latvija
Takeda Latvia SIA
Tel: +371 67840082
[email protected]

United Kingdom (Northern Ireland)
Takeda UK Ltd
Tel: +44 (0) 2830 640 902
[email protected]
More detailed information on this medicinal product is available on the website of the European Medicines
Agency: http://www.ema.europa.eu/

Instructions for preparation and administration
ADYNOVI must not be mixed with other medicines or solvents.
Each time ADYNOVI is administered, it is strongly recommended to record the name and
batch number of the product. The blister is provided with detachable labels.

Instructions for reconstitution

• Do not use after the expiry date stated on the label and the carton.
• Do not use if the top is not completely sealed on the blister.
• Do not refrigerate the solution after preparation.
• 1. If the product is still stored in the refrigerator, remove the sealed blister (containing the powder and solvent vials pre-assembled with the reconstitution system) from the refrigerator and hold it at room temperature (15 °C – 25 °C).
• 2. Wash your hands thoroughly with soap and warm water.
• 3. Open the ADYNOVI blister by removing the top. Remove the BAXJECT III system from the blister.
• 4. Place the powder vial on a flat surface with the solvent vial on top (Figure 1). The solvent vial has a blue strip. Do not remove the blue closure cap until instructed in a subsequent step.
• 5. Holding the powder vial with one hand in the BAXJECT III system, firmly press the solvent vial with the other hand until the system is fully retracted and the solvent flows into the powder vial (Figure 2). Do not tilt the system until the transfer is complete.
• 6. Verify that the solvent transfer is complete. Gently swirl until the substance is completely dissolved (Figure 3). Make sure that the powder is completely dissolved, otherwise not all of the reconstituted solution will pass through the filter of the device. The product dissolves rapidly (typically in less than 1 minute). After reconstitution the solution appears clear, colourless and free of foreign particles.

Figure 1Figure 2Figure 3

Figure 4Figure 5

Instructions for injection
During administration, aseptic technique must be used (conditions of cleanliness and
very low germ content).

Important note:

• Before administration, inspect the prepared solution for the presence of particulate matter and colour change (the solution must be clear, colourless and free of particles). Do not use if the solution is not completely clear or dissolved.

• 1. Remove the blue closure cap from the BAXJECT III device (Figure 4). Do not draw airinto the syringe. Connect the syringe to the BAXJECT III device. A Luer-lock syringe is recommended.
• 2. Invert the system (the powder vial is now on top). Draw the reconstituted solution into the syringe by slowly pulling back the plunger (Figure 5).
• 3. Disconnect the syringe; attach a butterfly needle to the syringe and inject the reconstituted solution into a vein. The solution must be administered slowly, at a rate determined by the patient's comfort level, not exceeding 10 mL/min. (See section 4 “Possible side effects”.)
• 4. Dispose of unused solution appropriately.

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The following information is intended exclusively for healthcare professionals:

On-demand treatment
In the event of the following bleeding events, the factor VIII activity must not fall below
the level of activity plasma determined (in % of normal value or in IU/dL) in the corresponding period. The following table can be used as a reference for dosage in
bleeding episodes and surgical procedures.

Table 1: Guidance for dosage in bleeding episodes and surgical procedures

Prophylaxis
For long-term prophylaxis, the recommended dose is 40 – 50 IU of ADYNOVI per
kilogram of body weight twice weekly with intervals of 3 – 4 days. Dosage adjustments
and intervals between administrations may be considered based on the FVIII levels achieved and individual predisposition to bleeding.

Paediatric population
The dosage for on-demand treatment in paediatric patients (12 to 18 years) is the same as adult patients.
Prophylactic treatment for patients from 12 years to < 18 years is the same as adult patients. The long-term safety of ADYNOVI in children under 12 years of age has not yet been established.
Dosage adjustments and intervals between administrations may be considered
based on the FVIII levels achieved and individual predisposition to bleeding.