REFACTO AF 2000 IU POWDER AND SOLVENT FOR INJECTABLE SOLUTION IN PRE-FILLED SYRINGE

Introduction

Package Leaflet: Information for the User

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

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

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

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

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

moroctocog alfa (recombinant human coagulation factor VIII)

Read all of this 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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

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

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

ReFacto AF contains the active substance moroctocog alfa, human coagulation factor VIII. Factor VIII is necessary for blood to clot and stop bleeding. In patients with haemophilia A (congenital factor VIII deficiency), it is either not present or does not work properly.

ReFacto AF is used to treat and prevent (prophylaxis) bleeding episodes in adults and children of all ages (including newborns) with haemophilia A.

2. What you need to know before you use ReFacto AF

Do not use ReFacto AF

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

Talk to your doctor if you are unsure.

Warnings and precautions

Talk to your doctor or pharmacist before starting ReFacto AF

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

• the formation of inhibitors (antibodies) is a known complication that can occur during treatment with all factor VIII medicines. These inhibitors, especially at high levels, 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 being controlled with ReFacto AF, consult your doctor immediately.

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

Other medicines and ReFacto AF

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy, breast-feeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines

ReFacto AF has no influence on the ability to drive and use machines.

ReFacto AF contains sodium

After reconstitution, ReFacto AF contains 1.27 mmol (or 29 mg) of sodium (a major component of cooking/table salt) per pre-filled syringe. This is equivalent to 1.5% of the maximum recommended daily intake of sodium 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 consideration if you are on a low-salt diet.

3. How to use ReFacto AF

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are unsure, consult your doctor or pharmacist again.

Treatment with ReFacto AF should be started by a doctor experienced in the treatment of patients with haemophilia A. Your doctor will decide the dose of ReFacto AF you should receive. This dose and its duration will depend on your individual needs for factor VIII replacement therapy. ReFacto AF is given by injection into a vein and the injection takes several minutes. Injections of ReFacto AF can be given by the patients or by their caregivers, provided they have received appropriate training.

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

Consult your doctor before travelling. When you travel, you should carry your factor VIII product in sufficient quantity for the planned treatment.

It is recommended that each time you administer ReFacto AF, you record the name on the label and the batch number of the product. You can stick one of the detachable labels found on the pre-filled syringe to document the batch number in your diary or to report any side effects.

Reconstitution and administration

The following instructions are a guide for the reconstitution and administration of ReFacto AF supplied in a pre-filled syringe. Patients should follow the specific reconstitution and administration instructions given by their doctors.

ReFacto AF is administered by intravenous (IV) infusion after reconstitution. The pre-filled syringe is made up of two chambers, one chamber contains the lyophilized ReFacto AF powder and the other chamber contains the solvent [sodium chloride 9 mg/ml (0.9%) solution]. 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 pack. 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 pre-filled syringe must be reconstituted according to the specific instructions. To withdraw the reconstituted contents from each pre-filled syringe, a 10 ml syringe or a larger syringe with a luer lock (not included in this kit) may be used (refer to Additional Instructions).

Preparation

1. Always wash your hands before performing the following procedures.
2. During the reconstitution procedure, aseptic technique (i.e., clean and germ-free) must be followed.
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 pack.

Reconstitution

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

During the reconstitution process, it is important to keep the ReFacto AF pre-filled syringe in a vertical position (with the white powder on top of the clear solution) to prevent possible leaks.

1. Holding the pre-filled syringe in a vertical position, remove the white security seal by folding the seal from left to right (or by a careful rocking motion) to break the perforation of the stopper and expose the grey rubber stopper of the ReFacto AF pre-filled syringe.

1. Remove the blue sterile vent cap from its package.

While holding the ReFacto AF pre-filled syringe in a vertical position, remove the grey rubber stopper and replace it with the blue vent cap. This vent cap has small holes that allow air to escape to prevent a pressure increase. Avoid touching the open end of the pre-filled syringe or the blue vent cap.

1. Push the plunger slowly and carefullyuntil the two plungers of the pre-filled syringe meet, and all the solvent is transferred to the upper chamber containing the ReFacto AF powder.

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

1. With the ReFacto AF pre-filled syringe in a vertical position, shake it carefullyseveral times until the powder is dissolved.

Inspect the final solution visually for particulate matter or discoloration. The solution should have a transparent to slightly opalescent appearance and be colourless. Discard the pre-filled syringe if particles or discoloration are observed.

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

ReFacto AF must be used within 3 hours after reconstitution or after the grey stopper has been removed from the pre-filled syringe.

If you are not going to use the ReFacto AF solution immediately, you should store the pre-filled syringe in a vertical position, with the blue vent cap on the pre-filled syringe until you are ready for infusion. The reconstituted solution can be stored at room temperature for up to 3 hours. If you have not used it within 3 hours, discard it.

Administration (Intravenous Infusion)

Your doctor or another healthcare professional will teach you how to perform the infusion of ReFacto AF. Once you have learned how to perform self-infusion, you can 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). Once reconstituted and before administration, ReFacto AF must be inspected visually for particulate matter or discoloration.

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

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

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

1. Remove the protective cap from the needle and insert the butterfly needle of the infusion system into the vein, following the instructions of your doctor or another healthcare professional. The reconstituted product should be injected intravenously over several minutes. Your doctor may change the recommended infusion rate to make it more comfortable. Talk to your doctor or another healthcare professional about the infusion procedure. Do not perform self-infusion unless you are properly trained.

Reconstituted ReFacto AF must not be administered in the same tube or container with other medicines.

1. After infusion of ReFacto AF, remove the infusion system and discard it. The amount of medicine left in the infusion system does not affect your treatment.

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

It is recommended to record the batch number found on the label of the ReFacto AF pre-filled syringe each time you use ReFacto AF. You can use the detachable label from the ReFacto AF pre-filled syringe to record the batch number.

Additional Instructions:

Reconstituting multiple ReFacto AF pre-filled syringes to a 10 ml syringe or a larger syringe with a luer lock (10 ml syringes or luer lock syringes are not provided in the kit).

The following instructions are for the use of multiple ReFacto AF pre-filled syringe kits with a 10 ml syringe or a larger syringe with a luer lock.

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

Hold the ReFacto AF pre-filled syringe in a vertical position, slowly push the plunger until almost, but not all, the air has been eliminated from the chamber where the product is located.

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

1. Connect a sterile 10 ml syringe or a larger syringe with a luer lock to the open port of the connector and the ReFacto AF pre-filled syringe to the 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 the larger syringe with a luer lock.

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

1. Remove the luer-to-luer syringe connector from the 10 ml syringe or the larger syringe with a luer lock and attach the infusion system, as described above in the instructions for administration of the pre-filled syringe [see Administration (Intravenous Infusion)].

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

If you use more ReFacto AF than you should

Talk to your doctor or pharmacist.

If you stop using ReFacto AF

Do not stop using ReFacto AF without consulting your doctor.

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

4. Possible Adverse Effects

Like all medicines, this medicine may cause adverse effects, although not all people suffer from them.

Allergic Reactions

If allergic reactions(anaphylactic) sudden, severeappear, the infusion must be stopped immediately. You should consult your doctor immediatelyif you present any of the following early symptoms of allergic reactions:

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

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

Development of Inhibitors

In children who have not received previous treatment with medicines composed of factor VIII, inhibitory antibodies (see section 2) may occur very frequently (more than 1 in 10 patients); however, in patients who have received previous treatment with factor VIII (more than 150 days of treatment), the risk is rare (less than 1 in 100 patients). If this happens, the medicines you or your child take may stop working properly and you or your child may suffer from persistent bleeding. In that case, contact your doctor immediately.

Very Common Adverse Effects(may affect more than 1 in 10 patients)

• development of inhibitors in patients who had never been treated previously 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

• urticaria, skin rash, itching

• muscle pain
• chills, reaction related to the catheter site
• 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 who had been treated previously with factor VIII products (less than 1 in 100 patients)
• severe allergic reaction
• numbness, drowsiness, alteration of taste
• chest pain, rapid heartbeats, palpitations
• low blood pressure, pain and redness of the veins related to the presence of blood clots, flushing
• difficulty breathing
• excessive sweating
• weakness, reaction at the injection site (including pain)
• mild increase in cardiac enzymes
• increase in liver enzymes, increase in bilirubin

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing 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 expiration date that appears on the outer packaging and on the label of the pre-filled syringe after CAD. The expiration date is the last day of the month indicated.

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

For your convenience, the medicine can be removed from storage and stored at room temperature (up to 25°C) for a single period of 3 months maximum. At the end of this room temperature storage period, the product must not be refrigerated again, but must be used or discarded. Note on the outer packaging the date on which ReFacto AF in pre-filled syringe is removed from the refrigerator and placed at room temperature (up to 25°C). Keep the pre-filled syringe inside the outer packaging to protect it from light.

The reconstituted product must be used within 3 hours of reconstitution or removal of the gray cap.

The solution will be clear to slightly opalescent and colorless. Do not use this medicine if you notice that it is turbid or contains visible particles.

Medicines should not be thrown away through wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of ReFacto AF

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

• 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 injection solution 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).

Appearance of the Product and Package Contents

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

The package contents are:

• a pre-filled syringe containing 250, 500, 1000, 2000, or 3000 IU of moroctocog alfa powder and 4 ml of sterile sodium chloride 9 mg/ml (0.9%) solution for injection for reconstitution
• a plunger
• a sterile protective cap for ventilation
• a sterile infusion system
• two alcohol swabs
• adhesive tape
• a gauze

Marketing Authorization Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Brussels

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

You can request more information about this medicine by contacting the local representative of the marketing authorization holder.

Date of Last Revision of this Prospectus: 02/2025.

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