ADVATE 250 IU Powder and solvent for injectable solution

Андрій Попов

Доктор Андрій Попов - сімейний лікар зі спеціалізованою підготовкою у сфері лікування хронічного болю. Він проводить відеоконсультації для дорослих в Іспанії та по всій Європі: як для тих, хто вже місяцями живе з болем, який ніхто не зміг чітко пояснити, так і для тих, кому потрібно вирішити проблему зі здоров’ям без очікування кількох тижнів на прийом.

Його підхід простий: уважно вислухати, структурувати ваш випадок і надати практичний план дій, заснований на доказовій медицині та адаптований до вашої медичної історії й індивідуальних потреб.

Біль: у чому він може допомогти

Хронічний біль (понад 3 місяці)
Мігрень і повторювані або інтенсивні головні болі
Біль у шиї, попереку, спині та суглобах
Післятравматичний біль після травм або операцій
Біль неврологічного походження: невралгії, нейропатичний біль, фіброміалгія

Загальна медицина

Часті респіраторні інфекції (застуда, грип, тривалий кашель)
Гіпертонія, діабет і метаболічні порушення
Аналіз лабораторних досліджень та висновків МРТ/КТ (пояснено зрозумілою мовою)
Профілактична медицина та моніторинг здоров’я
Друга думка та корекція лікування (коли це клінічно доцільно)

Як проходить консультація

Кожна сесія триває до 30 хвилин. Розглядаються симптоми, анамнез, ліки та надані обстеження. Наприкінці ви отримуєте чіткий план лікування, визначені подальші кроки та критерії, коли може знадобитися подальший контроль. Якщо виявляються тривожні симптоми, лікар прямо повідомить, чи потрібна очна консультація або невідкладна медична допомога.

Записатися на відеоконсультацію

zł365

Інші варіанти часу

Сторінка містить загальну інформацію. За персональною рекомендацією зверніться до лікаря. У разі гострих або небезпечних симптомів зверніться до екстрених служб.

Інструкція із застосування ADVATE

Зміст інструкції

ADVATE 250 IU Powder and solvent for injectable solution, 500 IU Powder and solvent for injectable solution, 1000 IU Powder and solvent for injectable solution, 1500 IU Powder and solvent for injectable solution, 2000 IU Powder and solvent for injectable solution, 3000 IU Powder and solvent for injectable solution
ADVATE 250 IU Powder and solvent for injectable solution, 500 IU Powder and solvent for injectable solution, 1000 IU Powder and solvent for injectable solution, 1500 IU Powder and solvent for injectable solution, 2000 IU Powder and solvent for injectable solution, 3000 IU Powder and solvent for injectable solution
ADVATE 250 IU Powder and solvent for injectable solution, 500 IU Powder and solvent for injectable solution, 1000 IU Powder and solvent for injectable solution, 1500 IU Powder and solvent for injectable solution
ADVATE 250 IU Powder and solvent for injectable solution, 500 IU Powder and solvent for injectable solution, 1000 IU Powder and solvent for injectable solution, 1500 IU Powder and solvent for injectable solution

ADVATE 250 IU Powder and solvent for injectable solution, 500 IU Powder and solvent for injectable solution, 1000 IU Powder and solvent for injectable solution, 1500 IU Powder and solvent for injectable solution, 2000 IU Powder and solvent for injectable solution, 3000 IU Powder and solvent for injectable solution

octocog alfa (human coagulation factor VIII recombinant)

Read this leaflet carefully before you use this medicine because 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, even those not listed in this leaflet, tell your doctor. See section 4.

Contents of 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 IS ADVATE AND WHAT IT IS USED FOR

ADVATE contains the active substance octocog alfa, human coagulation factor VIII produced
using recombinant DNA technology. Factor VIII is necessary for blood to form a
clot and to stop bleeding. In individuals affected by hemophilia A (congenital factor
VIII deficiency), this is missing or does not function correctly.
ADVATE is used for the treatment and prevention of bleeding in patients of all
age groups with hemophilia A (an inherited bleeding disorder caused by factor VIII deficiency).
ADVATE is prepared without the addition of any human or animal protein during the entire
manufacturing process.

2. WHAT YOU NEED TO KNOW BEFORE USING 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 have any doubts, consult your doctor.

Warnings and precautions
Talk to your doctor before using ADVATE. You must tell your doctor if you have previously
been treated with factor VIII-based medicines, especially if you have developed inhibitors, as
there may be a higher risk of this happening again. Inhibitors are antibodies that inhibit
factor VIII and reduce the effectiveness of ADVATE in preventing and controlling bleeding. The
development of inhibitors is a well-known complication in the treatment of haemophilia A. If
bleeding is not controlled with the use of ADVATE, inform your doctor immediately.
There is a risk, although rare, that you may develop anaphylaxis (a severe and sudden allergic
reaction) to ADVATE. It is important that you recognise the early signs of such allergic reactions,
which include: skin rash, urticaria, blisters, generalised itching, swelling of the lips
and tongue, difficulty breathing, shortness of breath, chest tightness, feeling unwell and dizziness. These
symptoms may be an early sign of anaphylactic shock, whose manifestations may also
include extreme dizziness, loss of consciousness and severe difficulty breathing.
If any of these symptoms occur, stop the injection/infusion
of the medicine immediately and consult your doctor. In case of severe symptoms, including difficulty breathing
and fainting (or feeling faint), emergency medical intervention is necessary.

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 correctly and you or your child will be closely
monitored to check for the development of these inhibitors. If ADVATE does not keep bleeding under control
for you or your child, inform your doctor immediately.

Children and adolescents
The warnings and precautions stated apply to both adults and children
(from 0 to 18 years of age).
Tell your doctor if you are taking, have recently taken or might take any other medicines.
If you are pregnant, suspect you may be pregnant or are planning a pregnancy, or if you are
breastfeeding, ask your doctor for advice before using this medicine.

Driving and using machines
ADVATE does not affect the ability to drive or use machines.

ADVATE contains sodium
This medicine contains 10 mg of sodium (the main component of table salt) per
vial. This is equivalent to 0.5% of the maximum recommended daily intake with the
diet of an adult.

3. HOW TO USE ADVATE

Treatment with ADVATE must be initiated by a physician experienced in the treatment of patients
with haemophilia A.
The physician will determine the dose of ADVATE (in international units or IU) depending on the conditions
physical and body weight, and whether it is used for the prevention or treatment of bleeding.
The frequency of administration will depend on the assessment of the effectiveness of ADVATE in your
case. Generally, replacement therapy with ADVATE lasts for life.
Use this medicine following the doctor's instructions exactly. If you have any doubts, consult your
doctor.
Prevention of bleeding
The usual dose of octocog alfa is between 20 IU and 40 IU per kg of body weight, administered every
2-3 days. However, in some cases, especially for younger patients, more frequent injections or higher doses may be necessary.
Treatment of bleeding
The dose of octocog alfa is calculated based on body weight and the levels of factor VIII that must
be achieved. Optimal factor VIII levels will depend on the severity and location
of the bleeding.
DOSE (IU) = body weight (kg) x desired factor VIII increase (% of normal) x 0.5
If you feel that the effect of ADVATE is insufficient, consult your doctor.
The doctor will perform appropriate laboratory tests to ensure that you have adequate levels of Factor VIII.
This is particularly important if you are to undergo major surgery.

How to take ADVATE
ADVATE is generally injected into a vein (intravenously) by a doctor or nurse.
You or someone else may inject ADVATE, but only after receiving
adequate training. Detailed instructions for self-administration are provided at the end of

If you use more ADVATE than you should
Use ADVATE following the doctor's instructions exactly. If you have any doubts, consult your doctor.
If you take a dose of ADVATE greater than recommended, inform your doctor as soon as
possible.

If you forget to use ADVATE
Do not inject a double dose to make up for a missed dose. Proceed with the injection
next as scheduled and continue as recommended by your doctor.

If you stop taking ADVATE
Do not stop taking ADVATE without first consulting your doctor.
If you have any doubts about the use of this medicine, contact your doctor.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.
In case of serious and sudden allergic reactions(anaphylactic), you must stop
the injection immediately. You must contact your doctor immediatelyif you experience any of
the following early symptoms of allergic reactions):

skin rash, urticaria, blisters (wheals) and widespread itching,
swelling of the lips and tongue,
difficulty breathing, wheezing, tightness in the chest,
general feeling of discomfort,
dizziness, loss of consciousness.

Serious symptoms, such as difficulty breathing and fainting (feeling of lightheadedness), require
prompt emergency treatment.
In children not previously treated with factor VIII-based medicines, the formation of
inhibitor antibodies (see section 2) may be very common (more than 1 in 10); however,
in patients who have received previous treatment with factor VIII (more than 150 days of
treatment) the risk is uncommon (less than 1 in 100). If this happens, the medicine may stop working
properly for you or your child, and you or your child 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)
Factor VIII inhibitors (in children not previously treated with factor VIII-based medicines).

Common side effects(may affect up to 1 in 10 people)
Headache and fever.

Uncommon side effects(may affect up to 1 in 100 people)
Factor VIII inhibitors (in patients who have received previous treatment with factor VIII
(more than 150 days of treatment)), dizziness, influenza, fainting, abnormal heartbeat,
red and itchy swellings on the skin, chest discomfort, bruising at the injection site, injection site
reaction, itching, increased sweating, unusual taste in the mouth,
hot flushes, migraine, memory impairment, chills, diarrhea, nausea, vomiting, shortness of
breath, laryngitis, infection of the lymphatic vessels, paleness of the skin, inflammation of the
eyes, rash, excessive sweating, swelling of the feet and legs, decreased packed cell volume (hematocrit),
increased type of white blood cells (monocytes) and pain in the upper quadrants of the abdomen or in the lower part of the chest.

Related to surgery
Catheter infection, decreased hematocrit, edema of the limbs and joints, prolonged
bleeding after drainage removal, decreased factor VIII level and postoperative hematoma.

Related to central venous access devices (CVAD)
Catheter infection, systemic infection and local blood clot at the catheter site.

Side effects with unknown frequency(frequency cannot be estimated based on available data)
Life-threatening reactions (anaphylaxis) and other allergic reactions (hypersensitivity),
general disorders (fatigue, lack of energy).

Additional side effects in children
In addition to the development of inhibitors in pediatric patients not previously treated (PUP) and
related catheter complications, no age-specific side effect differences have been observed during clinical studies.

Reporting of side effects
If you get any side effects, talk to your doctor. 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 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 period of validity, the vial of powder can be stored at room temperature
(not exceeding 25 °C) for a single period of time not exceeding 6 months. In this case, the
medicine expires at the end of this 6-month period or at the expiry date printed on the
product vial, whichever occurs first. Record the end of the 6-month storage period at room temperature on the external label. The medicine can no longer be stored in the refrigerator after storage at room temperature.
Keep the vial in the outer packaging to protect the medicine from light.
The medicine is for single use. Dispose of any unused residue appropriately.
Use the product immediately after complete dissolution of the lyophilized powder.
Do not refrigerate the solution after preparation.
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 ADVATE contains

The active substance is octocog alfa (Human coagulation Factor VIII produced with recombinant DNA technology). Each vial of powder nominally contains 250, 500, 1000, 1500, 2000 or 3000 IU of octocog alfa.
The other components are mannitol, sodium chloride, histidine, trehalose, calcium chloride, trometamol, polysorbate 80 and glutathione (reduced).

Solvent vial:Water for injections 5 mL

Description of the appearance of ADVATE and contents of the pack
ADVATE is a friable powder of white or off-white color.
After reconstitution, the solution is clear, colorless and free from particulate matter.
Each pack contains a reconstitution device (BAXJECT II).

Marketing Authorisation Holder
Takeda Manufacturing Austria AG
Industriestrasse 67
A-1221 Vienna
Tel: +800 66838470
e-mail: [email protected]

Manufacturers
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
Tel/Tél: +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
Tel/Tél: +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
Drugsales Ltd
Tel: +356 21419070
[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 ΑΕ
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
Tel. + 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

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
Aseptic technique must be used during the preparation and administration of the solution.
Use only water for injections and the reconstitution and preparation devices
supplied in each pack of ADVATE. ADVATE must not be mixed with other medicinal
products or solvents.
It is strongly recommended that each time ADVATE is administered, the name and batch number
of the product are recorded.

Instructions for reconstitution of the solution

Do not use the product after the expiry date stated on the labels and the carton.
Do not use the product if the BAXJECT II device, its sterile barrier system or its packaging are damaged or show any signs of

Do not store the solution in the refrigerator after preparation. deterioration, as indicated by the symbol:

1. If the product is still stored in the refrigerator, bring both ADVATE lyophilized powder and the solvent vial out of the refrigerator and keep them at room temperature (between 15-25 °C).
2. Wash your hands thoroughly using soap and warm water.
3. Remove the caps from the vials of lyophilized powder and solvent.

4. Clean the caps with alcohol-soaked cotton swabs. Place the vials on a clean flat surface.
5. Open the BAXJECT II pack by removing the top part, avoiding touching the inside (Fig. a). Do not remove the device from the pack. Do not use the product if the BAXJECT II device, its sterile barrier system or its packaging are damaged or show any signs of deterioration.
6. Turn the box over, insert the transparent plastic tip through the solvent cap. Grasp the edge of the box and pull it off, releasing the BAXJECT II device (Fig. b). Do not remove the blue cap from the BAXJECT II device. For reconstitution, use only sterile water for injections and the reconstitution device contained in the pack. Holding the BAXJECT II connected to the solvent vial, turn the system over so that the solvent vial is above the device. Insert the white plastic tip through the cap of the ADVATE powder vial. The solvent will be drawn into the ADVATE powder vial (Fig. c.).
8. Gently swirl until dissolved. Make sure that the ADVATE powder is completely dissolved, otherwise not all of the reconstituted solution will pass through the device filter. The product dissolves quickly (usually in less than 1 minute). After reconstitution, the solution appears clear, colorless and free from particulate matter.

Figure aFigure bFigure c

Vials of medicine with rubber stoppers and removable plastic protectors shown in preparation sequence

Instructions for injection
Use a luer-lock syringe for administration.

Important note:

Do not attempt to administer the injection unless you have received specific instructions from medical or nursing personnel.
Check the solution for undissolved material or any abnormal discoloration (the solution must be clear, colorless and free from particulate matter). Do not use ADVATE if the solution is not completely clear or not completely dissolved.

1. Remove the blue cap from BAXJECT II. Do not allow air to enter the syringe. Connect the syringe to the BAXJECT II (Fig. d).
2. Turn the system over (the vial with the reconstituted solution must be on top). Draw the reconstituted solution into the syringe by slowly pulling back the plunger (Fig. e).
3. Disconnect the syringe. Attach the 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 without exceeding 10 mL per minute. (see section 4 "Possible adverse effects").
5. Dispose of unused residues properly.

Figure dFigure e

Glass vial with blue liquid connected to a transparent syringe with a blue plunger and directional arrow

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

Treatment
In the event of the following bleeding episodes, the factor VIII activity must not fall below the levels of activity determined in plasma (in % or in IU/dL) compared to normal levels in the corresponding period. The following table can be used as a reference for dosage in bleeding episodes and in surgery.
The dose and frequency of administration must be adjusted to the clinical response in each individual case. In certain circumstances (e.g. presence of a low-titre inhibitor), higher doses than those calculated using the formula may be necessary.

Severity of bleeding/type of surgical intervention	a Factor VIII level required (%) or (IU/dL)	Frequency of administrations (h)/duration of therapy (days)
Bleeding Early joint bleeding, muscle bleeding or oral bleeding. More extensive joint bleeding, muscle bleeding or hematomas. a i z Life-threatening bleeding.	n a 20-40 i l a t I 30-60 60-100	Repeat the injection every 12-24 hours (8-24 hours for patients under 6 years of age) for at least 1 day until, with cessation of pain, the bleeding episode is resolved or healing is achieved. Repeat the injection every 12-24 hours (8-24 hours for patients under 6 years of age) for 3-4 days or more, until the pain and acute disability have disappeared. Repeat the injection every 8-24 hours (6-12 hours for patients under 6 years of age) until the event is resolved.

Surgical interventions Minor Including dental extractions. Major

30-60 80-100 (pre- and post-intervention)

o Every 24 hours (12-24 hours for patients under 6 years of age), for at least 1 day, c until healing is achieved. a Repeat the injection every 8-24 hours m (6-24 hours for patients under 6 years a of age) until adequate cicatrization is achieved; then continue therapy for at least another 7 days to maintain factor VIII activity at levels between 30-60% (IU/dL).

ADVATE 250 IU Powder and solvent for injectable solution, 500 IU Powder and solvent for injectable solution, 1000 IU Powder and solvent for injectable solution, 1500 IU Powder and solvent for injectable solution, 2000 IU Powder and solvent for injectable solution, 3000 IU Powder and solvent for injectable solution

octocog alfa (recombinant human coagulation factor VIII)

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 you get any side effects, even those not listed in this leaflet, tell your doctor. See section 4.

Contents of 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 IS ADVATE AND WHAT IT IS USED FOR

ADVATE contains the active substance octocog alfa, human coagulation factor VIII produced
with recombinant DNA technology. Factor VIII is necessary for blood to form a
clot and to stop bleeding. In subjects affected by hemophilia A (congenital deficiency of factor
VIII), this is missing or does not function correctly.
ADVATE is used for the treatment and prevention of bleeding in patients of all
age groups with hemophilia A (an inherited bleeding disorder caused by factor VIII deficiency).
ADVATE is prepared without the addition of any human or animal protein during the entire
manufacturing process.

2. WHAT YOU NEED TO KNOW BEFORE USING 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 have any doubts, consult your doctor.

Warnings and precautions
Talk to your doctor before using ADVATE. You must tell your doctor if you have previously
been treated with factor VIII-based medicines, especially if you have developed inhibitors, as
there may be a high risk of this happening again. Inhibitors are antibodies that inhibit
factor VIII and reduce the effectiveness of ADVATE in preventing and controlling bleeding. The
development of inhibitors is a well-known complication in the treatment of hemophilia A. If
bleeding is not controlled with the use of ADVATE, inform your doctor immediately.
There is a risk, although rare, that you may develop anaphylaxis (a severe and sudden allergic
reaction) to ADVATE. It is important that you recognize the early signs of such allergic reactions,
which include: skin rash, hives, blisters, generalized itching, swelling of the lips
and tongue, difficulty breathing, shortness of breath, chest tightness, feeling unwell and dizziness. These
symptoms may be an early sign of anaphylactic shock, whose manifestations may also
include extreme dizziness, loss of consciousness and severe difficulty breathing.
If any of these symptoms occur, stop the injection/infusion of the medicine immediately
and consult your doctor. In case of severe symptoms, including difficulty breathing
and fainting (or feeling faint), emergency medical intervention is necessary.

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 ADVATE does not keep bleeding under control
for you or your child, inform your doctor immediately.

Children and adolescents
The warnings and precautions mentioned apply to both adults and children
(from 0 to 18 years of age).
Tell your doctor if you are taking, have recently taken or might take any other medicines.
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are
breast-feeding, ask your doctor for advice before using this medicine.

Driving and using machines
ADVATE does not impair the ability to drive or use machines.

3. HOW TO USE ADVATE

Treatment with ADVATE must be initiated by a physician experienced in the treatment of patients
with hemophilia A.
The physician will determine the dose of ADVATE (in international units or IU) depending on the conditions
physical and body weight, and whether it is used for prevention or treatment of bleeding.
The frequency of administration will depend on the assessment of the effectiveness of ADVATE in your
case. Generally, replacement therapy with ADVATE lasts for life.
Use this medicine following the doctor's instructions exactly at all times. If you have any doubts, consult your
doctor.
Prevention of bleeding
The usual dose of octocog alfa is between 20 IU and 40 IU per kg of body weight, administered every
2-3 days. However, in some cases, especially for younger patients, more frequent injections or higher doses may be necessary.
Treatment of bleeding
The dose of octocog alfa is calculated based on body weight and the levels of factor VIII that must
be achieved. Optimal factor VIII levels will depend on the severity and location
of the bleeding.
DOSE (IU) = body weight (kg) x desired factor VIII increase (% of normal) x 0.5
If you feel that the effect of ADVATE is insufficient, consult your doctor.
The doctor will perform appropriate laboratory tests to ensure that you have adequate levels of Factor VIII.
This is particularly important if you are to undergo major surgery.

HowADVATE
ADVATE is generally injected into a vein (intravenously) by a doctor or nurse.
You or someone else may administer the ADVATE injection, but only after receiving
adequate training. Detailed instructions for self-administration are provided at the end of

If you use more ADVATE than you should
Use ADVATE following the doctor's instructions exactly at all times. If you have any doubts, consult your doctor.
If you take a dose of ADVATE greater than the recommended dose, inform your doctor as soon as
possible.

If you forget to use ADVATE
Do not inject a double dose to make up for a missed dose. Proceed with the injection
next as scheduled and continue as recommended by your doctor.

If you stop using ADVATE
Do not stop taking ADVATE without first consulting your doctor.
If you have any doubts about the use of this medicine, contact your doctor.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.
In case of severe and sudden allergic reactions(anaphylactic), you must stop
the injection immediately. You must contact your doctor immediatelyif you experience any of
the following early symptoms of allergic reactions):

skin rash, urticaria, blisters (wheals) and widespread itching,
swelling of the lips and tongue,
difficulty breathing, wheezing, tightness in the chest,
general feeling of discomfort,
dizziness, loss of consciousness.

Serious symptoms, such as difficulty breathing and fainting (feeling faint), require
prompt emergency treatment.
In children not previously treated with factor VIII-based medicines, the formation of
inhibitor antibodies (see section 2) may be very common (more than 1 in 10); however,
in patients who have received previous treatment with factor VIII (more than 150 days of
treatment) the risk is uncommon (less than 1 in 100). If this happens, the medicine may stop working
properly for you or your child, and you or your child 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)
Factor VIII inhibitors (in children not previously treated with factor VIII-based medicines).

Common side effects(may affect up to 1 in 10 people)
Headache and fever.

Uncommon side effects(may affect up to 1 in 100 people)
Factor VIII inhibitors (in patients who have received previous treatment with factor VIII
(more than 150 days of treatment)), dizziness, influenza, fainting, abnormal heartbeat,
reddened and itchy swellings on the skin, chest discomfort, bruising at the injection site, injection
site reaction, itching, increased sweating, unusual taste in the mouth,
hot flushes, migraine, memory impairment, chills, diarrhea, nausea, vomiting, shortness of
breath, laryngitis, lymphatic vessel infection, skin pallor, eye inflammation, rash, excessive
sweating, swelling of the feet and legs, decreased packed cell volume (hematocrit), increased
type of white blood cells (monocytes) and pain in the upper quadrants of the abdomen or lower chest.

Related to surgery
Catheter infection, decreased hematocrit, edema of the limbs and joints, prolonged
bleeding after drainage removal, decreased factor VIII level and postoperative hematoma.

Related to central venous access devices (CVAD)
Catheter infection, systemic infection and local blood clot at the catheter site.

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

Additional side effects in children
In addition to the development of inhibitors in previously untreated pediatric patients (PUP) and
catheter-related complications, no age-specific differences in side effects have been observed during
clinical studies.

Reporting of side effects
If you get any side effects, talk to your doctor. 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 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 Expiry. The expiry
date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C).
Do not freeze.
During the period of validity, the blister with the product can be stored at room temperature
(not exceeding 25 °C) for a single period of time not exceeding 6 months. In this case, the
medicine expires at the end of this 6-month period or on the expiry date printed on the blister, whichever
occurs first. Record the end of the 6-month storage period at room temperature on the outer label. The medicine can no longer be stored in
a refrigerator after storage at room temperature.
Keep the blister with the product in the outer packaging to protect the medicine from light.
The medicine is for single use. Dispose of any unused residue appropriately.
Use the product immediately after complete dissolution of the lyophilized powder.
Do not refrigerate the solution after preparation.
Do not dispose of any medicine in the 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 ADVATE contains

The active substance is octocog alfa (Human coagulation Factor VIII produced with recombinant DNA technology). Each vial of powder nominally contains 250, 500, 1000, 1500, 2000 or 3000 IU of octocog alfa.
The other components are mannitol, sodium chloride, histidine, trehalose, calcium chloride, trometamol, polysorbate 80 and glutathione (reduced).

Solvent vial:Water for injections 5 mL

Description of ADVATE and contents of the pack
ADVATE is a friable powder, white or off-white in colour.
After reconstitution, the solution is clear, colourless and free from particulate matter.