RIXUBIS 250 IU Proszek i rozpuszczalnik do roztworu do wstrzykiwań

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1. RIXUBIS 250 IU powder and solvent for injectable solution, 500 IU powder and solvent for injectable solution, 1000 IU powder and solvent for injectable solution, 2000 IU powder and solvent for injectable solution, 3000 IU powder and solvent for injectable solution
   1. What is RIXUBIS and what is it used for
   2. What you need to know before using RIXUBIS
   3. How to use RIXUBIS
   4. Possible side effects
   5. How to store RIXUBIS
   6. Content of the pack and other information

RIXUBIS 250 IU powder and solvent for injectable solution, 500 IU powder and solvent for injectable solution, 1000 IU powder and solvent for injectable solution, 2000 IU powder and solvent for injectable solution, 3000 IU powder and solvent for injectable solution

nonacog gamma (recombinant human coagulation factor IX)

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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is RIXUBIS and what is it used for

RIXUBIS contains the active ingredient nonacog gamma and is a coagulation factor IX. Factor IX is a normal component of human blood necessary for effective blood coagulation.
RIXUBIS is used in patients with hemophilia B (Christmas disease, an inherited bleeding disorder caused by a deficiency of factor IX). It acts as a substitute for the missing factor IX to allow the patient's blood to clot.
RIXUBIS is used for the treatment and prevention of bleeding in patients with hemophilia B of all age groups.

2. What you need to know before using RIXUBIS

Do not use RIXUBIS

• if you are allergic to nonacog gamma or to any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to hamster proteins

Warnings and precautions
Hypersensitivity reactions of an allergic type are possible with RIXUBIS. Stop the infusion and
seek immediate medical attention or go to an emergency room if you experience early signs of
hypersensitivity/allergic reactions such as hives, skin rash, a feeling of tightness in the
chest, wheezing, low blood pressure or anaphylaxis (a severe allergic reaction that can cause
difficulty swallowing and/or breathing, redness or swelling of the face and/or hands). Your doctor
may need to treat you promptly for these reactions. Your doctor may also perform a
blood test to check if you have developed antibodies that neutralize the activity (inhibitors) of
this medicine because allergies can develop with inhibitors. Patients with inhibitors
of factor IX may be at increased risk of anaphylaxis during future treatment with
factor IX.
Seek immediate medical attention if bleeding does not stop as expected or if a significantly larger
amount of RIXUBIS is needed to control bleeding.
The doctor will perform a blood test to check if you have developed antibodies that neutralize
the activity (inhibitors) of RIXUBIS. The risk of developing inhibitors is highest in patients who have not
been previously treated with a factor IX replacement product or in the early stages of
treatment, i.e. in young children.
The production of factor IX in the body is controlled by the factor IX gene. Patients who
have specific mutations of the factor IX gene, such as a large deletion, may have a
higher probability of developing factor IX inhibitors and an allergic reaction in the early
period of administration of any factor IX concentrate. Therefore, if the presence of
such a mutation is known, the doctor will perform more careful monitoring to detect signs of an
allergic reaction.
If you suffer from a liver or heart disease or if you have recently undergone major
surgery, inform your doctor because there is an increased risk of blood clotting complications.
Kidney disorders (nephrotic syndrome) have been reported after high doses of factor IX in patients
with hemophilia B with factor IX inhibitors and a history of allergic reactions.
Whenever possible, record (e.g. in your diary) the name and batch number of the product each time
you use RIXUBIS, in order to keep track of the products and batches used.

Other medicines and RIXUBIS
Tell your doctor if you are taking, have recently taken or might take any other
medicines. No interactions of RIXUBIS with other medicines are known.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning a pregnancy, or are breastfeeding
ask your doctor for advice before using this medicine. Hemophilia B is very rare in women.

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

RIXUBIS contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per vial, i.e. it is essentially
“sodium-free”. However, depending on your body weight and your dose of RIXUBIS, you may
receive more than one vial. This should be taken into consideration if you are following a
controlled sodium diet.

3. How to use RIXUBIS

Treatment with RIXUBIS must be initiated by a physician experienced in the care of patients
with hemophilia B.
Use this medicine following exactly the instructions of your doctor. If you have any doubts, consult your
doctor.
It will be up to the doctor to decide the dose of RIXUBIS that will be administered to you. The dose and duration
will depend on the severity of factor IX deficiency, the site and extent of the bleeding, your
clinical condition, age and the rate at which your body uses factor IX, which
must be monitored regularly.
RIXUBIS must be administered by the doctor or nurse by intravenous (IV) infusion
after reconstitution of the powder with the supplied solvent. RIXUBIS can also be administered
by injection by yourself or another person, but only after receiving appropriate
training.
Reconstitution and administration

• For reconstitution, use only the solvent and reconstitution device (BAXJECT II) supplied in the package.
• A luer-lock syringe is required for administration.
• Do not use if the BAXJECT II device, its sterile barrier or its packaging are damaged or show signs of deterioration.

Reconstitution
Use aseptic technique

• 1. If the product is stored in the refrigerator, bring both vials of powder and solvent of RIXUBIS out of the refrigerator and keep them at room temperature (between 15 °C-30 °C).
• 2. Wash your hands thoroughly with soap and warm water.
• 3. Remove the caps from the vials of powder and solvent.
• 4. Clean the caps with cotton swabs soaked in alcohol. Place the vials on a flat and clean surface.
• 5. Open the BAXJECT II device packaging by removing the top without touching the inner surface (Fig. a). Do not remove the device from the packaging.
• 6. Turn the packaging over and insert the transparent plastic tip through the solvent cap. Grab the packaging and pull it away from BAXJECT II (Fig. b). Do not remove the blue cap from the BAXJECT II device.
• 7. With BAXJECT II connected to the solvent vial, turn the system so that the solvent vial is above the device. Insert the white plastic tip through the RIXUBIS cap. The vacuum will draw the solvent into the RIXUBIS vial (Fig. c).
• 8. Gently shake until the substance dissolves. The product dissolves quickly (within 2 minutes). Make sure that the RIXUBIS powder is completely dissolved, otherwise not all of the reconstituted solution will pass through the device filter. Reconstituted medicines must be inspected before administration to detect the presence of any particulate matter and color change. The solution should be clear or slightly opalescent. Do not use turbid solutions or with deposits.

Fig. aFig. bFig. c

Do not refrigerate the preparation after reconstitution.
Use immediately.
Administration
Use aseptic technique

• 1. Remove the blue cap from the BAXJECT II device. Do not draw air into the syringe. Connect the syringe to the BAXJECT II device (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.
• 4. Attach a butterfly needle to the syringe. Inject intravenously. The solution should be administered slowly, at a rate determined by the patient's comfort level, not exceeding 10 ml per minute.

Fig. dFig. e

Whenever possible, record (e.g. in the diary) the name and batch number of the product each time
you use RIXUBIS, in order to track the products and batches of product used.
Unused medicine and waste derived from such medicine must be disposed of in accordance with
current local regulations.

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

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

If you stop using RIXUBIS
Do not stop using RIXUBIS without consulting your doctor.
If you have any doubts about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
With RIXUBIS, hypersensitivity reactions of an allergic type are possible. These reactions may
include sensations of burning and irritation at the infusion site, chills, hot flushes, lethargy,
restlessness, tingling, urticaria, itching and rash, low blood pressure, fast heartbeat, feeling of
tightness in the chest, wheezing, swelling of the throat, anaphylaxis (severe allergic reaction), headache,
nausea and vomiting. If you experience these signs, seek immediate medical attention. The doctor may
need to treat you promptly for these reactions (see
section 2 ‘Warnings and precautions’).
The following side effects have been observed with RIXUBIS:

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

• taste alteration
• pain in the limbs.

Side effects with unknown frequency(frequency cannot be estimated based on available data)

• allergic reactions (hypersensitivity).

No problems related to excessive blood clotting (thromboembolic events) have been found with this
medicine, but they may occur with any product containing
factor IX. These problems may include heart attack, formation of blood clots
in the veins or lungs.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. 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 RIXUBIS

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 outer packaging and on the vial label after Exp. The expiry date refers to the last day of that month.
Store in a refrigerator at a temperature below 30 °C.
Do not freeze.
Use the reconstituted solution immediately.
Do not use RIXUBIS if the solution is not clear and colourless.
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 RIXUBIS contains

• The active substance is nonacog gamma (recombinant human coagulation factor IX). Each vial of powder nominally contains 250, 500, 1000, 2000 or 3000 IU, corresponding to a concentration of 50, 100, 200, 400 or 600 IU/ml after reconstitution with 5 ml of solvent.
• The other components of the powder are sucrose, mannitol, sodium chloride, calcium chloride, L-histidine, polysorbate 80.

Solvent vial: 5 ml of sterile water for injections.

Description of the appearance of RIXUBIS and contents of the pack
RIXUBIS is supplied as powder and solvent for solution for injection.
The contents of the pack are:

• one vial of RIXUBIS 250, 500, 1000, 2000 or 3000 IU powder, glass vial with rubber stopper
• one vial of 5 ml of sterile water for injections, glass vial with rubber stopper
• one BAXJECT II device (needle-free reconstitution device)

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

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
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 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
Τakeda ΕΛΛΑΣ Α.Ε.
Τηλ: +30 210 6387800
[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/.
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The following information is intended exclusively for healthcare professionals:
Treatment monitoring
During treatment, it is recommended to perform an appropriate determination of factor IX levels to establish the dose to be administered and the frequency of infusions. The response of each patient to factor IX is variable, and may exhibit different half-lives and recovery levels. The dose defined based on body weight may require adjustments in underweight or overweight patients. In particular, in the event of major surgery, accurate monitoring of replacement therapy through coagulation analysis (plasma factor IX activity) is essential.
To ensure that the desired level of plasma factor IX activity has been achieved, careful monitoring using an appropriate factor IX activity test is recommended; if necessary, appropriate dose adjustments and frequency of infusions should be made. When using a one-stage in vitrocoagulation test based on activated partial thromboplastin time (aPTT) to determine factor IX activity in patient blood samples, the results of this activity may be significantly affected by both the type of aPTT reagent and the reference standards used in the test itself. This is particularly important when changing laboratories and/or reagents used in the test.
Dosage
The dose and duration of replacement therapy depend on the severity of the factor IX deficiency, the location and extent of the bleeding, the patient's clinical condition, age and factor IX pharmacokinetic parameters, such as incremental recovery and half-life.
The number of units of factor IX administered is expressed in International Units (IU), referenced to the current WHO standard for factor IX-containing products. Plasma factor IX activity is expressed both as a percentage (referenced to normal human plasma) and in International Units (referenced to the international standard for plasma factor IX).
One International Unit of factor IX activity is equivalent to the amount of factor IX contained in one ml of normal human plasma.

Adult population
On-demand treatment:
The calculation of the necessary dose of factor IX is based on the empirical consideration that 1 International Unit of factor IX per kg of body weight increases plasma factor IX activity by 0.9 IU/dl (range 0.5 to 1.4 IU/dl) or 0.9% of normal activity in patients aged 12 years and older (for further information see section 5.2).
The necessary dose is determined using the following formula:
Units
required
= body weight (kg) x desired increase
in factor IX
(%) or (IU/dl)
x reciprocal of
observed recovery (dl/kg)
For an incremental recovery of 0.9 IU/dl per IU/kg, the dose is calculated as follows:
Units
required
= body weight (kg) x desired increase
in factor IX
(%) or (IU/dl)
x 1.1 dl/kg
The amount to be administered and the frequency of administration must always be established based on the clinical efficacy in each individual case.
In the event of the following bleeding events, the factor IX activity should not fall below the activity level (as a percentage of normal value or in IU/dl) determined in the corresponding period. The following table can be used as a reference for dosing in bleeding episodes and in surgery:

Careful monitoring of replacement therapy is particularly important in cases of major surgery or potentially life-threatening bleeding.

Prophylaxis
For long-term prophylaxis of bleeding in patients with severe hemophilia B, the usual doses are 40 - 60 IU of factor IX per kilogram of body weight at intervals of 3 - 4 days for patients aged 12 years and older. In some cases, depending on pharmacokinetics, age, bleeding phenotype and the patient's level of physical activity, shorter administration intervals or higher doses may be necessary.

Continuous infusion
Do not administer RIXUBIS by continuous infusion.

Paediatric population
Patients aged 12 to 17 years:
The dosage is the same for adults and for the paediatric population aged 12 to 17 years.
Patients under 12 years of age:
On-demand treatment
The calculation of the necessary dose of factor IX is based on the empirical consideration that 1 International Unit (IU) of factor IX per kg of body weight increases plasma factor IX activity by 0.7 IU/dl (range 0.31 to 1.0 IU/dl) or 0.7% of normal activity in patients under 12 years of age (for further information see section 5.2).
The necessary dose is determined using the following formula:
Patients under 12 years of age:
Units
required
= body weight (kg) x desired increase
in factor IX
(%) or (IU/dl)
x reciprocal of
observed recovery (dl/kg)
For an incremental recovery of 0.7 IU/dl per IU/kg, the dose is calculated as follows:
Units
required
= body weight (kg) x desired increase
in factor IX
(%) or (IU/dl)
x 1.4 dl/kg
As a reference for dosing in bleeding episodes and in surgery, the same table as for adults can be used (see above).
Prophylaxis:
The recommended dose for paediatric patients under 12 years of age is between 40 and 80 IU/kg at intervals of 3 - 4 days. In some cases, depending on pharmacokinetics, age, bleeding phenotype and the patient's level of physical activity, shorter administration intervals or higher doses may be necessary.