Refacto AF

Package leaflet: Information for the user

ReFacto AF 250 IU powder and solvent for solution for injection, 500 IU powder and solvent for solution for injection, 1000 IU powder and solvent for solution for injection, 2000 IU powder and solvent for solution for injection

moroctocog alfa (recombinant human coagulation factor VIII)
Please 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 questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this 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 to stop bleeding. In patients with haemophilia A (congenital factor VIII deficiency), factor VIII is missing or does not work properly.
ReFacto AF is used for the treatment and prevention of bleeding episodes (prophylaxis) in adults and children of all ages (including neonates) with haemophilia A.

2. What you should know before using ReFacto AF

Do not use ReFacto AF

• if you are allergic to moroctocog alfa 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 about this, consult your doctor.
Warnings and precautions
Talk to your doctor or pharmacist before using 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 that may cause difficulty swallowing and/or breathing, flushing or swelling of the face and/or hands. If any of these symptoms occur, stop the infusion immediately and contact a doctor or go immediately to the emergency room. In case of severe allergic reactions, alternative therapy should be considered.

• inhibitor (antibody) formation 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, and you or your child will be closely monitored for the development of such inhibitors. If ReFacto AF does not control bleeding as expected, inform your doctor immediately.

• if bleeding does not stop as expected, contact your doctor or go immediately to the emergency room.

Other medicines and ReFacto AF
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before using this medicine.
Driving and using machines
ReFacto AF does not affect the ability to drive or operate machinery.
ReFacto AF contains sodium
After reconstitution, ReFacto AF contains 1.27 mmol (or 29 mg) of sodium (a main component of table salt) in each vial. This corresponds to 1.5% of the maximum daily recommended dietary intake for an adult. Depending on your body weight and your dose of ReFacto AF, you may receive more than one vial. This should be taken into account if you are on a low-sodium diet.

3. How to use ReFacto AF

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Treatment with ReFacto AF should be initiated by a physician experienced in the management of patients with haemophilia A. Your doctor will determine the dose of ReFacto AF you will receive. This dose and 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 themselves or by their caregivers, provided they have been adequately trained.
During treatment, your doctor may decide to adjust the dose of ReFacto AF you are taking.
Consult your doctor before travelling. You should carry an adequate supply of factor VIII product for your anticipated treatment needs while travelling.
It is recommended to record the name on the outer packaging and the batch number of the product each time you use ReFacto AF. You may use one of the removable labels found on the vial to track the batch number in your diary or to report any adverse effects.

Reconstitution and Administration
The instructions below provide general guidance for the reconstitution and administration of ReFacto AF. Patients must follow the specific reconstitution and administration procedures provided by their doctor.
For reconstitution, use only the pre-filled syringe supplied in the pack. For administration, other sterile disposable syringes may be used.
ReFacto AF is administered by intravenous (iv) infusion after reconstitution of the lyophilised powder for injection using the solvent syringe supplied [sodium chloride solution 9 mg/ml (0.9%)]. ReFacto AF must not be mixed with other infusion solutions.
Always wash your hands before performing the following reconstitution and administration procedures.
During the reconstitution procedure, use an aseptic technique (i.e., work under clean and germ-free conditions).

Reconstitution

1. Allow the vial of lyophilised ReFacto AF and the pre-filled solvent syringe to reach room temperature.
2. Remove the plastic cap from the ReFacto AF vial to expose the central portion of the rubber stopper.

3. Wipe the top of the vial with the alcohol swab provided, or use another disinfectant and allow it to dry. After cleaning, do not touch the rubber stopper with your hands and do not allow it to contact any surface.
4. Remove the lid from the plastic transparent packaging of the adapter. Do not remove the adapter from its packaging.
5. Place the vial on a flat surface. Holding the adapter packaging, position the adapter on top of the vial. Press firmly downward on the packaging until the adapter snaps into the top of the vial and the tip of the adapter pierces the vial stopper.

6. Remove the packaging from the adapter and discard it.

7. Attach the plunger to the solvent syringe by inserting the plunger into the seal opening of the syringe and pressing and rotating it firmly until it locks securely into the stopper.
8. Remove the plastic safety cap from the end of the solvent syringe by breaking it at the perforation. This is done by bending the cap back and forth until the perforation breaks. Do not touch the inside of the cap or the end of the syringe. The cap may need to be replaced (if the reconstituted ReFacto AF is not administered immediately); therefore, replace it by placing it on its top surface.

9. Place the vial on a flat surface. Connect the solvent syringe to the vial adapter by inserting the syringe tip into the adapter opening and pressing and rotating the syringe firmly clockwise until it locks into place.

10. Slowly press the plunger to inject all the solvent into the ReFacto AF vial.

11. While keeping the syringe attached to the adapter, gently rotate the vial until the powder is completely dissolved.

12. The final solution should be inspected visually for particulate matter before administration. The solution should appear clear to slightly opalescent and colourless.

Note: If more than one vial of ReFacto AF is used for infusion, each vial must be reconstituted according to the instructions above. The solvent syringe should be removed, leaving the vial adapter in place, and a single large luer-lock syringe may be used to withdraw the reconstituted contents from each vial.

13. Ensuring that the syringe plunger is still fully depressed, invert the vial. Slowly draw all the solution into the syringe through the vial adapter.

14. Disconnect the syringe from the vial adapter by gently pulling and rotating it counterclockwise. Discard the vial with the attached adapter.

Note: If the solution is not used immediately, the syringe cap should be carefully replaced. Do not touch the syringe tip or the inside of the cap.
ReFacto AF must be used within 3 hours after reconstitution. The reconstituted solution may be stored at room temperature prior to administration.

Administration (Intravenous Infusion)
ReFacto AF should be administered using the infusion set supplied in this kit and the pre-filled solvent syringe provided, or a single sterile disposable plastic luer-lock syringe.

1. Connect the syringe to the luer end of the infusion set tubing.
2. Apply a compression bandage and prepare the injection site by cleaning the skin thoroughly with the alcohol swab provided in the kit.

3. Insert the needle of the infusion set tubing into a vein as instructed by your doctor, and remove the compression bandage. Remove any air present in the infusion set tubing by aspirating into the syringe. The reconstituted product should be injected intravenously over several minutes. Your doctor may adjust the recommended infusion rate to make the infusion more comfortable.

Dispose of unused solution, empty vials, used syringes, and needles in an appropriate container for medical waste, as these materials can cause harm to others if not disposed of properly.

If you use more ReFacto AF than you should
Contact your doctor or pharmacist.

If you stop treatment with ReFacto AF
Do not stop treatment with ReFacto AF without first consulting your doctor.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Allergic reactions
If severe, sudden allergic reactions (anaphylactic) occur, the infusion must be stopped immediately.
Contact your doctor immediately if you experience any of the following initial symptoms of
allergic reactions:

• skin rash, hives, wheals, generalized itching
• swelling of the lips and tongue
• difficulty breathing, shortness of breath, chest tightness
• general feeling of illness
• dizziness and loss of consciousness

Severe symptoms, including difficulty breathing and (sensation of) fainting, require immediate
emergency treatment. Severe, sudden allergic reactions (anaphylactic) are not common (affecting up to
1 in 100 people).
Development of inhibitors
For children who have not previously been treated with factor VIII-containing medicines, the formation
of inhibitory antibodies (see section 2) can be very common (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, your or your child’s medicines may stop
working properly and you or your child may experience persistent bleeding. If this happens, you must
contact your doctor immediately.
Very common side effects (affect more than 1 in 10 people)

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

Common side effects (affect up to 1 in 10 people)

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

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

• development of inhibitors in patients previously treated with factor VIII-containing products (in fewer than 1 in 100 people)
• severe allergic reaction
• numbness, drowsiness, altered taste
• chest pain, increased heart rate, palpitations
• low blood pressure, pain and redness in veins associated with a blood clot, hot flushes
• shortness of breath
• excessive sweating
• weakness, reactions at the injection site including pain
• slight increase in cardiac enzymes
• increase in liver enzymes, increase in bilirubin

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or
pharmacist. You can also report side effects directly via the national reporting system detailed in
Annex V. By reporting side effects, you can help provide more information on the safety of this
medicine.

5. How to store ReFacto AF

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and on the label of the
vial after Exp. The expiry date refers to the last day of that month.
Store and transport in a refrigerator at a temperature between 2°C and 8°C. Do not freeze, in order to
avoid damage to the pre-filled solvent syringe.
For your convenience, the medicine may be removed from refrigeration for a single period of up to 3
months at room temperature (up to 25°C). After this period of storage at room temperature, the medicine
must not be returned to the refrigerator, but must either be used or discarded. Record on the packaging
the date when ReFacto AF was removed from the refrigerator and stored at room temperature (up to
25°C). Keep the vial in its packaging to protect it from light.
Use the reconstituted solution within 3 hours after reconstitution.
The solution should be clear to slightly opalescent and colourless. Do not use this medicine if you notice
that it is cloudy or contains visible particles.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose
of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ReFacto AF contains

• The active substance is moroctocog alfa (recombinant coagulation factor VIII). Each vial of ReFacto AF nominally contains 250, 500, 1000, or 2000 IU of moroctocog alfa.
• The other components are sucrose, calcium chloride dihydrate, L-histidine, polysorbate 80, and sodium chloride (see section 2 “ReFacto AF contains sodium”). A solvent is also provided [sodium chloride injection solution 9 mg/ml (0.9%)] for reconstitution.
• After reconstitution with the provided solvent [sodium chloride solution 9 mg/ml (0.9%)], each vial contains respectively 62.5, 125, 250, or 500 IU of moroctocog alfa (according to the moroctocog alfa dosage of 250, 500, 1000, or 2000 IU) per 1 ml of the resulting injectable solution.

Description of the appearance of ReFacto AF and contents of the pack
ReFacto AF is supplied as a powder for injectable solution in a glass vial, together with a pre-filled syringe containing the solvent.
The packs contain:

• one vial of powder containing 250, 500, 1000, or 2000 IU of moroctocog alfa
• one pre-filled syringe with 4 ml of sterile sodium chloride injection solution 9 mg/ml (0.9%) for reconstitution, with a plunger
• one sterile vial adapter for reconstitution
• one sterile infusion set
• two alcohol swabs
• one adhesive plaster
• one gauze pad

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer
Wyeth Farma S.A
Autovia del Norte A-1 Km 23
Desvio Algete Km 1
28700 San Sebastian de los Reyes
Madrid
Spain

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Luxembourg/Luxemburg Pfizer Luxembourg SARL filialas Lietuvoje
Pfizer NV/SA Tel: +370 5 251 4000
Tél/Tel: +32 (0)2 554 62 11

България Magyarország
Пфайзер Люксембург САРЛ, Клон Pfizer Kft.
България Tel.: +36 1 488 37 00
Тел.: +359 2 970 4333

Česká republika Malta
Pfizer, spol. s r.o. Vivian Corporation Ltd.
Tel: +420 283 004 111 Tel: +356 21344610

Danmark Nederland
Pfizer ApS Pfizer bv
Tlf: +45 44 20 11 00 Tel: +31 (0)800 63 34 636

Deutschland Österreich
PFIZER PHARMA GmbH Pfizer Corporation Austria Ges.m.b.H.
Tel: +49 (0)30 550055-51000 Tel: +43 (0)1 521 15-0

Eesti Polska
Pfizer Luxembourg SARL Eesti filiaal Pfizer Polska Sp. z o.o.
Tel: +372 666 7500 Tel.: +48 22 335 61 00

Ελλάδα Portugal
Pfizer Ελλάς Α.Ε. Laboratórios Pfizer, Lda.
Τηλ: +30 210 6785800 Tel: +351 21 423 5500

España România
Pfizer S.L. Pfizer Romania S.R.L.
Tel: +34 91 490 99 00 Tel: +40 (0) 21 207 28 00

France Slovenija
Pfizer Pfizer Luxembourg SARL,
Tél: +33 (0)1 58 07 34 40 podružnica za svetovanje s področja farmacevtske dejavnosti, Ljubljana
Tel: +386 (0)1 52 11 400

Hrvatska Slovenská republika
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL, organizačná zložka
Tel: +385 1 3908 777 Tel: +421 2 3355 5500

Ireland Suomi/Finland
Pfizer Healthcare Ireland Pfizer Oy
Tel: 1800 633 363 (toll free) Puh/Tel: +358 (0)9 430 040
Tel: +44 (0)1304 616161

Ísland Sverige
Icepharma hf. Pfizer AB
Sími: +354 540 8000 Tel: +46 (0)8 550 520 00

Italia United Kingdom (Northern Ireland)
Pfizer S.r.l. Pfizer Limited
Tel: +39 06 33 18 21 Tel: +44 (0)1304 616161

Κύπρος
Pfizer Ελλάς Α.Ε. (Cyprus Branch)
Τηλ: +357 22817690

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel: +371 670 35 775

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/.

Instructions for the user: package leaflet

Instructions for the user: package leaflet

ReFacto AF 250 IU powder and solvent for injectable solution in pre-filled syringe, 500 IU powder and solvent for injectable solution in pre-filled syringe, 1000 IU powder and solvent for injectable solution in pre-filled syringe, 2000 IU powder and solvent for injectable solution in pre-filled syringe, 3000 IU powder and solvent for injectable solution in pre-filled syringe

moroctocog alfa (recombinant human coagulation factor VIII)
Please read 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, consult your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any adverse reaction, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this 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 to stop bleeding. In patients with haemophilia A (congenital factor VIII deficiency), factor VIII is missing or does not function properly.
ReFacto AF is used for the treatment and prevention of bleeding episodes (prophylaxis) in adults and children of all ages (including neonates) with haemophilia A.

2. What you should know before using ReFacto AF

Do not use ReFacto AF

• if you are allergic to moroctocog alfa 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 about this, consult your doctor.
Warnings and precautions
Talk to your doctor or pharmacist before using ReFacto AF

• if you experience allergic reactions. Some signs of allergic reactions include difficulty breathing, shortness of breath, swelling, hives, itching, tightness in the chest, wheezing, and
  low blood pressure. Anaphylaxis is a serious allergic reaction that may cause difficulty
  swallowing and/or breathing, redness or swelling of the face and/or hands. If any of these
  symptoms occur, stop the infusion immediately and contact a doctor or go immediately to the emergency room. In case of severe allergic reactions, alternative therapy should be considered.

• inhibitor (antibody) formation is a known complication that may occur during treatment with all factor VIII medicines. These inhibitors, especially at high levels, may prevent the treatment from working properly, and you or your child will be closely monitored for the development of such inhibitors. If ReFacto AF does not control bleeding as expected, inform your doctor immediately.

• if bleeding does not stop as expected, contact your doctor or go immediately to the emergency room.

Other medicines and ReFacto AF
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or are breastfeeding, ask your doctor or pharmacist for advice before using this medicine.
Driving and using machines
ReFacto AF does not affect the ability to drive or operate machinery.
ReFacto AF contains sodium
After reconstitution, ReFacto AF contains 1.27 mmol (or 29 mg) of sodium (the main component of table salt) in each pre-filled syringe. This corresponds to 1.5% of the maximum recommended daily dietary intake for an adult. Depending on your body weight and your dose of ReFacto AF, you may receive more than one pre-filled syringe. This should be taken into account if you are on a low-sodium diet.

3. How to use ReFacto AF

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Treatment with ReFacto AF should be initiated by a doctor experienced in managing patients with haemophilia A. Your doctor will determine the dose of ReFacto AF you will receive. This dose and duration will depend on your individual requirements for factor VIII replacement therapy. ReFacto AF is administered by intravenous injection, which lasts several minutes. Injections of ReFacto AF may be given by patients themselves or by their caregivers, provided they have been adequately trained.
During treatment, your doctor may decide to adjust the dose of ReFacto AF you are taking.
Consult your doctor before travelling. You should carry a sufficient supply of factor VIII product for your anticipated treatment needs while travelling.
It is recommended to record the name on the outer packaging and the batch number of the product each time you use ReFacto AF. You may use one of the removable labels on the pre-filled syringe to track the batch number in your diary or to report any adverse reactions.

Reconstitution and Administration
The procedures described below are guidelines for reconstituting and administering ReFacto AF supplied in a pre-filled syringe. Patients must follow the specific reconstitution and administration procedures provided by their doctor.
ReFacto AF is administered by intravenous (IV) infusion after reconstitution. The pre-filled syringe consists of two chambers: one chamber contains the lyophilized powder of ReFacto AF and the other contains the solvent [sodium chloride solution 9 mg/ml (0.9%)]. In the following instructions, the device will be referred to as the pre-filled syringe.
For reconstitution, use only the pre-filled syringe provided in the box. 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 for infusion, each syringe must be reconstituted according to the specific instructions. An additional 10 ml or larger luer-lock syringe (not included in this kit) may be used to withdraw the reconstituted solution from each syringe (see Additional Instructions).

Preparation

1. Always wash your hands before performing the following procedures.
2. During the reconstitution procedure, use an aseptic technique (i.e., work under clean, germ-free conditions).
3. All components used during reconstitution and administration of the product should be used as soon as possible after opening their sterile containers to minimize unintended exposure to air.

Reconstitution

1. Allow the pre-filled syringe to reach room temperature.
2. Remove the contents of the ReFacto AF pre-filled syringe kit and place them on a clean surface, ensuring you have everything you need.
3. Grasp the plunger as shown in the figure below. Firmly screw the plunger into the opening of the ReFacto AF pre-filled syringe by pushing and turning clockwise until resistance is felt (approximately 2 turns).

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

4. While holding the ReFacto AF pre-filled syringe in an upright position, remove the white anti-tamper seal by bending it from right to left (or with a gentle rocking motion) to break the perforation on the cap and expose the grey rubber cap covering the tip of the pre-filled syringe.

5. Remove the sterile blue perforated protective cap from its packaging.
   While continuing to hold the ReFacto AF pre-filled syringe in an upright position, remove the grey rubber cap covering the tip and replace it with the blue perforated protective cap. The perforated cap has tiny holes that allow air to escape, preventing pressure build-up. Avoid touching the open end of the syringe or the blue perforated protective cap.

6. Gently and slowly push the plunger until the two pistons inside the pre-filled syringe meet and all the solvent has been transferred into the upper chamber containing the ReFacto AF powder.

Note: To prevent liquid from leaking out of the syringe tip, do not push the plunger too forcefully.

7. With the ReFacto AF pre-filled syringe still in an upright position, gently swirl in small circular motions several times until the powder is completely dissolved.

Inspect the final solution for visible particles or unusual discoloration. The solution should be clear or slightly opalescent and colorless. Discard the pre-filled syringe if you notice visible particles or abnormal coloration.

8. While continuing to hold the ReFacto AF pre-filled syringe in an upright position, slowly push the plunger until most, but not all, of the air is expelled from the (upper) chamber.

ReFacto AF must be infused within 3 hours after reconstitution or after removal of the grey cap covering the tip of the pre-filled syringe.
If you do not use the ReFacto AF solution immediately, store the syringe in an upright position with the blue perforated protective cap attached to the pre-filled syringe until you are ready for infusion. The reconstituted solution may be stored at room temperature for up to 3 hours. If not used within 3 hours, it must be discarded.

Administration (Intravenous Infusion)
Your doctor or nurse will teach you how to perform the ReFacto AF infusion. After learning how to perform self-infusion, you may follow the instructions contained in this Patient Information Leaflet.
ReFacto AF is administered by intravenous (IV) infusion after reconstituting the powder with the solvent (0.9% sodium chloride). After reconstitution and before administration, ReFacto AF must be inspected for visible particles or unusual discoloration.
ReFacto AF should be administered using the infusion kit provided in the kit, unless otherwise instructed by your doctor or nurse.

1. Remove the blue perforated protective cap and firmly attach the provided intravenous infusion kit to the ReFacto AF pre-filled syringe.

2. Apply a tourniquet and prepare the injection site by thoroughly wiping the skin with the alcohol swab provided in the kit.

3. Remove the needle protective cap and insert the butterfly needle at the end of the connector of the infusion kit into your vein, following the instructions provided by your doctor or nurse. Remove the tourniquet. The reconstituted ReFacto AF should be injected intravenously over several minutes. Your doctor may adjust the recommended infusion rate to make the infusion more comfortable. Discuss your intravenous infusion procedure with your doctor or nurse. Do not attempt self-infusion unless you have been properly trained.

Reconstituted ReFacto AF must not be administered through the same infusion line or in the same container as other medicines.

4. After infusing ReFacto AF, remove and discard the infusion kit. The amount of product remaining in the infusion kit does not affect your treatment.

Note: Dispose of all unused solution, the empty pre-filled syringe, and all other used kit components in a designated container for biological waste, as this material could injure others if not properly discarded.

It is recommended to record the batch number shown on the label of the ReFacto AF pre-filled syringe at each administration of ReFacto AF. You may use the adhesive label on the ReFacto AF pre-filled syringe to record the batch number.

Additional Instructions:
Transferring Reconstituted ReFacto AF from Multiple Pre-filled Syringes into a 10 ml or Larger Luer-Lock Syringe (10 ml or larger luer-lock syringes are not provided)
The following instructions will allow you to transfer the contents of multiple ReFacto AF pre-filled syringes into a single 10 ml or larger luer-lock syringe.

1. Reconstitute all ReFacto AF pre-filled syringes according to the reconstitution instructions described above (see Reconstitution and Administration).
   While holding the ReFacto AF pre-filled syringe in an upright position, slowly push the plunger until most, but not all, of the air is expelled from the chamber containing the product.

2. Remove the luer-to-luer syringe connector from its packaging (luer-to-luer connectors are not provided).
3. Connect a sterile 10 ml or larger luer-lock syringe to one end of the syringe connector and the ReFacto AF pre-filled syringe to the opposite end.

4. With the ReFacto AF pre-filled syringe positioned above, slowly push the plunger to completely empty its contents into the 10 ml or larger luer-lock syringe.

5. Remove the empty ReFacto AF pre-filled syringe and repeat steps 3 and 4 for any additional reconstituted syringes.
6. Remove the luer-to-luer syringe connector from the 10 ml or larger luer-lock syringe and attach the infusion kit as described above in the administration instructions for the pre-filled syringe [see Administration (Intravenous Infusion)].

Note: Dispose of all unused solution, the empty pre-filled syringe, and all other used kit components in a designated container for biological waste, as this material could injure others if not properly discarded.

If you use more ReFacto AF than you should
Contact your doctor or pharmacist.
If you stop treatment with ReFacto AF
Do not stop treatment with ReFacto AF without first consulting your doctor.
If you have any questions about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Allergic reactions
If severe, sudden allergic reactions (anaphylactic) occur, the injection must be stopped immediately.
Contact your doctor immediately if you experience any of the following initial symptoms of
allergic reactions:

• skin rash, hives, wheals, generalized itching
• swelling of the lips and tongue
• difficulty breathing, shortness of breath, chest tightness
• general feeling of illness
• dizziness and loss of consciousness

Severe symptoms, including difficulty breathing and (feeling of) fainting, require immediate
emergency treatment. Severe, sudden allergic reactions (anaphylactic) are not common
(affecting up to 1 in 100 people).
Development of inhibitors
For children who have not previously been treated with factor VIII-containing medicines, the
formation of inhibitory antibodies (see section 2) can be very common (more than 1 patient in 10);
however, in patients who have previously received treatment with factor VIII (more than 150 days of
treatment), the risk is uncommon (less than 1 patient in 100). If this occurs, your or your child's
medicines may stop working properly and you or your child may experience persistent bleeding.
If this happens, you must contact your doctor immediately.
Very common side effects (affect more than 1 in 10 people)

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

Common side effects (affect up to 1 in 10 people)

• bleeding
• dizziness
• loss of appetite, diarrhoea, vomiting, stomach pain, nausea
• hives, skin rash, itching
• muscle pain
• chills, reaction at the catheter site
• certain blood tests may show an increase in antibodies against factor VIII

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

• development of inhibitors in patients who have been previously treated with products containing factor VIII (in less than 1 person in 100)
• severe allergic reaction
• numbness, drowsiness, taste disturbances
• chest pain, rapid heartbeat, palpitations
• low blood pressure, pain and redness of veins associated with a blood clot, hot flushes
• shortness of breath
• excessive sweating
• weakness, injection site reactions including pain
• slight increase in cardiac enzymes
• increase in liver enzymes, increase in bilirubin

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or
pharmacist. You can also report side effects directly via the national reporting system detailed in
Annex V. By reporting side effects, you can help provide more information on the safety of this
medicine.

5. How to store 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 carton and on the label of the pre-filled syringe after "Exp". The expiry date refers to the last day of that month.
Store and transport in a refrigerator at a temperature between 2°C and 8°C. Do not freeze, to avoid damage to the pre-filled syringe.
For your convenience, the medicine may be removed from refrigeration for a single period of up to 3 months at room temperature (up to 25°C). After this period of storage at room temperature, the medicine must not be returned to the refrigerator, but must either be used or discarded. Please record on the packaging the date when the ReFacto AF pre-filled syringe was removed from the refrigerator and stored at room temperature (up to 25°C).
Keep the pre-filled syringe in its original packaging to protect it from light.
Use the reconstituted solution within 3 hours after reconstitution or after removal of the grey cap covering the tip.
The solution should be clear to slightly opalescent and colourless. Do not use this medicine if you notice that the solution is cloudy or contains visible particles.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What ReFacto AF contains

• The active substance is moroctocog alfa (recombinant coagulation factor VIII). Each pre-filled syringe of ReFacto AF nominally contains 250, 500, 1000, 2000, or 3000 IU of moroctocog alfa. A solvent [sodium chloride 9 mg/ml (0.9%) injection solution] is included in the ReFacto AF pre-filled syringe pack to reconstitute the moroctocog alfa.
• 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 provided solvent [sodium chloride 9 mg/ml (0.9%) solution], the prepared injection solution contains 62.5, 125, 250, 500, or 750 IU of moroctocog alfa per ml, respectively (depending on the moroctocog alfa dose, i.e., 250, 500, 1000, 2000, or 3000 IU).

Description of the appearance of ReFacto AF and contents of the pack
ReFacto AF is supplied as a powder and solvent for injection solution in a pre-filled syringe, with
the ReFacto AF powder in the upper chamber and the solvent [sodium chloride 9 mg/ml (0.9%)
solution] in the lower chamber.
The packs contain:

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

Marketing Authorisation Holder
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer
Wyeth Farma S.A
Autovia del Norte A-1 Km 23
Desvio Algete Km 1
28700 San Sebastian de los Reyes
Madrid
Spain

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Luxembourg/Luxemburg Pfizer Luxembourg SARL filialas Lietuvoje
Pfizer NV/SA Tel: +370 5 251 4000
Tél/Tel: +32 (0)2 554 62 11

България Magyarország
Пфайзер Люксембург САРЛ, Клон Pfizer Kft.
България Tel.: + 36 1 488 37 00
Тел.: +359 2 970 4333

Česká republika Malta
Pfizer, spol. s r.o. Vivian Corporation Ltd.
Tel: +420 283 004 111 Tel: +356 21344610

Danmark Nederland
Pfizer ApS Pfizer bv
Tlf: +45 44 20 11 00 Tel: +31 (0)800 63 34 636

Deutschland Norge
PFIZER PHARMA GmbH Pfizer AS
Tel: +49 (0)30 550055-51000 Tlf: +47 67 52 61 00

Eesti Österreich
Pfizer Luxembourg SARL Eesti filiaal Pfizer Corporation Austria Ges.m.b.H.
Tel: +372 666 7500 Tel: +43 (0)1 521 15-0

Ελλάδα Polska
Pfizer Ελλάς Α.Ε Pfizer Polska Sp. z o.o.
Τηλ: +30 210 6785800 Tel.: +48 22 335 61 00

España Portugal
Pfizer S.L. Laboratórios Pfizer, Lda.
Tel: +34 91 490 99 00 Tel: +351 21 423 5500

France România
Pfizer Pfizer Romania S.R.L.
Tél: +33 (0)1 58 07 34 40 Tel: +40 (0) 21 207 28 00

Hrvatska Slovenija
Pfizer Croatia d.o.o. Pfizer Luxembourg SARL
Tel: + 385 1 3908 777 Pfizer, podružnica za svetovanje s področja
farmacevtske dejavnosti, Ljubljana
Tel: + 386 (0) 1 52 11 400

Ireland Slovenská republika
Pfizer Healthcare Ireland Pfizer Luxembourg SARL, organizačná zložka
Tel: 1800 633 363 (toll free) Tel: + 421 2 3355 5500
Tel: +44 (0)1304 616161

Ísland Suomi/Finland
Icepharma hf. Pfizer Oy
Sími: +354 540 8000 Puh/Tel: +358 (0)9 430 040

Italia Sverige
Pfizer S.r.l. Pfizer AB
Tel: +39 06 33 18 21 Tel: + 46 (0)8 550 520 00

Κύπρος United Kingdom (Northern Ireland)
Pfizer Ελλάς Α.Ε. (Cyprus Branch) Pfizer Limited
Τηλ: +357 22817690 Tel: +44 (0)1304 616161

Latvija
Pfizer Luxembourg SARL filiāle Latvijā
Tel: +371 670 35 775

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu / .