Label: information for the user

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

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

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

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

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

moroctocog alfa (human recombinant coagulation factor VIII)

Read this label carefully before starting to use this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only for you and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist even if they are not listed in this label. See section 4.

1.What is ReFacto AF and how is it used

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

3.How to use ReFacto AF

4.Possible adverse effects

5.Storage of ReFacto AF

6.Contents of the package and additional information

ReFacto AF contains the active ingredient moroctocog alfa, human coagulation factor VIII. Factor VIII is necessary for blood to form clots and stop bleeding. In patients with hemophilia A (congenital factor VIII deficiency), it is either absent 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 hemophilia A.

No use ReFacto AF

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

Consult your doctor if you have any doubts.

Warnings and precautions

Consult 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 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 immediate medical assistance. In cases of severe allergic reactions, alternative treatment should be considered.

• The formation of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII medications. 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 these 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 immediate medical assistance..

Other medications and ReFacto AF

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

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 medication

Driving and operating machinery

The influence of ReFacto AF on the ability to drive and operate machinery is none.

ReFacto AF contains sodium.

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

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor or pharmacist again.

The treatment with ReFacto AF should be initiated by a doctor with experience in treating patients with hemophilia A. Your doctor will decide the dose of ReFacto AF that you should receive. This dose and its duration will depend on your individual needs for factor VIII substitution treatment. ReFacto AF is administered by injection into a vein and this injection takes several minutes. ReFacto AF injections can be administered by patients or their caregivers, provided they have received proper training.

Your doctor may modify the dose of ReFacto AF that you receive during your treatment.

Consult your doctor before traveling. When traveling, you should carry enough factor VIII product for the planned treatment.

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

Reconstitution and Administration

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

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

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

ReFacto AF should not be mixed with other infusion solutions.

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

Preparation

1. Wash your hands before performing the following procedures.
2. During the reconstitution procedure, follow aseptic technique (i.e., clean and germ-free).
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 package.

Reconstitution

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

During the reconstitution process, it is essential to maintain 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. Hold the pre-filled syringe in a vertical position, carefully break the safety seal by folding the seal from left to right (or by a gentle 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 sterile blue ventilation stopper 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 ventilation stopper. This ventilation stopper has small holes that allow air to escape to prevent pressure increase. Avoid touching the open end of the syringe or the blue ventilation stopper.

1. Push the plungerslowly and carefullyuntil the two plungers of the pre-filled syringe collide, and all the diluent is transferred to the upper chamber containing the ReFacto AF powder.

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

1. With the ReFacto AF pre-filled syringe in a vertical position, gently agitate several times until the powder dissolves.

Visually inspect the final solution for the presence of particles or discoloration. The solution should have a transparent to slightly opalescent appearance and will be colorless. 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 removed from the upper chamber (superior).

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

If you are not going to use the ReFacto AF solution immediately, store the syringe in a vertical position, with the blue ventilation stopper in 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 do not use it within 3 hours, discard it.

Administration (Intravenous Infusion)

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

ReFacto AF is administered by intravenous infusion (IV) after reconstitution of the powder with the diluent (sodium chloride 0.9%). Once reconstituted and before administration, ReFacto AF should be visually inspected for the presence of particles 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 other instructions.

1. Remove the blue ventilation stopper 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 wipes 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 product reconstituted should be infused intravenously over several minutes. Your doctor may change the recommended infusion rate to make it more comfortable. Discuss the infusion procedure with your doctor or another healthcare professional. Do not perform self-infusion unless you have been properly trained.

ReFacto AF reconstituted should not be administered in the same tube or container with other medications.

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

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

It is recommended that you 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 on the ReFacto AF pre-filled syringe to record the batch number.

Additional Instructions:

Multiple Reconstitution of ReFacto AF in Pre-filled Syringe to a 10cc Syringe or a Larger Syringe with Luer Lock (10cc or Luer Lock Syringes are not provided in the kit).

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

1. Reconstitute all the 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 removed from the chamber where the product is located.

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

1. Connect a sterile 10cc syringe or a larger syringe with 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 at the top, slowly push the plunger until the contents are emptied into the 10cc syringe or the larger syringe with luer lock.

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

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

Note: Discard the unused solution, the pre-filled syringe, and medical materials used 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

Consult your doctor or pharmacist.

If you interrupt treatment with ReFacto AF

Do not stop usingReFacto AF without consulting your doctor.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, this medicine may cause side effects, although not everyone will experience them

Allergic reactions

If you experiencesudden, severe allergic reactions (anaphylaxis),stop the infusion immediatelyand consult your doctor immediately if you experience any of the following early symptoms of allergic reactions:

• hives, urticarial rash, widespread itching
• swelling of the 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 immediate emergency treatment. Sudden, severe allergic reactions (anaphylaxis) are rare (may affect up to 1 in 100 patients)

Development of inhibitors

In children who have not received prior treatment with factor VIII-containing medications, inhibitors (see section 2) may develop very frequently (more than 1 in 10 patients); however, in patients who have received prior treatment with factor VIII (more than 150 days of treatment), the risk is rare (less than 1 in 100 patients). If this occurs, the medications you or your child take may not work properly and you or your child may experience persistent bleeding. In this case, contact your doctor immediately.

Very common side 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 side 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, reaction related to the catheter location
• some blood tests may show an increase in antibodies against factor VIII

Rare side 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, altered taste
• chest pain, rapid heartbeats, palpitations
• low blood pressure, pain and redness of veins related to the presence of blood clots, flushing
• difficulty breathing
• excessive sweating
• weakness, reaction at the injection site (including pain)
• slight increase in cardiac enzymes
• increase in liver enzymes, increase in bilirubin

Reporting of side effects

If you experienceany type of side effect, consult your doctor or pharmacist, even if it is apossibleside effect not listed in this leaflet.You can also report them directly to theSpanish System for Pharmacovigilance of Medicinal Products for Human Use:www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the outer packaging and on the pre-filled syringe label 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 medication can be removed from storage and stored at room temperature (up to 25ºC) for a maximum period of 3 months. At the end of this storage period at room temperature, the product should not be refrigerated again, but rather used or discarded. Note on the outer packaging the date when ReFacto AF in pre-filled syringe is removed from the refrigerator and placed at room temperature (up to 25ºC). 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 grey stopper.

The solution will be clear to slightly opalescent and colorless. Do not use this medication if it appears turbid or contains visible particles.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. In this way, you will help protect the environment.

Composition of ReFacto AF

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

For the reconstitution of moroctocog alfa, a solvent [injectable sodium chloride solutionof9mg/ml (0.9%)] is included in the pre-filled syringe of ReFacto AF.

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

-After reconstitution with the solvent [sodium chloride solutionof9mg/ml (0.9%)], the prepared injection solution contains 62.5, 125, 250, 500 or 750UI of moroctocog alfa per ml, respectively (according to the potency of moroctocog alfa, i.e. 250, 500, 1000, 2000 or 3000UI).

Appearance of the product and contents of the package

ReFacto AF is a pre-filled syringe with powder and solvent for injection solution that contains the powder of ReFacto AF in the upper chamber and the solvent[injectable sodium chloride solutionof9mg/ml (0.9%)] in the lower chamber.

The contents of the package are:

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

Marketing Authorization Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050Brussels

Belgium

Responsible for manufacturing

Wyeth Farma, S.A.

Autovía del Norte A-1 Km23

Algete Km 1 exit

28700 San Sebastián de los Reyes

Madrid

Spain

For more information about this medicine, please contact the local representative of the marketing authorization holder.

Spain

Pfizer, S.L.

Phone: +34 91 490 99 00

Last review date of this leaflet: 09/2021

For detailed information about this medicine, please visit the website of the European Medicines Agency:http://www.ema.europa.eu/.