Rixubis 2000 IU/vial powder and solvent for solution for injection

Patient Information Leaflet

Introduction

Patient Information Leaflet

RIXUBIS 250UI Powder and solvent for solution for injection

RIXUBIS 500UI Powder and solvent for solution for injection

RIXUBIS 1000UI Powder and solvent for solution for injection

RIXUBIS 2000UI Powder and solvent for solution for injection

RIXUBIS 3000UI Powder and solvent for solution for injection

nonacog gamma (recombinant human coagulation factor IX)

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.

• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet Contents

1. What RIXUBIS is and what it is 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. Contents of the pack and other information

1. What RIXUBIS is and what it is used for

RIXUBIS contains the active substance nonacog gamma and is a human coagulation factor IX. Factor IX is a normal component of human blood necessary for proper blood coagulation. RIXUBIS is used in patients with haemophilia B (Christmas disease, an inherited blood disorder caused by a deficiency of factor IX). It works by replacing the missing factor IX, enabling the patient's blood to clot.

RIXUBIS is used for the treatment and prevention of bleeding in patients with haemophilia 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

Allergic-type hypersensitivity reactions may occur with RIXUBIS. Stop the infusion and contact your doctor immediately or seek urgent medical attention if you experience early signs of hypersensitivity/allergic reactions such as hives, rash, chest tightness, wheezing, low blood pressure, or anaphylaxis (a severe allergic reaction that may cause difficulty swallowing and/or breathing, redness or swelling of the face and/or hands). Your doctor may need to treat you immediately if these reactions occur. Your doctor may also perform a blood test to check whether you have developed neutralizing antibodies (inhibitors) against the medicine, as inhibitors can develop alongside allergies. Patients with factor IX inhibitors may have an increased risk of anaphylaxis during subsequent treatment with factor IX.

Contact your doctor immediately if bleeding does not stop as expected or if you notice a significant increase in the amount of RIXUBIS needed to control bleeding. Your doctor will perform a blood test to check whether you have developed neutralizing antibodies (inhibitors) against RIXUBIS. The risk of developing inhibitors is higher in patients who have not previously been treated with a factor IX replacement medicine or during the early stages of treatment, particularly in young children.

Factor IX production in the body is controlled by the factor IX gene. Patients who have specific mutations in their factor IX gene, such as a large deletion, may be more likely to develop factor IX inhibitors and allergic reactions early in treatment with any factor IX concentrate. Therefore, if you are known to have such a mutation, your doctor will monitor you more closely for signs of an allergic reaction.

If you have liver or heart disease, or have recently undergone major surgery, inform your doctor, as there is an increased risk of blood clotting complications.

Cases of kidney disorders (nephrotic syndrome) have been reported following administration of high doses of factor IX in patients with hemophilia B who had factor IX inhibitors and a history of allergic reactions.

Whenever possible, record the name of the medicine and the batch number each time you use RIXUBIS (e.g., in your diary) to keep a record of the medicines and batches you have used.

Use of RIXUBIS with other medicines

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines. No interactions between RIXUBIS and other medicines have been reported.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Hemophilia B is very rarely seen in women.

Driving and use of machines

RIXUBIS has no influence on the ability to drive or use machines.

RIXUBIS contains sodium

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

3. How to use RIXUBIS

Treatment with RIXUBIS will be initiated by a physician experienced in the management of patients with haemophilia B.

Always follow exactly your doctor's instructions for using this medicine. If in doubt, consult your doctor again.

Your doctor will decide the dose of RIXUBIS you will receive. This dose and duration of treatment will depend on the severity of your factor IX deficiency, the location and extent of bleeding, as well as your clinical condition, age, and the rate at which your body clears factor IX, which should be monitored regularly.

Your doctor or nurse will administer RIXUBIS by intravenous (IV) infusion after reconstituting the powder with the solvent supplied. You or another person may also administer the RIXUBIS injection, but only after receiving appropriate training.

Reconstitution and administration

• For reconstitution, use only the solvent and reconstitution device (BAXJECT II) provided in the package.

• A luer lock syringe is required for administration.

• Do not use if the BAXJECT II device, the sterile protection system, or its packaging is damaged or shows any signs of deterioration.

Reconstitution

Use aseptic technique:

1. If the medicine has been stored in the refrigerator, remove the RIXUBIS powder and solvent vials from the refrigerator and allow them to reach room temperature (between 15 °C and 30 °C).
2. Wash your hands with soap and lukewarm water.
3. Remove the caps from the powder and solvent vials.
4. Clean the stoppers with alcohol wipes. Place the vials on a clean, flat surface.
5. Open the BaxJect II package by removing the paper lid without touching the inside (Fig. a). Do not remove the device from the package.
6. Turn the package upside down and insert the plastic tip through the solvent vial stopper. Holding the package by its end, remove the BaxJect II device from its packaging (Fig. b). Do not remove the blue protector from the BAXJECT II device.
7. With the BaxJect II attached to the solvent vial, invert the system so that the solvent vial is above the device. Insert the white plastic tip into the stopper of the RIXUBIS powder vial. The vacuum will draw the solvent into the RIXUBIS powder vial (Fig. c).
8. Gently swirl until all material is dissolved. The medicine dissolves rapidly (within approximately 2 minutes). Ensure that RIXUBIS is completely dissolved; otherwise, the entire reconstituted solution may not pass through the device's filter. Reconstituted medicines should be inspected visually for particulate matter or discoloration before administration. The solution should be clear or slightly opalescent. Do not use solutions that are cloudy or contain deposits.

Fig. aFig. bFig. c

Do not refrigerate the preparation after reconstitution.

Use immediately.

Administration

Use aseptic technique:

1. Remove the blue protector from the BAXJECT II device. Do not introduce air into the syringe. Attach the syringe to the BAXJECT II device (Fig. d).
2. Invert the system (the vial with the reconstituted solution on top). Draw the reconstituted solution into the syringe by slowly pulling back the plunger (Fig. e).
3. Disconnect the syringe.
4. Attach a winged infusion needle to the syringe. Administer intravenously. The solution must be given slowly, at a rate determined according to patient comfort, not exceeding 10 ml per minute.

Fig. dFig. e

Whenever possible, record the name of the medicine and the batch number each time you use RIXUBIS (for example, in your diary) to keep a record of the medicines and batches you have used.

Disposal of unused medicine and of all materials that have come into contact with it must be carried out in accordance with local regulations.

If you use more RIXUBIS than you should

Follow exactly the administration instructions for RIXUBIS given by your doctor. If in doubt, consult your doctor again. If you inject a higher dose of RIXUBIS than recommended, consult your doctor as soon as possible.

If you forget to use RIXUBIS

Do not inject a double dose to make up for a missed dose. Administer the next injection as scheduled and continue as directed by your doctor.

If you stop using RIXUBIS

Do not stop using RIXUBIS without consulting your doctor.

If you have any further questions about the use of this medicine, ask your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Allergic-type hypersensitivity reactions may occur with RIXUBIS. These reactions may include burning and stinging sensations at the infusion site, chills, flushing, lethargy, restlessness, tingling, urticarial rash, itching, and rash, low blood pressure, rapid heart rate, chest tightness, wheezing, throat swelling, anaphylaxis (severe allergic reaction), headache, nausea, and vomiting. Consult your doctor immediately if you experience any of these symptoms. Your doctor may need to treat you immediately in case of such reactions (see section 2 'Warnings and precautions').

The following adverse effects have been observed with RIXUBIS:

Frequent adverse effects (may affect up to 1 in 10 patients)

• altered taste
• limb pain

Adverse effects with unknown frequency (cannot be estimated from available data)

• allergic reactions (hypersensitivity)

Problems caused by excessive blood clotting (thromboembolic events) have not been observed with this medicine, but they may occur with any factor IX product. These include heart attacks, blood clots in veins or in the lungs.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of RIXUBIS

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the outer packaging and on the label of the vial after EXP. The expiry date refers to the last day of the month indicated.

Store below 30°C.

Do not freeze.

Use the reconstituted solution immediately.

Do not use RIXUBIS if the solution is not colourless and clear.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of RIXUBIS

• The active substance is nonacog gamma (recombinant human coagulation factor IX). Each vial contains nominally 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 injectable preparations.

Appearance of the product and contents of the pack

RIXUBIS is supplied as a powder and solvent for injectable solution.

The pack contains the following:

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

Marketing Authorization Holder

Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna
Tel.: 800 66838470
E-mail: [email protected]

Manufacturer

Baxalta Belgium Manufacturing SA
Boulevard René Branquart 80
B-7860 Lessines
Belgium

Date of the most recent review of this summary: 01/2020

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

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For an incremental recovery of 0.9 IU/dl per IU/kg, the dose is calculated as follows:

The dose to be administered and the frequency of administration should always be guided by the clinical efficacy in the specific case.

In the case of the following bleeding episodes, factor IX activity should not be less than the given plasma activity level (in % of normal or IU/dL) during the corresponding period. The following table can be used as a guide for dosing in bleeding episodes and surgery:

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

Prophylaxis

For long-term prophylaxis against bleeding in patients with severe haemophilia B, the usual doses are 40 to 60 IU of factor IX per kilogram of body weight administered at intervals of 3 to 4 days for patients aged 12 years and older. In some cases, depending on pharmacokinetic parameters, age, bleeding phenotype, and the patient's physical activity, shorter dosing intervals or higher doses may be required.

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 paediatric patients aged 12 to 17 years.

Patients under 12 years of age:

On-demand treatment:

The calculation of required factor IX dose is based on the empirical finding that 1 international unit 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 additional information, see section 5.2).

The required dosage is determined using the following formula:

Patients under 12 years of age:

For an incremental recovery of 0.7 IU/dl per IU/kg, the dose is calculated as follows:

The same table can be used for adults as a dosing guideline for bleeding episodes and surgery (see above).

Prophylaxis:

The recommended dose range for pediatric patients under 12 years of age is 40 to 80 IU/kg at intervals of 3 to 4 days. In some cases, depending on pharmacokinetic parameters, age, bleeding phenotype, and the patient's physical activity, shorter dosing intervals or higher doses may be required.