Helixate NexGen 500 IU powder and solvent for solution forinjection

Helixate NexGen 500 IU contains the active substance human recombinant coagulation factor VIII (octocog alfa).

Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency).
This preparation does not contain von Willebrand factor and is therefore not to be used in von Willebrand's disease.

The vial with powder contains 500 IU (International Units) of octocog alfa. After reconstitution with the water for injection, each vial contains octocog alfa 200 IU/ml.

Do not use Helixate NexGen 500 IU

• If you are allergic (hypersensitive) to octocog alfa, or to any of the other ingredients of Helixate NexGen 500 IU ( see Section 6 and end of Section 2).
• If you are allergic to mouse or hamster protein. If you are unsure about this, ask your doctor.

Take special care with Helixate NexGen 500 IU

• If you experience tightness in the chest, feeling dizzy, feeling sick or faint, or experience dizziness on standing, you may be experiencing a rare severe sudden allergic reaction (a so-called anaphylactic reaction) to Helixate NexGen 500 IU. If this occurs, stop administering the product immediately and seek medical advice.
• Your doctor may carry out tests to ensure that your current dose of Helixate NexGen 500 IU provides adequate factor VIII levels.
• If your bleeding is not being controlled with your usual dose of Helixate NexGen, consult your doctor immediately. You may have developed factor VIII inhibitors and your doctor may carry out tests to confirm this. Factor VIII inhibitors are antibodies in the blood which block the factor VIII you are using, and makes it less effective to prevent and control bleeding.
• If you have previously developed a factor VIII inhibitor and you switch factor VIII products, you may be at risk of your inhibitor coming back.

Using other medicines
Interactions with other medicines are not known. However, please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding
Experience regarding the use of Helixate NexGen during pregnancy and breast-feeding is not available. Therefore, if you are pregnant or breast-feeding, consult your doctor before using this product.

Driving and using machines
No effects on ability to drive or use machines have been observed.

Important information about some of the ingredients of Helixate NexGen 500 IU This medicinal product contains less than 23 mg sodium per vial, i.e. essentially ?sodium-free?.

• Helixate NexGen 500 IU is intended for intravenous administration only and must be administered immediately after reconstitution.
• You must use aseptic conditions (meaning clean and germ free) during reconstitution and administration. Use only the medical devices for reconstitution and administration that are provided with each package of Helixate NexGen 500 IU.
• Helixate NexGen 500 IU must not be mixed with other infusion solutions. Do not use solutions containing visible particles or that are cloudy. Follow the directions given by your doctor closely and use the instructions below as a guide:

Reconstitution and administration

1. Wash your hands thoroughly using soap and warm water. 2. Warm both unopened vials in your hands to a comfortable temperature do not exceed 37 C. 3. Ensure product and solvent vial flip caps are removed and the stoppers are treated with an aseptic solution and allowed to dry prior to opening the Mix2Vial package. 4. Open the Mix2Vial package by peeling away the lid. Do not remove the Mix2Vial from the blister package 5. Place the solvent vial on an even, clean surface and hold the vial tight. Take the Mix2Vial together with the blister package and push the spike of the blue adapter end straight down through the solvent vial stopper. 6. Carefully remove the blister package from the Mix2Vial set by holding at the rim, and pulling vertically upwards. Make sure that you only pull away the blister package and not the Mix2Vial set. 7. Place the product vial on an even and firm surface. Invert the solvent vial with the Mix2Vial set attached and push the spike of the transparent adapter end straight down through the product vial stopper. The solvent will automatically flow into the product vial. 8. With one hand grasp the product-side of the Mix2Vial set and with the other hand grasp the solvent-side and unscrew the set carefully into two pieces. Discard the solvent vial with the blue Mix2Vial adapter attached. 9. Gently swirl the product vial with the transparent adapter attached until the substance is fully dissolved. Do not shake. 10. Draw air into an empty, sterile syringe. While the product vial is upright, connect the syringe to the Mix2Vials Luer Lock fitting. Inject air into the product vial. 11. While keeping the syringe plunger pressed, invert the system upside down and draw the solution into the syringe by pulling the plunger back slowly. 12. Now that the solution has been transferred into the syringe, firmly hold on to the barrel of the syringe keeping the syringe plunger facing down and disconnect the transparent Mix2Vial adapter from the syringe. Hold the syringe upright and push the plunger until no air is left in the syringe. 13. Apply a tourniquet. 14. Determine the point of injection and prepare antiseptically. 15. Puncture the vein and secure the venipuncture set with a plaster. 16 Let blood flow back to the open end of the venipuncture set and then attach the syringe with the solution. Make sure that no blood enters the syringe. 17. Remove tourniquet. 18. Inject the solution intravenously over several minutes, keeping an eye on the position of the needle. The speed of administration should be based on the patients comfort, but should not be faster than 2mlmin maximum rate of infusion. 19. If a further dose needs to be administered, use a new syringe with product reconstituted as described above. 8

20. If no further dose is required, remove the venipuncture set and syringe. Hold a swab firmly over the injection site on the outstretched arm for approx. 2 minutes. Finally, apply a small pressure dressing to the wound.

Treatment of bleeding

How much Helixate NexGen 500 IU you should use and how often you should use it depends on many factors such as your weight, the severity of your haemophilia, where the bleed is and how serious it is, whether you have inhibitors and how high the inhibitor titre is and the factor VIII level that is needed.

Your doctor will calculate the dose of Helixate NexGen 500 IU and how frequently you should use it to get the necessary level of factor VIII activity in your blood. He/she should always adjust the amount of Helixate NexGen 500 IU to be administered and the frequency of administration according to your individual needs. Under certain circumstances larger amounts than those calculated may be required, especially for the initial dose.

Prevention of bleeding

If you are using Helixate NexGen to prevent bleeding (prophylaxis), your doctor will calculate the dose for you. This will usually be in the range of 20 to 40 IU of octocog alfa per kg of body weight, given every of 2 to 3 days. However, in some cases, especially for younger patients, shorter dose intervals or higher doses may be necessary.

Laboratory tests

It is strongly recommended that appropriate laboratory tests be performed on your plasma at suitable intervals to ensure that adequate factor VIII levels have been reached and are maintained. For major surgery in particular, close monitoring of the substitution therapy by means of coagulation analysis must be carried out.

If bleeding is not controlled

If the factor VIII level in your plasma fails to reach expected levels, or if bleeding is not controlled after apparently adequate dose, you may have developed factor VIII inhibitors.. This must be checked by an experienced doctor.
If you have the impression that the effect of Helixate NexGen is too strong or too weak, talk to your doctor.

Patients with inhibitors

If you have been told by your doctor that you have developed factor VIII inhibitors you may need to use a larger amount of Helixate NexGen to control bleeding. If this dose does not control your bleeding your doctor may consider giving you an additional product, factor VIIa concentrate or (activated) prothrombin complex concentrate.
These treatments should be prescribed by doctors with experience in the care of patients with haemophilia A. Speak to your doctor if you would like further information on this. Do not increase your dose of Helixate NexGen you use to control your bleeding without consulting your doctor.

Speed of administration
Helixate NexGen 500 IU should be injected intravenously over several minutes. The rate of administration should be determined by the patient?s comfort level (maximal rate of infusion: 2 ml/min).

Duration of treatment

Your doctor will tell you, how often and at what intervals Helixate NexGen 500 IU is to be administered.

Usually, the substitution therapy with Helixate NexGen is a life-time treatment.

If you use more Helixate NexGen 500 IU than you should
No cases of overdose with recombinant coagulation factor VIII have been reported. If you have used more Helixate NexGen 500 IU than you should, please inform your doctor.

If you forget to use Helixate NexGen 500 IU

• Proceed with your next dose immediately and continue at regular intervals as advised by your doctor.
• Do not take a double dose to make up for a forgotten dose .

If you want to stop using Helixate NexGen 500 IUDo not stop using Helixate NexGen without consulting your doctor.

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

Like all medicines, Helixate NexGen can cause side effects, although not everybody gets them.

The frequency of possible side effects listed below is defined using the following convention: very common (affects more than 1 user in 10)
common (affects 1 to 10 users in 100)
uncommon (affects 1 to 10 users in 1,000)
rare (affects 1 to 10 users in 10,000)
very rare (affects less than 1 user in 10,000)
not known (frequency cannot be estimated from the available data).

Side effects where frequency is common:

• rash/itchy rash
• local reactions where you injected the medication (e.g. burning sensation, temporary redness)

Side effects where frequency is rare:

• hypersensitivity reactions including severe sudden allergic reaction (anaphylactic shock, e.g. tightness of the chest/general feeling of being unwell, dizziness and nausea and mildly reduced blood pressure, which may make you feel faint upon standing)
• fever

If you notice any of the following symptoms during injection/infusion:

• chest tightness/general feeling of being unwell
• dizziness
• mild hypotension (mildly reduced blood pressure, which may make you feel faint upon standing)
• nausea this can constitute an early warning for hypersensitivity and anaphylactic reactions. If allergic or anaphylactic reactions occur, the injection/infusion should be stopped immediately. Please consult your doctor immediately.

Antibodies (Inhibitors)

The formation of neutralising antibodies to factor VIII (inhibitors) is a known complication in the treatment of patients with haemophilia A. Your doctor may wish to carry out tests to monitor inhibitor development.

During clinical studies, no patient developed clinically relevant antibody titres against the trace amounts of mouse protein and hamster protein present in the preparation. However, the possibility of allergic reactions to substances contained in this medication, e.g. trace amounts of mouse and hamster protein exists in certain predisposed patients.
Your doctor may wish to carry out tests to monitor inhibitor development.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Store in a refrigerator (2°C - 8°C). Do not freeze. Keep the vials in the outer carton in order to protect from light.

You may store the product when kept in its outer carton at ambient room temperature (up to 25°C) for a single period of up to 12 months. In this case, the product expires at the end of this 12-month period; you must make a note of the new expiry date on the top of the outer carton.

Do not refrigerate the solution after reconstitution. The reconstituted solution should be used immediately. This product is for single use only. Any unused solution must be discarded.

Do not use Helixate NexGen 500 IU after the expiry date which is stated on labels and cartons. The expiry date refers to the last day of that month.

Do not use Helixate NexGen 500 IU if you notice any particles or the solution is cloudy.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Helixate NexGen 500 IU contains

Powder
The active substance is human coagulation factor VIII (octocog alfa) produced by recombinant DNA technology.
The other ingredients are glycine, sodium chloride, calcium chloride, histidine, polysorbate 80, and sucrose ( see end of Section 2).

Solvent
Water for injections, sterilised.

What Helixate NexGen 500 IU looks like and content of the pack

Helixate NexGen is provided as a powder and solvent for solution for injection and is a dry white to slightly yellow powder or cake. After reconstitution the solution is clear. Medical devices for reconstitution and administration are provided with each package of Helixate NexGen 500 IU.

Marketing Authorisation Holder

Bayer Schering Pharma AG
13342 Berlin
Germany

Manufacturer

Bayer HealthCare Manufacturing S.r.l.
Via delle Groane 126
20024 Garbagnate Milanese (MI)
Italy

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

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