Refacto AF 3000 IU powder and solvent for solution for injection in pre-filled syringe

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

ReFacto AF 250 IU powder and solvent for solution for injection in pre-filled syringe

ReFacto AF 500 IU powder and solvent for solution for injection in pre-filled syringe

ReFacto AF 1000 IU powder and solvent for solution for injection in pre-filled syringe

ReFacto AF 2000 IU powder and solvent for solution for injection in pre-filled syringe

ReFacto AF 3000 IU powder and solvent for solution for injection in pre-filled syringe

moroctocog alfa (recombinant human coagulation factor VIII)

Read the entire leaflet carefully before you start 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 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 reactions, consult your doctor or pharmacist, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet:

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

1. What ReFacto AF is and what it is used for

ReFacto AF contains the active substance moroctocog alfa, human coagulation factor VIII. Factor VIII is necessary for blood to form clots and stop bleeding. In patients with haemophilia A (an inherited factor VIII deficiency), factor VIII is either missing or does not function properly.

ReFacto AF is used for the treatment and prevention (prophylaxis) of bleeding episodes in adults and children of all ages (including newborns) with haemophilia A.

2. What you need to know before using ReFacto AF

Do not use ReFacto AF

• if you are allergic to moroctocog alfa or to any of the other components of this medicine (listed in section 6);
• if you are allergic to hamster proteins.

Consult your doctor if you have any doubts.

Warnings and precautions

Talk to your doctor or pharmacist before starting to use ReFacto AF

• if you experience allergic reactions. Some signs of allergic reactions include difficulty breathing, shortness of breath, swelling, hives, itching, chest tightness, wheezing, and low blood pressure. Anaphylaxis is a serious allergic reaction causing difficulty swallowing or breathing, redness or swelling of the hands, face, or both. If any of these symptoms occur, stop the infusion immediately and contact your doctor or seek immediate emergency medical help. In cases of severe allergic reactions, alternative treatment should be considered.

• the development of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII-containing medicines. These inhibitors, especially at high levels, may prevent the treatment from working properly, so you or your child will be closely monitored for the development of such inhibitors. If your bleeding or your child's bleeding is not controlled with ReFacto AF, contact your doctor immediately.

• if your bleeding does not stop as expected, contact your doctor or seek immediate emergency medical help.

Other medicines and ReFacto AF

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

Pregnancy, breastfeeding and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and use of machines

ReFacto AF has no influence on the ability to drive or operate machinery.

ReFacto AF contains sodium

After reconstitution, ReFacto AF contains 1.27 mmol (or 29 mg) of sodium (main component of table/cooking salt) per pre-filled syringe. This corresponds to 1.5% of the maximum recommended daily sodium intake for an adult. Depending on your body weight and your dose of ReFacto AF, you may receive multiple pre-filled syringes. This should be taken into account if you are on a low-salt diet.

3. How to use ReFacto AF

Follow exactly the administration instructions for this medicine given by your doctor. If in doubt, consult your doctor or pharmacist again.

Treatment with ReFacto AF should be initiated by a physician experienced in the treatment of patients with haemophilia A. Your doctor will determine the dose of ReFacto AF you should receive. This dose and its duration will depend on your individual requirements for factor VIII replacement therapy. ReFacto AF is administered by intravenous injection, which takes several minutes. Injections of ReFacto AF may be given by patients or their caregivers, provided they have received appropriate training.

During your treatment, your doctor may adjust the dose of ReFacto AF you receive.

Consult your doctor before travelling. When travelling, you should carry a sufficient supply of your factor VIII product for the intended treatment.

It is recommended that each time ReFacto AF is administered, you record the name shown on the packaging and the product's batch number. You may affix one of the peel-off labels from the pre-filled syringe to document the batch number in your diary or to report any adverse reactions.

Reconstitution and Administration

The instructions provided below are a guide for the reconstitution and administration of ReFacto AF supplied in a pre-filled syringe. Patients must follow the specific reconstitution and administration instructions provided by their physicians.

ReFacto AF is administered by intravenous (IV) infusion after reconstitution. The pre-filled syringe consists of two chambers: one chamber contains the lyophilised ReFacto AF powder, and the other chamber contains the solvent [sodium chloride solution 9 mg/mL (0.9%)]. Throughout these instructions, this device will be referred to as the pre-filled syringe.

For reconstitution, use only the pre-filled syringe provided in the package. For administration, other sterile disposable syringes may be used.

ReFacto AF must not be mixed with other infusion solutions.

Note: If you need to use more than one pre-filled syringe of ReFacto AF per infusion, each syringe must be reconstituted according to the specific instructions. To withdraw the reconstituted contents from each syringe, a 10 mL syringe or a larger syringe with a luer lock (not included in this kit) may be used (see Additional Instructions).

Preparation

1. Always wash your hands before performing the following procedures.
2. An aseptic technique (i.e., clean and germ-free) must be maintained during the reconstitution procedure.
3. To minimize exposure to air, all components used in the reconstitution and administration of this product should be used as soon as possible after opening the sterile packaging.

Reconstitution

1. Allow the pre-filled syringe to reach room temperature.
2. Remove the components of the ReFacto AF pre-filled syringe kit and place them on a clean surface, ensuring you have all the materials you will need.
3. Hold the plunger as shown in the diagram. Firmly screw the plunger into the opening of the ReFacto AF pre-filled syringe, pushing and twisting clockwise until resistance is felt (approximately 2 turns).

During the reconstitution process, it is important to keep the ReFacto AF pre-filled syringe in an upright position (with the white powder above the clear solution) to prevent possible leakage.

1. Holding the pre-filled syringe upright, remove the white safety seal by bending it from left to right (or with a careful rocking motion) to break the perforation of the cap and expose the grey rubber stopper of the ReFacto AF pre-filled syringe.

1. Remove the sterile blue venting cap from its packaging.

While holding the ReFacto AF pre-filled syringe upright, remove the grey rubber stopper and replace it with the blue protective venting cap. This venting cap has small openings that allow air to escape, preventing pressure build-up. Avoid touching the open end of the syringe or the blue protective venting cap.

1. Push the plunger slowly and carefully until both plungers of the pre-filled syringe meet and all the solvent is transferred into the upper chamber containing the ReFacto AF powder.

Note: To prevent fluid leakage from the syringe tip, do not push the plunger with excessive force.

1. With the ReFacto AF pre-filled syringe in an upright position, gently agitate it several times until the powder is completely dissolved.

Visually inspect the final solution for particles or discoloration. The solution should appear transparent to slightly opalescent and colourless. Discard the pre-filled syringe if particles or discoloration are observed.

1. Continuing with the ReFacto AF pre-filled syringe in an upright position, advance the plunger until almost, but not all, of the air has been removed from the (upper) chamber.

ReFacto AF must be used within 3 hours after reconstitution or after removal of the grey rubber stopper from the pre-filled syringe.

If you do not use the ReFacto AF solution immediately, store the syringe upright with the blue protective venting cap attached to the pre-filled syringe until ready for infusion. The reconstituted solution may be stored at room temperature for up to 3 hours. If not used within 3 hours, discard it.

Administration (Intravenous Infusion)

Your doctor or another healthcare professional will teach you how to perform the ReFacto AF infusion. Once you have learned how to perform self-infusion, you may follow the instructions included in this leaflet.

ReFacto AF is administered by intravenous (IV) infusion after reconstitution of the powder with the solvent (0.9% sodium chloride). After reconstitution and before administration, ReFacto AF must be visually inspected for particles or discoloration.

ReFacto AF should be administered using the infusion set provided in this kit, unless your doctor or another healthcare professional has given you different instructions.

1. Remove the blue protective venting cap and firmly attach the infusion device to the ReFacto AF pre-filled syringe.

1. Apply a tourniquet and prepare the injection site by thoroughly cleaning the skin with one of the alcohol swabs provided.

1. Remove the protective cap from the needle and insert the butterfly needle of the infusion set into the vein, following your doctor’s or healthcare professional’s instructions. The reconstituted product should be injected intravenously over several minutes. Your doctor may adjust the recommended infusion rate for your comfort. Discuss the infusion procedure with your doctor or healthcare professional. Do not perform self-infusion unless you are properly trained.

Reconstituted ReFacto AF must not be administered in the same tubing or container with other medications.

1. After infusion of ReFacto AF, remove and discard the infusion set. The amount of medication remaining in the infusion set does not affect your treatment.

Note: Dispose of unused solution, the empty pre-filled syringe, and used medical materials in an appropriate container for medical waste, as these materials may harm others if not properly discarded.

It is recommended to record the batch number shown on the label of the ReFacto AF pre-filled syringe each time you use ReFacto AF. You may use the peel-off label from the ReFacto AF pre-filled syringe to document the batch number.

Additional Instructions:

Multiple reconstitution of ReFacto AF from pre-filled syringes into a 10 mL syringe or a larger syringe with luer lock (10 mL syringes or luer lock syringes are not provided in the kit).

The following instructions are for using multiple ReFacto AF pre-filled syringe kits with a 10 mL syringe or a larger syringe with luer lock.

1. Reconstitute all ReFacto AF pre-filled syringes following the instructions above (see Reconstitution and Administration).

Hold the ReFacto AF pre-filled syringe upright and slowly push the plunger until almost, but not all, of the air has been expelled from the chamber containing the product.

1. Remove the luer-to-luer syringe connector from its packaging (luer-to-luer syringe connectors are not included).

2. Connect a sterile 10 mL syringe or a larger luer lock syringe to one open port of the syringe connector, and connect the ReFacto AF pre-filled syringe to the remaining open port on the opposite side.

1. With the ReFacto AF pre-filled syringe on top, slowly push the plunger until the contents are emptied into the 10 mL syringe or larger luer lock syringe.

1. Remove the ReFacto AF pre-filled syringe and repeat steps 3 and 4 for additional reconstituted syringes.

2. Remove the luer-to-luer syringe connector from the 10 mL syringe or larger luer lock syringe and attach the infusion set as described above in the administration instructions for the pre-filled syringe [see Administration (Intravenous Infusion)].

Note: Dispose of unused solution, the empty pre-filled syringe, and used medical materials in an appropriate container for medical waste, as these materials may harm others if not properly discarded.

If you use more ReFacto AF than you should

Consult your doctor or pharmacist.

If you stop treatment with ReFacto AF

Do not stop using ReFacto AF 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 reactions

If sudden, severe allergic (anaphylactic) reactions occur, the infusion must be stopped immediately. You should consult your doctor immediately if you experience any of the following early symptoms of allergic reactions:

• rash, urticarial wheals, hives, generalized itching
• swelling of lips and tongue
• difficulty breathing, wheezing, chest tightness
• general feeling of malaise
• dizziness and loss of consciousness

Severe symptoms such as difficulty breathing and fainting (or near-fainting) require immediate emergency treatment. Sudden, severe allergic (anaphylactic) reactions are uncommon (may affect up to 1 in 100 patients).

Development of inhibitors

In children who have not previously received treatment with factor VIII-containing medicines, inhibitory antibodies may develop very frequently (more than 1 in 10 patients); however, in patients who have previously received factor VIII treatment (more than 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). If this occurs, the medicines you or your child are taking may no longer work properly, and you or your child may experience persistent bleeding. In such a case, contact your doctor immediately.

Very common adverse effects (may affect more than 1 in 10 patients)

• development of inhibitors in patients who have never previously been treated with factor VIII products
• headache
• cough
• joint pain
• fever

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

• bleeding
• dizziness
• loss of appetite, diarrhea, vomiting, stomach pain, nausea
• hives, skin rash, itching
• muscle pain
• chills, catheter site-related reaction
• some blood tests may show an increase in antibodies against factor VIII

Uncommon adverse effects (may affect up to 1 in 100 patients)

• development of inhibitors in patients previously treated with factor VIII products (less than 1 in 100 patients)
• severe allergic reaction
• numbness, drowsiness, taste disturbances
• chest pain, rapid heartbeat, palpitations
• low blood pressure, pain and redness of veins related to presence of blood clots, flushing
• difficulty breathing
• excessive sweating
• weakness, injection site reaction (including pain)
• slight increase in cardiac enzymes
• increase in liver enzymes, increase in bilirubin

Reporting of adverse effects

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

5. Storage of ReFacto AF

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 prefilled syringe after EXP. The expiry date refers to the last day of the month indicated.

Store and transport refrigerated (between 2°C and 8°C). Do not freeze, to avoid damaging the prefilled syringe.

For convenience, the medicine may be removed from refrigeration and stored at room temperature (up to 25°C) for a single period of up to 3 months. After this period at room temperature, the product must not be returned to refrigerated storage, but should either be used or discarded. Record on the outer packaging the date when the ReFacto AF prefilled syringe is removed from the refrigerator and placed at room temperature (up to 25°C). Keep the prefilled syringe inside the outer packaging to protect it from light.

The reconstituted product should be used within 3 hours after reconstitution or removal of the grey stopper.

The solution should be clear to slightly opalescent and colourless. Do not use this medicine if it appears cloudy or contains visible particles.

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

6. Contents of the pack and other information

Composition of ReFacto AF

• The active substance is moroctocog alfa (recombinant coagulation factor VIII). Each pre-filled syringe of ReFacto AF contains nominally 250, 500, 1000, 2000 or 3000 IU of moroctocog alfa.

For reconstitution of moroctocog alfa, a solvent [sodium chloride injectable solution 9 mg/ml (0.9%)] is included in the pre-filled syringe of ReFacto AF.

• The other components are sucrose, calcium chloride dihydrate, L-histidine, polysorbate 80 and sodium chloride (see section 2 “ReFacto AF contains sodium”).

• After reconstitution with the solvent [sodium chloride solution 9 mg/ml (0.9%)], the prepared solution for injection contains 62.5, 125, 250, 500 or 750 IU of moroctocog alfa per ml, respectively (depending on the potency of moroctocog alfa, i.e., 250, 500, 1000, 2000 or 3000 IU).

Nature and contents of the container

ReFacto AF is a pre-filled syringe with powder and solvent for injectable solution, containing ReFacto AF powder in the upper chamber and solvent [sodium chloride injectable solution 9 mg/ml (0.9%)] in the lower chamber.

The pack contents are:

• one pre-filled syringe containing 250, 500, 1000, 2000 or 3000 IU of moroctocog alfa powder and 4 ml of sterile solvent, sodium chloride 9 mg/ml (0.9%) solution for injection, for reconstitution
• one plunger
• one sterile venting cap
• one sterile infusion system
• two alcohol wipes
• adhesive plaster
• one gauze pad

Marketing Authorisation Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Manufacturer

Wyeth Farma, S.A.

Autovía del Norte A-1 Km 23

Desvío Algete Km 1

28700 San Sebastián de los Reyes

Madrid

Spain

More information on this medicine is available upon request by contacting the local representative of the Marketing Authorisation Holder.

Date of the most recent review of this leaflet: 02/2025.

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