Refixia 2000 IU powder and solvent for solution for injection: detailed information

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Refixia 500UI powder and solvent for solution for injection

Refixia 1000UI powder and solvent for solution for injection

Refixia 2000UI powder and solvent for solution for injection

Refixia 3000UI powder and solvent for solution for injection

nonacog beta pegol

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Section 4 includes information on how to report side effects.

Read the entire leaflet carefully before you start using this medicine, as 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.
This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
If you experience any side effects, consult your doctor, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

What Refixia is and what it is used for
What you need to know before using Refixia
How to use Refixia
Possible side effects
How to store Refixia
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 nonacog beta pegol. It is a long-acting 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 to treat and prevent bleeding episodes in patients of all age groups with haemophilia B (congenital factor IX deficiency).

In patients with haemophilia B, factor IX is either missing or does not work properly. Refixia replaces this missing or malfunctioning factor IX and helps the blood 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 components of this medicine (listed in section 6).
if you are allergic to hamster proteins.

If you are in any of the above situations or are unsure about them, consult your doctor before using this medicine.

Warnings and precautions

Traceability

It is important to keep a record of the batch number of Refixia. Therefore, each time you receive a new pack of Refixia, you should note down the date and the batch number (shown on the packaging after "Batch") and keep this information in a safe place.

Allergic reactions and development of inhibitors

There is a minimal risk that a sudden and severe allergic reaction (e.g., an anaphylactic reaction) may occur with Refixia. Stop the infusion and contact your doctor or emergency services immediately if you experience signs of an allergic reaction, such as rash, hives, urticaria, widespread itching, redness and/or swelling of the lips, tongue, face or hands, difficulty swallowing or breathing, shortness of breath, wheezing, chest tightness, pale and cold skin, palpitations and/or dizziness.

Your doctor may need to treat these reactions promptly. Your doctor may also perform a blood test to check whether you have developed factor IX inhibitors (neutralizing antibodies) against your medicine, as inhibitors may develop alongside allergic reactions. If you develop such inhibitors, you may have an increased risk of experiencing sudden and severe allergic reactions (e.g., anaphylactic reactions) during future treatment with factor IX.

Due to the risk of allergic reactions with factor IX, your initial treatment with Refixia should be carried out in a healthcare facility or under the supervision of a healthcare professional who can provide appropriate medical care in case of allergic reactions.

Contact your doctor immediately if bleeding does not stop as expected or if you need to significantly increase the amount of Refixia required 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 higher in individuals who have not previously been treated with factor IX-containing medicines, usually young children.

Blood clots

Inform your doctor if any of the following apply to you, as the risk of blood clot formation increases during treatment with Refixia:

you have recently undergone surgery
you have another serious illness, such as liver disease, heart disease, or cancer
you have risk factors for developing heart disease, such as high blood pressure, obesity, or smoking.

Kidney disease (nephrotic syndrome)

There is a minimal risk of developing a specific kidney disease called "nephrotic syndrome" after administration of high doses of factor IX in patients with hemophilia B and factor IX inhibitors, as well as in those with a history of allergic reactions.

Catheter-related complications

If you have a central venous access device (CVAD), you may develop infections or blood clots at the catheter insertion site.

Other medicines and Refixia

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using Refixia.

Driving and using machines

Refixia has no influence on 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 case of treatment with multiple vials, the total sodium content should be taken into consideration.

3. How to use Refixia

A doctor experienced in treating patients with haemophilia B will initiate treatment with Refixia. Follow exactly the instructions for administration of this medicine given by your doctor. If in doubt, consult your doctor again on how to use Refixia.

Your doctor will calculate your appropriate dose based on your body weight and the intended use of the medicine.

Prevention of bleeding

The usual dose of Refixia is 40 international units (IU) per kg of body weight. It is administered by injection once a week. Your doctor may choose a different dose or change the frequency of injections according to your needs.

Treatment of bleeding

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. Consult your doctor for the appropriate dose and number of injections needed.

Use in children and adolescents

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

How Refixia is administered

Refixia is available as a powder and solvent to prepare a solution (reconstitution) which must be injected into a vein. See "Instructions for using Refixia" for more information.

If you use more Refixia than you should

If you use more Refixia than you should, contact your doctor.

If you need to significantly increase the amount of Refixia required to stop a bleed, inform your doctor immediately. For more information, see section 2 "Allergic reactions and development of inhibitors".

If you forget to use Refixia

If you miss a dose, inject the missed dose as soon as you remember. Do not administer a double dose to compensate for the missed dose. If you have any doubts, contact your doctor.

If you stop using Refixia

If you stop treatment with Refixia, you will no longer be protected against bleeding, or an existing bleed may not stop. Do not stop treatment with Refixia without first discussing it with your doctor.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions may occur with this medicine.

If sudden and severe allergic reactions (e.g., anaphylactic reactions) occur, the injection must be stopped immediately. If you experience any of the following early symptoms 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
rash, hives, welts, or itching
pale and cold skin, palpitations, and/or dizziness (low blood pressure).

In previously untreated children receiving factor IX medications, the development of inhibitors (see section 2) is common (up to 1 in 10 patients). If this occurs, the medication may no longer work properly and your child may experience persistent bleeding. If this happens, you must contact your doctor immediately.

The following side effects have been observed with Refixia:

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

allergic reactions (hypersensitivity). These may become severe and could be life-threatening (anaphylactic reactions)
itching (pruritus)
skin reactions at the injection site
nausea
feeling very tired
rash
in previously untreated children receiving factor IX medications: neutralizing antibodies (inhibitors), anaphylactic reactions.

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

palpitations
hot flushes.

Reporting of side effects

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

5. Storage of Refixia

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

Do not use Refixia after the expiry date stated on the packaging and on the labels of the vial and the pre-filled syringe, following “EXP”. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze. Keep the vial in its outer packaging to protect it 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 was removed from the refrigerator and placed at room temperature. The new expiry date must never extend beyond the one stated on the carton. Dispose of this medicine if it has not been used before the new expiry date. Once stored at room temperature, do not return the medicine to the refrigerator.

Use the injection immediately after preparing the solution (reconstitution). If immediate use is not possible, the solution must be used within 24 hours if stored in a refrigerator between 2 °C and 8 °C, or within 4 hours if stored outside the refrigerator at a maximum temperature of 30 °C.

The powder in the vial is a white to off-white powder. Do not use if the colour of the powder has changed.

The reconstituted solution is clear and colourless to slightly yellow. Do not use the reconstituted solution if it contains particles or shows signs of discolouration.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Doing so helps protect the environment.

6. Package contents and other information

Composition of Refixia

The active substance is nonacog beta pegol (pegylated recombinant human coagulation factor IX). Each Refixia vial contains 500 IU, 1,000 IU, 2,000 IU, or 3,000 IU of nonacog beta pegol, 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.

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, one plunger rod with a vial adapter; pack size of 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

Date of the most recent revision of this leaflet:

Other sources of information

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

Instructions for using Refixia

Read these instructions carefully before using Refixia.

Refixia is supplied as a powder. Before injection, a solution (reconstituted) must be prepared using the solvent provided in the syringe. The solvent is a histidine solution. The reconstituted solution should be injected into a vein (intravenous [IV] injection). The components in this package are designed to reconstitute and inject Refixia.

You will also need an intravenous infusion set (tubing and butterfly needle), sterile alcohol wipes, gauze, and bandages. These materials are not included in the Refixia package.

Do not use the equipment without proper training from your doctor or nurse.

Always wash your hands and ensure the area around you is clean.

When preparing and injecting medication directly into veins, it is important to use a clean, germ-free (aseptic) technique. Incorrect technique may introduce germs capable of causing blood infections.

Do not open the equipment until you are ready to use it.

Do not use the equipment if it has been dropped or damaged. Use a new package instead.

Do not use the equipment if it has expired. Use a new package instead. The expiration date is printed on the outer packaging, vial, vial adapter, and pre-filled syringe.

Do not use the equipment if you suspect contamination. Use a new package instead.

Do not discard any components until the reconstituted solution has been injected.

The equipment is for single use only.

Contents

The package contains:

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

Diagram of a Refixia vial showing the plastic cap and underlying rubber stopper on a white background

Diagram of a vial adapter with protective cover, protruding spike under the protective cap, and protective cap on a blue background

Diagram of a pre-filled syringe showing parts: tip, cap, graduated scale, and plunger on a white background

Diagram of a syringe showing parts: Luer lock connector

Prepare the vial and syringe

Prepare the number of Refixia packages you need.

Check the expiration date.

Verify the name, concentration, and color of the package to confirm it contains the correct product.

Wash your hands thoroughly and dry them properly with a clean towel or air dry.

Remove the vial, vial adapter, and pre-filled syringe from the package. Leave the plunger rod untouched inside the package.

Allow the vial and pre-filled syringe to reach room temperature. You can do this by holding both in your hands until they feel the same temperature as your hands.

Do not use any other method to warm the vial and pre-filled syringe.

Two hands holding a drug vial and a vial respectively on a blue background with the letter A in the upper left corner

Remove the plastic cap from the vial. If the plastic cap is loose or missing, do not use the vial.

Clean the rubber stopper with a sterile alcohol wipe and allow it to air dry for a few seconds before use to ensure it is as germ-free as possible.

Do not touch the rubber stopper with your fingers, as this may transfer germs.

A hand grasping a small glass vial with a blue arrow pointing toward it

Attach the vial adapter

Remove the protective paper from the vial adapter.

If the protective paper is not fully sealed or is torn, do not use the vial adapter.

Do not remove the vial adapter from its protective cover with your fingers. If you touch the spike of the vial adapter, you may transfer germs from your fingers.

Two hands lifting a transparent lid off a medical container with a blue arrow pointing upward

Place the vial on a flat, hard surface.

Turn the protective cover upside down and press the vial adapter firmly onto the vial.

Once attached, do not remove the vial adapter from the vial.

A hand pressing a protective cap downward onto a small glass vial to seal or open it, with a blue arrow pointing downward

Gently squeeze the protective cover between your thumb and index finger as shown.

Remove the protective cover from the vial adapter.

Do not remove the vial adapter from the vial when removing the protective cover.

A hand lifting a protective cap vertically off a medicine vial with a blue arrow pointing upward

Assemble the plunger rod and syringe

Hold the plunger rod by the wide end and remove it from the package. Do not touch the sides or threads of the plunger rod. Touching them may transfer germs from your fingers.

Immediately connect the plunger rod to the syringe by turning it clockwise into the plunger inside the pre-filled syringe until resistance is felt.

Two gloved hands holding a syringe with a curved arrow indicating clockwise rotation of the barrel for drug preparation

Remove the cap from the pre-filled syringe by bending it downward until the perforation breaks.

Do not touch the tip of the syringe below the syringe cap. Touching it may transfer germs from your fingers.

If the syringe cap is loose or missing, do not use the pre-filled syringe.

Two hands separating a protective cap from an injection pen following the direction indicated by a curved blue arrow

Screw the pre-filled syringe firmly onto the vial adapter until resistance is felt.

Two hands holding a cylindrical medical device and rotating it clockwise as indicated by a curved blue arrow on a blue background

Reconstitute the powder with the solvent

Hold the pre-filled syringe at a slight angle with the vial pointing downward.

Press the plunger rod to inject all the solvent into the vial.

A hand holding a tilted syringe with a blue arrow indicating downward pressure movement of the plunger

Keep the plunger rod fully depressed and gently swirl the vial until the powder is completely dissolved.

Do not shake the vial, as this may cause foaming.

Inspect the reconstituted solution. It should be clear and colorless to slightly yellow with no visible particles. If particles or discoloration are observed, do not use it. Use a new package instead.

A hand holding a syringe vertically to insert it into a glass vial while a circular arrow indicates a rotational movement

It is recommended to use Refixia immediately after reconstitution, as delaying use may compromise sterility and lead to infections.

If the reconstituted Refixia solution cannot be used immediately, it must be used within 4 hours if stored at room temperature (up to 30°C) or within 24 hours if refrigerated (between 2°C and 8°C). Store the reconstituted product in the vial.

Do not freeze the reconstituted Refixia solution or store it in syringes.

Store the reconstituted Refixia solution away from direct light.

If your dose requires more than one vial, repeat steps A through J with additional vials, vial adapters, and pre-filled syringes until the required dose is achieved.

Keep the plunger rod fully depressed.

Turn the syringe with the vial upside down.

Stop pushing the plunger rod and allow it to retract on its own as the reconstituted solution fills the syringe.

Gently pull the plunger rod downward to draw the reconstituted solution into the syringe.

If only part of the vial is needed, use the syringe scale to measure the amount of reconstituted solution withdrawn, as instructed by your doctor or nurse.

If air is present in the syringe at any point, inject the air back into the vial.

While holding the vial upside down, gently tap the syringe to allow any bubbles to rise to the top.

Slowly push the plunger rod until all bubbles are expelled.

A hand holding a syringe vertically and pressing the plunger downward, indicated by a blue arrow, to draw liquid from the vial

Unscrew the vial adapter from the vial.

Do not touch the tip of the syringe. Touching it may transfer germs from your fingers.

Two hands holding a cylindrical medical device while the right hand rotates the terminal end clockwise as indicated by a curved arrow

Inject the reconstituted solution

Refixia is now ready to be injected into a vein.

Inject the reconstituted solution following your doctor’s or nurse’s instructions.
Inject slowly over 1 to 3 minutes.
Do not mix Refixia with any other infusion solution or intravenous medication.

Injecting Refixia through needle-free connectors for intravenous (IV) catheters

Caution: The pre-filled syringe is made of glass and is designed to be compatible with standard luer-lock connections. Some needle-free connectors with an internal spike are incompatible with the pre-filled syringe. This incompatibility may prevent drug administration and/or damage the needle-free connector.

Injecting the solution through a central venous access device (CVAD), such as a central venous catheter or subcutaneous port:

Use a clean, germ-free (aseptic) technique. Follow instructions for proper use of your connector and CVAD as advised by your doctor or nurse.
Injection via a CVAD may require using a sterile 10 ml plastic syringe to withdraw the reconstituted solution. This should be done immediately after step J.
If flushing the CVAD line is required before or after injecting Refixia, use a 9 mg/ml sodium chloride solution for injection.

Disposal

After injection, safely dispose of all unused Refixia solution, the syringe with infusion set, the vial with vial adapter, and other waste according to your pharmacist’s instructions.

Do not throw it in household trash.

Medical diagram showing an injection pen, a vial, and a needle being inserted into the top of a circular device with radial lines

Do not disassemble the equipment before disposal.

Do not reuse the equipment.