Label: information for the user

RIXUBIS250UI Powder andsolvent for injectable solution

RIXUBIS500UI Powder andsolvent for injectable solution

RIXUBIS1000UI Powder andsolvent for injectable solution

RIXUBIS2000UI Powder andsolvent for injectable solution

RIXUBIS3000UI Powder andsolvent for injectable solution

nonacog gamma (recombinant human coagulation factor IX)

Read this label carefully before starting touse this medication because it contains important information for you.

• Keep this label, as you may need to read it again.

• If you have any questions, consult your doctor or pharmacist.

• This medication has been prescribed only for you, andyou should not give it to others, even if they have the same symptoms as you, as it may harm them.

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

1.What is RIXUBIS andfor what it is used

2.What you need to know before starting touse RIXUBIS

3.How to use RIXUBIS

4.Possible adverse effects

5.Storage of RIXUBIS

6.Contents of the package and additional information

RIXUBIS contains the active ingredient nonacog gamma andis a human coagulation factor IX. TheFactor IX is a normal component of human blood necessary for its proper coagulation, RIXUBIS is used in patients with hemophilia B (Christmas disease, a hereditary blood disorder caused by a deficiency of factor IX). It acts by substituting the missing factor IX to allow the patient's blood to coagulate.

RIXUBIS is used for the treatment andprevention of bleeding in patients with hemophilia B of all age groups.

Do not use RIXUBIS

• if you are allergic tononacog gamma or any of the other components of this medication (listed in section6)

• if you are allergic tohamster proteins

Warnings andprecautions

You may experience allergic hypersensitivity reactions with RIXUBIS. Stop the infusion andcontact your doctor or seek urgent medical attention if you experience the first signs of hypersensitivity/allergic reactions such as hives, rash, chest tightness, wheezing, low blood pressure, oranaphylaxis (a severe allergic reaction that can cause difficulty swallowing and/or breathing, red or swollen face and/or hands). Your doctor may need to treat you immediately in case of these reactions. Your doctor may also perform a blood test to check if you have developed neutralizing antibodies (inhibitors) against the medication, as inhibitors can develop along with allergies. Patients with factor IX inhibitors may have a higher risk of anaphylaxis during subsequent treatment with factor IX.

Consult your doctor immediately if bleeding does not stop as expected orif you experience a significant increase in the use of RIXUBIS to control bleeding. Your doctor will perform a blood test to check if you have developed neutralizing antibodies (inhibitors) against RIXUBIS. The risk of developing inhibitors is higher in patients who have not been previously treated with a factor IX substitute medication orin the early stages of treatment, i.e., inyoung children.

The production of factor IX in the body is controlled by the factor IX gene. Patients who have specific mutations in their factor IX gene, such as increased deletion, may be more likely to have factor IX inhibitors andan allergic reaction in the early stages with any factor IX concentrate. Therefore, ifyou know you have such a mutation, your doctor will monitor you more closely to detect signs of an allergic reaction.

If you have liver orcardiac disease, orif you have recently undergone a major surgical procedure, inform your doctor, as there is a higher risk of blood clotting complications.

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

Whenever possible, note the name of the medication andthe batch number each time you use RIXUBIS (e.g., inyour diary) to keep a record of the medications andbatch numbers you have used.

Use of RIXUBIS with other medications

Inform your doctor if you are using, have recently used, ormay need to use any other medication. No interactions of RIXUBIS with other medications have been reported.

Pregnancy, breastfeeding, andfertility

If you are pregnant orbreastfeeding, think you may be pregnant, orintend to become pregnant, consult your doctor before using this medication. Hemophilia B occurs in very rare cases in women.

Driving andusing machines

The influence of RIXUBIS on the ability to drive anduse machines is negligible.

RIXUBIS contains sodium

This medication containsless than 1mmol of sodium (23mg) per vial, i.e., practically no sodium. However, depending on your body weight and your RIXUBIS dose, you may receive more than one vial. This should be taken into account if you follow a low-sodium diet.

The treatment with RIXUBIS will be initiated by a doctor with experience in treating patients with hemophilia B.

Follow exactly the administration instructions of this medication indicated by your doctor. In case of doubt, consult your doctor again.

Your doctor will decide the dose of RIXUBIS to be administered. This dose and duration will depend on the severity of your factor IX deficiency, the location and extent of the bleeding, as well as your clinical status, age, and the speed at which your body consumes factor IX, which should be checked regularly.

Your doctor or nurse will administer RIXUBIS via intravenous infusion (IV) after reconstituting the powder with the provided solvent. You or anyone else can also administer the RIXUBIS injection, but only after receiving proper training.

Reconstitution and Administration

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

• For administration, a luer lock syringe is required.

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

Reconstitution

Use aseptic technique:

1.If the medication is in the refrigerator, remove the vials of RIXUBIS powder and solvent from the refrigerator and wait for them to reach room temperature (between 15°C and 30°C).

2.Wash your hands with soap and warm water.

3.Remove the protectors from the vials of powder and solvent.

4.Clean the stoppers with alcohol wipes. Place the vials on a flat and clean surface.

5.Open the BaxJect II equipment package by removing the paper cap without touching the inside (Fig. a). Do not remove the equipment from the package.

6.Turn the package over and insert the plastic tip through the solvent vial stopper. Hold the package by its end and remove the BaxJect II equipment from its package (Fig. b). Do not remove the blue protector from the BAXJECT II equipment.

7.With BaxJect II attached to the solvent vial, invert the system so that the solvent vial is at the top of the equipment. Insert the white plastic tip into the RIXUBIS powder vial stopper. The vacuum will cause the solvent to penetrate the RIXUBIS powder vial (Fig. c).

8.Agitate gently until all the material has dissolved. The medication dissolves quickly (in about 2 minutes). Ensure that RIXUBIS is completely dissolved, if not, the entire reconstituted solution will not pass through the filter of the equipment. The reconstituted medications should be visually inspected to detect particles or discoloration before administration. The solution should be transparent or slightly opalescent. Do not use turbid or deposit-containing solutions.

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 equipment. Do not introduce air into the syringe. Connect the syringe to the BAXJECT II equipment (Fig. d).

2.Invert the system (the vial with the reconstituted solution at the top). Introduce the reconstituted solution into the syringe, pulling the plunger back slowly (Fig. e).

3.Disconnect the syringe.

4.Connect a perfusion needle with wings to the syringe. Administer by intravenous injection. The solution should be administered slowly, at a speed determined by the patient's comfort level, not exceeding 10 ml per minute.

Fig. dFig. e

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

The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

If you use more RIXUBIS than you should

Follow exactly the administration instructions of RIXUBIS indicated by your doctor. In case of doubt, consult your doctor again. If a higher dose of RIXUBIS than recommended is injected, consult your doctor as soon as possible.

If you forgot to use RIXUBIS

Do not inject a double dose to compensate for the missed doses. Administer the next injection as scheduled and continue as your doctor had indicated.

If you interrupt treatment with RIXUBIS

Do not stop using RIXUBIS without consulting your doctor.

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

Like all medications, this medication may produce adverse effects, although not all people may experience them.

It is possible to experience allergic hypersensitivity reactions with RIXUBIS. These reactions include sensations of burning andprickling at the infusion site, chills, redness, lethargy, restlessness, tingling, hives, itching, andhives, low blood pressure, rapid heart rate, chest tightness, wheezing, throat swelling, anaphylaxis (severe allergic reaction), headache, nausea, andvomiting. Consult your doctor immediately if you experience these symptoms. Your doctor may need to treat you immediately in case of these reactions (see section2‘Warnings andprecautions’).

The following adverse effects have been observed with RIXUBIS:

Frequent Adverse Effects(may affect up to1in every10patients)

• Alteration of taste

• Pain in the extremities.

Adverse Effects of Unknown Frequency(cannot be estimated from available data)

• Allergic reactions (hypersensitivity).

No adverse effects related to excessive blood coagulation (thromboembolic episodes) have been observed with this medication, but may occur with any factor IX product. These include heart attacks, blood clots in the veins orin the lungs.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, evenif it is apossibleadverse effect not listed in this prospectus. You can also report them directly through the national notification system included in theAppendixV. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight andreach of children.

Do not use this medication after the expiration date that appears on the outer packaging and the vial label after CAD. Theexpiration date is the last day of the month indicated.

Store below30°C.

Do not freeze.

Use the reconstituted solution immediately.

Do not use RIXUBIS if the solution is not colorless andtransparent.

Medicines should not be disposed of through drains orin the trash. Ask your pharmacist how to dispose of the containers andmedicines that you no longer need. This will help toprotect the environment.

Composition of RIXUBIS

• The active ingredient is nonacog gamma (human coagulation factor IX recombinant). Each vial contains nominally250,500,1000,2000or3000UI, corresponding to a concentration of50,100,200,400or600UI/ml after reconstitution with5ml of solvent.

• The other components of the powder are sucrose, mannitol, sodium chloride, calcium chloride, L‑histidine, polisorbate80.

Vial of solvent:5ml of sterile water for injectable preparations.

Appearance of the product andcontents of the package

RIXUBIS is provided as powder andsolvent for injectable solution.

The contents of the package are as follows:

• one vial of RIXUBIS powder250,500,1000,2000or3000UI in a glass vial with a rubber stopper
• one vial of5ml of 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

Industriestrasse67

A‑1221Vienna

Tel.:800 66838470
E-mail: [email protected]

Responsible for Manufacturing

Baxalta Belgium Manufacturing SA

Boulevard René Branquart80

B‑7860Lessines

Belgium

Last revision date of this leaflet 01/2020

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

‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑