Rixubis 2000 IU/vial powder and solvent for injectable solution

2. What you need to know before you use RIXUBIS

Do not use RIXUBIS

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

• if you are allergic to hamster proteins

Warnings andprecautions

It is possible that allergic-type hypersensitivity reactions may occur with RIXUBIS. Stop the infusion and contact your doctor immediately 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, or anaphylaxis (a severe allergic reaction that can cause difficulty swallowing and/or breathing, red and/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 medicine, 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 the bleeding does not stop as expected or if you experience a significant increase in the use of RIXUBIS to control a bleed. 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 medicine or in the early stages of treatment, i.e., in the case of young 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 a large deletion, may be more likely to have factor IX inhibitors and an allergic reaction in the early stages 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 if you have recently undergone major surgery, inform your doctor, as there is a higher risk of complications in blood coagulation.

There have been reports of kidney disorders (nephrotic syndrome) after 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.

Using RIXUBIS with other medicines

Tell your doctor if you are using, have recently used, or might use any other medicines. No interactions of RIXUBIS with other medicines have been reported.

Pregnancy, breastfeeding, andfertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before using this medicine. Hemophilia B occurs very rarely in women.

Driving andusing machines

RIXUBIS has no influence on the ability to drive and 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 your 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 started by a doctor experienced in the treatment of patients with hemophilia B.

Follow exactly the administration instructions of this medicine given by your doctor. If you are unsure, consult your doctor again.

Your doctor will decide the dose of RIXUBIS that will be administered to you. 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 condition, age, and the rate at which your body consumes factor IX, which should be checked regularly.

Your doctor or nurse will administer RIXUBIS to you by intravenous (IV) infusion after reconstituting the powder with the supplied solvent. You or any other person can also administer the injection of RIXUBIS, but only after receiving adequate training.

Reconstitution and administration

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

• For administration, a luer lock syringe is required.

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

Reconstitution

Use aseptic technique:

1. If the medicine is in the refrigerator, remove the RIXUBIS powder and solvent vials from the refrigerator and let them reach room temperature (between 15°C and 30°C).
2. Wash your hands with soap and warm water.
3. Remove the protectors from the powder and solvent vials.
4. Clean the stoppers with the alcohol-impregnated wipes. Place the vials on a flat and clean surface.
5. Open the BaxJect II equipment packaging by removing the paper cover without touching the inside (Fig. a). Do not remove the equipment from its packaging.
6. Turn the packaging over and insert the plastic tip through the solvent stopper. Hold the packaging by its end and remove the BaxJect II equipment from its packaging (Fig. b). Do not remove the blue protector from the BAXJECT II equipment.
7. With BaxJect II attached to the solvent vial, turn the system over so that the solvent vial is on top of the equipment. Insert the white plastic tip into the RIXUBIS powder vial stopper. The vacuum will draw the solvent into the RIXUBIS powder vial (Fig. c).
8. Gently swirl until all the material is dissolved. The medicine dissolves quickly (in about 2 minutes). Make sure RIXUBIS is completely dissolved; if not, the reconstituted solution will not pass through the filter of the equipment. Reconstituted medicines should be inspected visually for particles or discoloration before administration. The solution should be clear or slightly opalescent. Do not use cloudy or precipitated 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. Turn the system over (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. Connect a winged infusion 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 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.

The disposal of unused medicine and all materials that have been in 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 given by your doctor. If you are unsure, 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 forgotten doses. Administer the next injection as scheduled and continue as your doctor has instructed.

If you stop using RIXUBIS

Do not stop using RIXUBIS without consulting your doctor.

If you have any further questions on the use of 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.

It is possible that allergic-type hypersensitivity reactions may occur with RIXUBIS. These reactions include burning and stinging at the infusion site, chills, flushing, lethargy, restlessness, tingling, hives, 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 these signs. Your doctor may need to treat you immediately in case of 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)

• altered taste

• pain in the limbs.

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

• allergic reactions (hypersensitivity).

No problems caused by excessive blood coagulation (thromboembolic events) have been observed with this medicine, but they can occur with any factor IX product. These include heart attacks, blood clots in the veins or lungs.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side 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 which is stated on the outer packaging and on the vial label after EXP. The expiry date is the last day of the month stated.

Store below 30°C.

Do not freeze.

Use the reconstituted solution immediately.

Do not use RIXUBIS if the solution is not colorless and transparent.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Content and Additional Information

RIXUBIS Composition

• The active ingredient 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, and polysorbate 80.

Solvent vial: 5 ml of sterile water for injectable preparations.

Product Appearance andContainer Content

RIXUBIS is provided as a powder and solvent for solution for injection.

The container content is as follows:

• a vial of RIXUBIS powder 250, 500, 1000, 2000, or 3000 IU in a glass vial with a rubber stopper
• a vial of 5 ml of sterile water for injectable preparations in a glass vial with a rubber stopper
• a BAXJECT II (needleless 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 Last Revision of this Prospectus 01/2020

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

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This information is intended solely for healthcare professionals:

Treatment Monitoring

During treatment, it is recommended to determine the appropriate levels of factor IX to calculate the dose to be administered and the frequency of repeated infusions. Individual patients may differ in their response to factor IX with different half-lives and recoveries. The dose based on body weight may require adjustment in patients with low weight or overweight. In the particular case of major surgical interventions, precise monitoring of replacement therapy through coagulation analysis (plasma factor IX activity) is essential.

To ensure that the desired plasma level of factor IX activity has been achieved, it is recommended to perform thorough monitoring using an appropriate factor IX activity assay, and if necessary, to apply the appropriate adjustments to the dose and frequency of repeated infusions. When using the in vitro coagulation assay in one stage based on the activated partial thromboplastin time (aPTT) to determine factor IX activity in patient blood samples, the results of factor IX activity may be significantly affected by the type of aPTT reagent and reference standard used in the assay. This is especially important when changing the laboratory and/or reagents used in the assay.

Posology

The dose and duration of replacement therapy depend on the severity of the factor IX deficiency, the location and extent of the hemorrhage, as well as the patient's clinical condition, age, and pharmacokinetic parameters of factor IX, such as incremental recovery and half-life.

The number of units of factor IX administered is expressed in international units (IU), which are related to the current WHO standard for factor IX products. Factor IX activity in plasma is expressed as a percentage (relative to normal human plasma) or in international units (relative to an international standard for factor IX in plasma).

One international unit of factor IX activity is equivalent to the amount of factor IX present in one milliliter of normal human plasma.

Adult Population

On-demand Treatment: The calculation of the required dose of factor IX is based on the empirical finding that 1 international unit of factor IX per kilogram of body weight increases the factor IX activity of plasma by 0.9 IU/dl (range of 0.5 to 1.4 IU/dl) or 0.9% of normal activity in patients 12 years of age and older (for additional information, see section 5.2).

The required dose is determined using the following formula:

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

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

In the case of the following hemorrhagic 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 dosing guide for hemorrhagic episodes and surgery:

It is especially important to carefully monitor replacement therapy in cases of major surgery or potentially life-threatening hemorrhage.

Prophylaxis

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

Continuous Infusion

Do not administer RIXUBIS by continuous infusion.

Pediatric Population

Patients 12 to 17 years of age:

The posology is the same for adults and pediatric patients 12 to 17 years of age.

Patients under 12 years of age:

On-demand Treatment:

The calculation of the required dose of factor IX is based on the empirical finding that 1 international unit of factor IX per kilogram of body weight increases the factor IX activity of plasma by 0.7 IU/dl (range of 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 dose 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 for adults can be used as a dosing guide for hemorrhagic episodes and surgery (see above).

Prophylaxis:

The recommended dosing interval 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, hemorrhage phenotype, and patient physical activity, shorter dosing intervals or higher doses may be required.