Refixia

Package leaflet: Information for the user

Refixia 500 IU powder and solvent for solution for injection, 1,000 IU powder and solvent for solution for injection, 2,000 IU powder and solvent for solution for injection, 3,000 IU powder and solvent for solution for injection

pegylated nonacog beta
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read all of this leaflet carefully before using 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor. See section 4.

Contents of this leaflet

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

1. What Refixia is and what it is used for

What Refixia is
Refixia contains the active substance pegylated nonacog beta. It is a prolonged-action version of factor IX. Factor IX is a protein naturally present in the blood that helps stop bleeding.
What Refixia is used for
Refixia is used in patients of all age groups with haemophilia B (congenital factor IX deficiency) for the treatment and prevention of bleeding episodes (bleeding).
In patients with haemophilia B, factor IX is missing or does not work properly. Refixia replaces this poorly functioning or absent factor IX and helps blood to form clots at the site of bleeding.

2. What you need to know before using Refixia

Do not use Refixia

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

If you are unsure whether the above applies to you, contact your doctor before using this
medicine.
Warnings and precautions
Traceability
It is important to keep a record of the batch numbers of Refixia. Therefore, each time you start a new
pack of the medicine, write down the date and the batch number (found on the packaging after
Batch) and keep this information in a safe place.
Allergic reactions and development of inhibitors
There is a risk, although rare, that you may develop a severe and sudden allergic reaction (e.g.,
anaphylactic reaction) to Refixia. Stop the injection and contact your doctor or go to the emergency
department immediately if you experience signs of an allergic reaction, such as rash, hives, welts,
generalized itching, redness and/or swelling of the lips, tongue, face or hands, difficulty swallowing or
breathing, shortness of breath, wheezing, tightness in the chest, pale and cold skin, rapid heartbeat and/or
dizziness.
Your doctor may need to treat these reactions promptly and may also perform a blood test to check
whether you have developed factor IX inhibitors (neutralizing antibodies) against the medicine, as
inhibitors may develop alongside allergic reactions. If you develop these inhibitors, you may be at
increased risk of experiencing sudden and severe allergic reactions (e.g., anaphylactic reaction) during
future treatment with factor IX.
Due to the risk of allergic reactions to factor IX, initial treatment with Refixia should be administered in
a medical center or under the supervision of healthcare professionals in a setting where appropriate
medical care can be provided in case of an allergic reaction, if necessary.
Contact your doctor immediately if bleeding does not stop as expected or if you need to significantly
increase the amount of Refixia to control bleeding. Your doctor will perform a blood test to check
whether you have developed inhibitors (neutralizing antibodies) against Refixia. The risk of developing
inhibitors is highest in individuals who have never previously received factor IX-containing medicines,
typically in young children.
Blood clots
Contact your doctor if any of the following situations apply to you, as you may be at higher risk of
developing blood clots during treatment with Refixia:

• you have recently undergone surgery
• you have other serious illnesses, e.g., liver disease, heart disease or cancer
• you have risk factors for heart disease, e.g., high blood pressure, obesity or smoking.

Kidney disorder (nephrotic syndrome)
There is a rare risk of developing a specific kidney disorder called 'nephrotic syndrome' after
administration of high doses of factor IX in patients with haemophilia B who have developed factor IX
inhibitors and have a history of allergic reactions.
Catheter-related problems
If you have a central venous access device (CVC), you may develop infections or blood clots at the
catheter site.
Other medicines and Refixia
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding,
consult your doctor before using Refixia.
Driving and using machines
Refixia does not affect the ability to drive or operate machinery.
Refixia contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e., essentially 'sodium-free'. In the
case of treatment with multiple vials, the total sodium content should be taken into account.

3. How to use Refixia

Treatment with Refixia must be initiated by a physician experienced in the management of patients with haemophilia B. Always use this medicine exactly as instructed by your doctor. If you have any doubts about how to use Refixia, consult your doctor.

Your doctor will determine the appropriate dose for you based on your body weight and the intended treatment purpose.

Prevention of bleeding episodes
The usual dose of Refixia is 40 international units (IU) per kg of body weight, administered once weekly. Your doctor may choose a different dose or adjust the frequency of administration according to your individual needs.

Treatment of bleeding episodes
The usual dose of Refixia is 40 international units (IU) per kg of body weight. Depending on the location and severity of the bleeding, you may require a higher dose (80 IU per kg) or additional injections. Contact your doctor to determine the appropriate dose and number of injections needed.

Use in children and adolescents
Refixia can be used in children and adolescents of all ages. In children and adolescents, the dose is also based on body weight and is the same as that for adults.

How Refixia is administered
Refixia is supplied as a powder and solvent that are mixed to form a solution (reconstitution) and is administered by intravenous injection. For further information, see 'Instructions for using Refixia'.

If you use more Refixia than you should
If you administer more Refixia than prescribed, inform your doctor immediately.
Seek immediate medical advice if you need to significantly increase the amount of Refixia to control a bleeding episode. For further information, see section 2, 'Allergic reactions and development of inhibitors'.

If you forget to use Refixia
If you miss a dose, administer the missed dose as soon as you remember. Do not inject a double dose to make up for the missed dose. If you have any doubts, consult your doctor.

If you stop using Refixia
If you discontinue treatment with Refixia, you may no longer be protected against bleeding episodes, and subsequent bleeding may not stop. Do not stop treatment with Refixia without first consulting your doctor.

If you have any questions about how to use this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Allergic reactions may occur with this medicine.
If you experience sudden and severe allergic reactions (e.g. anaphylactic reactions), you must immediately stop the injection. If you notice any early signs of a serious allergic reaction (anaphylactic reaction), contact your doctor or emergency services immediately:

• difficulty swallowing or breathing
• shortness of breath or wheezing
• tightness in the chest
• redness and/or swelling of the lips, tongue, face, or hands
• skin rash, hives, welts, or itching
• pale and cold skin, rapid heartbeat, and/or dizziness (low blood pressure).

In children who have not previously been treated with factor IX-containing medicines, inhibitors may commonly develop (up to 1 in 10 patients) (see section 2). If this occurs, the medicine may no longer work properly and the child may experience persistent bleeding. In this case, contact your doctor immediately.
The following side effects have been observed with Refixia:
Common side effects (may occur in up to 1 in 10 people)

• allergic reactions (hypersensitivity). These could become severe and potentially life-threatening (anaphylactic reactions).
• itching
• skin reactions at the injection site
• nausea
• fatigue
• skin rash
• children previously untreated with factor IX-containing medicines: neutralizing antibodies (inhibitors), anaphylactic reactions.

Uncommon side effects (may occur in up to 1 in 100 people)

• palpitations
• hot flushes.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. 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 Refixia

Keep this medicine out of the sight and reach of children.
Do not use Refixia after the expiry date stated on the carton and on the labels of the vial and the prefilled syringe after 'Exp.'. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C). Do not freeze. Keep the vial in the outer packaging to protect the medicine from light.
Refixia may be kept outside the refrigerator for a maximum period of 1 year and stored at room temperature (up to 30 °C). Record on the packaging the date when Refixia is removed from the refrigerator and stored at room temperature. This new expiry date must never exceed the original expiry date stated on the outer packaging. Discard the medicine if it is not used before this new expiry date. After storage at room temperature, the medicine must not be returned to the refrigerator.
Use the injectable preparation immediately after reconstituting the solution. If it cannot be used immediately, use it within 24 hours if stored in a refrigerator at 2 °C – 8 °C or within 4 hours if stored outside the refrigerator at a maximum temperature of 30 °C.
The powder in the vial appears white to off-white. Do not use the powder if there has been any change in colour.
The reconstituted solution is clear and colourless or slightly yellow. Do not use the reconstituted solution if you notice particles or changes in colour.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Refixia contains

• The active substance is pegylated nonacog beta (pegylated human coagulation factor IX (rDNA)). Each vial of Refixia contains nominally 500 IU, 1,000 IU, 2,000 IU, or 3,000 IU of pegylated nonacog beta, corresponding to approximately 125 IU/mL, 250 IU/mL, 500 IU/mL, or 750 IU/mL, respectively, after reconstitution with histidine solvent.
• The other components of the powder are sodium chloride, histidine, sucrose, polysorbate 80, mannitol, sodium hydroxide, and hydrochloric acid. See section 2 “Refixia contains sodium”.
• The components of the sterile solvent are histidine, water for injections, sodium hydroxide, and hydrochloric acid.

Description of the appearance of Refixia and contents of the pack

• Refixia is supplied as a powder and solvent for injectable solution (500 IU, 1,000 IU, 2,000 IU, or 3,000 IU of powder in a vial and 4 mL of solvent in a pre-filled syringe, plunger, and vial adapter – pack size 1).
• The powder is white to off-white and the solvent is clear and colourless.

Marketing Authorisation Holder and Manufacturer
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd, Denmark
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.
Instructions for using Refixia
Please read these instructions carefully before using Refixia.
Refixia is supplied as a powder. Before injection, a solution must be prepared (reconstitution) using the solvent provided in the syringe. The solvent is a histidine solution. The reconstituted solution must be injected intravenously (intravenous injection). The materials included in this pack are designed for reconstituting and injecting Refixia.
You will also need an infusion set (tubing and butterfly needle), sterile alcohol swabs, gauze, and adhesive bandages. These are not included in the Refixia pack.
Do not use the materials without adequate training from your doctor or nurse.
Always wash your hands and ensure the area around you is clean.
When preparing and injecting a medicine directly into a vein, it is important to use an aseptic and germ-free technique. Incorrect technique may introduce germs that could infect the bloodstream.
Do not open the materials until you are ready to use them.
Do not use the materials if they have been dropped or are damaged. Instead, use a new pack.
Do not use the materials if they are past the expiry date. Instead, use a new pack. The expiry date is printed on the outer carton, vial, vial adapter, and pre-filled syringe.
Do not use the materials if you suspect contamination. Instead, use a new pack.
Do not discard any of the components until after you have injected the reconstituted solution.
The materials are for single use only.
Contents
The pack contains:

• 1 vial with Refixia powder
• 1 vial adapter
• 1 pre-filled syringe with solvent
• 1 plunger (placed under the syringe)

General description

Pre-filled syringe with solvent
Plunger
Syringe tip
(under cap)
Syringe scale
Syringe cap

Plunger Threaded Wide End
1. Prepare the vial and syringe • Take out the number of Refixia packs you need. • Check the expiration date. • Check the name, dosage, and color of the packaging to ensure it contains the correct product. • Wash your hands and dry them thoroughly with a clean towel or hand dryer. • Remove the vial, vial adapter, and pre-filled syringe from the packaging. Leave the plunger inside the packaging. • Bring the vial and pre-filled syringe to room temperature. You can do this by holding them in your hands until they feel as warm as your hands. • Do not use other methods to warm the vial and pre-filled syringe.	A
Remove the plastic cap from the vial. If the plastic cap is loose or missing, do not use the vial. • Clean the rubber stopper of the vial with a sterile alcohol swab and let it air dry for a few seconds before use to ensure it is germ-free. • Do not touch the rubber stopper with your fingers, as you may transfer germs.	B
2. Attach the vial adapter • Remove the protective seal from the vial adapter. If the protective seal is not tightly closed or is broken, do not use the adapter. Do not remove the adapter from the protective cap with your fingers. If you touch the tip of the vial adapter, germs from your fingers may be transferred.	C
Place the vial on a flat, stable surface. • Twist the protective cap to attach the adapter onto the vial. Once attached, do not remove the adapter from the vial.	D
Gently press the protective cap with your thumb and index finger as shown. Remove the protective cap from the vial adapter. Do not lift the adapter from the vial when removing the protective cap.	E
3. Attach the plunger and syringe • Take the plunger by the wide end and remove it from the packaging. Do not touch any parts or the threads of the plunger. If you do, germs from your fingers may be transferred. • Immediately attach the plunger to the syringe by screwing it clockwise into the plunger rod inside the pre-filled syringe until you feel resistance.	F
Remove the syringe cap from the pre-filled syringe by bending it downward until it breaks. • Do not touch the tip of the syringe under the syringe cap. If you do, germs from your fingers may be transferred. If the syringe cap is loose or missing, do not use the pre-filled syringe.	G
Carefully screw the pre-filled syringe onto the adapter until you feel resistance.	H
4. Reconstitute the powder with the solvent • Hold the pre-filled syringe slightly tilted with the vial pointing downward. • Push the plunger to inject all the solvent into the vial.	I
Keep the plunger fully depressed and gently rotate the vial until the powder dissolves. Do not shake the vial to avoid foam formation. • Check the reconstituted solution. It should be clear and colorless or slightly yellow, with no visible particles. If you notice particles or color changes, do not use it. Instead, use a new pack.	J
Refixia must be used immediately after reconstitution. If not used, the medicine may no longer be sterile and could cause infections. If you cannot use the reconstituted Refixia solution immediately, it must be used within 4 hours if stored at room temperature (up to 30 °C) and within 24 hours if stored in the refrigerator (2 °C - 8 °C). Store the reconstituted medicine in the vial. Do not freeze the reconstituted Refixia solution or store it in the syringe.
Keep the reconstituted Refixia solution protected from light. If your dose requires more than one vial, repeat steps A to J with additional vials, adapters, and pre-filled syringes until the required dose is reached.
Keep the plunger fully depressed. • Rotate the syringe with the vial pointing downward. • Stop pushing the plunger and let it return on its own as the reconstituted solution fills the syringe. • Gently pull back the plunger to draw the reconstituted solution into the syringe. • If you need only part of the full dose, use the scale on the syringe to determine how much reconstituted solution to administer, according to instructions provided by your doctor or nurse. If there is air in the syringe at this point, inject the air into the vial. • With the vial held downward, gently tap the syringe to move any air bubbles upward. • Slowly push the plunger until all air bubbles have been expelled.	K
Unscrew the adapter with the vial. • Do not touch the tip of the syringe. If you do, germs from your fingers may be transferred.	L
5. Inject the reconstituted solution Refixia is now ready to be injected intravenously. • Administer the reconstituted solution according to your doctor's or nurse's instructions. • Inject slowly over 1–3 minutes. • Do not mix Refixia with other intravenous solutions or with other medicines. Inject Refixia through needle-free connectors for central venous catheters. Warning: The pre-filled syringe is made of glass and is designed to be compatible with standard luer-lock connectors. Some needle-free connectors with an internal tip are not compatible with
the pre-filled syringes. This incompatibility may prevent administration of the medicine and/or damage the needle-free connector. Inject the solution through a central venous access system (CVC), such as a central venous catheter or implanted port: • Use an aseptic, germ-free technique. Follow instructions for correct use of the connector and central venous catheter (CVC) as advised by your doctor or nurse. • Injection into a CVC may require the use of a sterile 10 mL plastic syringe to withdraw the reconstituted solution. This step should be performed after step J. • If the CVC line needs to be flushed before and after injection with Refixia, use an injectable sodium chloride 9 mg/mL solution.
Disposal • After injection, dispose of all unused Refixia solution, the syringe with infusion set, the vial with adapter, and other waste materials as instructed by your pharmacist. Do not dispose of them with household waste.	M
Do not dismantle the materials before disposal. Do not reuse the materials.