Nuwiq 3000 IU powder and solvent for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Nuwiq 250 IU powder and solvent for solution for injection

Nuwiq 500 IU powder and solvent for solution for injection

Nuwiq 1000 IU powder and solvent for solution for injection

Nuwiq 2000 IU powder and solvent for solution for injection

Nuwiq 2500 IU powder and solvent for solution for injection

Nuwiq 3000 IU powder and solvent for solution for injection

Nuwiq 4000 IU powder and solvent for solution for injection

simoctocog alfa (recombinant human coagulation factor VIII)

Read the entire leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions about the use of this medicine, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Nuwiq is and what it is used for

Nuwiq contains the active substance recombinant human coagulation factor VIII (simoctocog alfa). Factor VIII is required for blood to form clots and stop bleeding. In patients with haemophilia A (congenital factor VIII deficiency), factor VIII is missing or does not function properly.

Nuwiq replaces the missing factor VIII and is used for the treatment and prevention of bleeding in patients with haemophilia A and can be used in all age groups.

2. What you need to know before using Nuwiq

Do not use Nuwiq:

• if you are allergic to the active substance simoctocog alfa or to any of the other ingredients of this medicine (listed in section 6).

If you are unsure, ask your doctor.

Warnings and precautions

Talk to your doctor or nurse before starting to use Nuwiq.

There is a rare possibility that you may experience an anaphylactic reaction (a sudden, severe allergic reaction) to Nuwiq. You should be able to recognize the early symptoms of allergic reactions, which are listed in section 4, "Allergic reactions".

If any of these symptoms occur, stop the injection immediately and contact your doctor.

The development of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII-containing medicines. These inhibitors, especially when present in high amounts, can prevent the treatment from working properly. Therefore, you and your child will be carefully monitored for the development of such inhibitors. If your bleeding or your child's bleeding is not controlled with Nuwiq, consult your doctor immediately.

Cardiovascular events

In patients with existing cardiovascular risk factors, replacement therapy with FVIII may increase cardiovascular risk.

Catheter-related complications

If you require a central venous access device (CVAD), the risk of CVAD-related complications, including localized infections, presence of bacteria in the blood, and thrombosis at the catheter site, should be considered.

It is strongly recommended that each time Nuwiq is administered, the name and batch number of the product be recorded to maintain traceability between you and the medicine batch.

Use of Nuwiq with other medicines

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

Pregnancy and breastfeeding

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

Driving and using machines

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

Nuwiq contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial, i.e., essentially "sodium-free".

However, depending on your body weight and dosage, you may be administered more than one vial, which should be taken into account if you are on a low-sodium diet.

3. How to use Nuwiq

Treatment with Nuwiq will be initiated by a physician experienced in the care of patients with haemophilia A. Always follow exactly the instructions for administration of this medicine given by your doctor or nurse. If in doubt, consult your doctor or nurse.

Nuwiq is normally injected into a vein (intravenously) by your doctor or a nurse experienced in the care of patients with haemophilia A. You or another person may also inject Nuwiq, but only after receiving proper training.

Your doctor will calculate your dose of Nuwiq (in International Units = IU) depending on your condition and body weight, and whether it is being used for prophylaxis or for treatment of bleeding episodes. The frequency with which you will need an injection depends on how well Nuwiq works for you. Usually, treatment of haemophilia A is a lifelong treatment.

Prevention of bleeding episodes

The usual dose of Nuwiq is 20 to 40 IU per kg of body weight, administered every 2 to 3 days. However, in some cases, especially in younger patients, more frequent injections or higher doses may be required.

Treatment of bleeding episodes

The dose of Nuwiq is calculated based on your body weight and the factor VIII levels that need to be achieved. Target factor VIII levels depend on the severity and location of the bleeding.

If you feel that the effect of Nuwiq is insufficient, consult your doctor. Your doctor will perform appropriate laboratory tests to ensure that you have adequate factor VIII levels. This is especially important if you are undergoing major surgery.

Patients who develop factor VIII inhibitors

If your plasma factor VIII does not reach the expected levels with Nuwiq, or if bleeding episodes are not adequately controlled, this may be due to the development of factor VIII inhibitors. Your doctor will check for this. You may require a higher dose of Nuwiq or a different product to control bleeding episodes. Do not increase the total dose of Nuwiq to control your bleeding episodes without consulting your doctor.

Use in children and adolescents

The way Nuwiq is used in children and adolescents does not differ from the way it is used in adults. Since factor VIII medicines may need to be administered more frequently in children and adolescents, a central venous access device (CVAD) may be required. A CVAD is an external connector that allows access to the bloodstream via a catheter without injecting through the skin.

If you use more Nuwiq than you should

Symptoms of overdose have not been reported. If you have injected more Nuwiq than you should, inform your doctor.

If you forget to use Nuwiq

Do not take a double dose to make up for a missed dose. Administer the next dose immediately and continue following your doctor's recommendations.

If you stop using Nuwiq

Do not stop treatment with Nuwiq without consulting your doctor.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Allergic reactions

You should be able to recognize the early symptoms of allergic reactions. If sudden severe allergic (anaphylactic) reactions (very rare, may affect up to 1 in 10,000 people) occur, the injection must be stopped immediately. Contact your doctor immediately if you notice any of the following symptoms:

• rash, skin eruption, hives, generalized itching,
• swelling of lips and tongue,
• difficulty breathing, wheezing, chest tightness,
• feeling generally unwell,
• dizziness and loss of consciousness.

These symptoms may be early signs of anaphylactic shock. If any of these symptoms occur, stop the injection immediately and contact your doctor. Severe symptoms require immediate emergency treatment.

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

FVIII inhibitors in previously untreated patients.

In children and adolescents who have not previously received treatment with factor VIII-containing medicines, inhibitory antibodies may develop very commonly (in more than 1 in 10 patients).

However, in patients who have previously received factor VIII treatment (more than 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). If this occurs, the medicines you or your child are taking may no longer work properly, and you or your child may experience persistent bleeding. In such a case, contact your doctor immediately.

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

Hypersensitivity, fever.

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

Tingling or numbness (paraesthesia), headache, swelling and/or pain at the injection site, back pain, dizziness, dry mouth, haemorrhagic anaemia, positive results for formation of non-neutralizing antibodies (in PTP).

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Nuwiq

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 vial label following the abbreviation EXP. The expiry date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C). Do not freeze. Keep the vial in its original packaging to protect it from light.

Before reconstitution, Nuwiq powder may be stored at room temperature (up to 25°C) for a single period not exceeding 1 month. Record the date when storage at room temperature is started on the medicine packaging. Do not return Nuwiq to the refrigerator after it has been stored at room temperature.

Use the reconstituted solution immediately after reconstitution.

Warnings regarding certain visible signs of deterioration

Do not use this medicine if there are visible signs of tampering with the container closure, particularly the syringe and/or the vial.

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

6. Contents of the pack and other information

Composition of Nuwiq

Powder:

• The active substance is recombinant human coagulation Factor VIII (simoctocog alfa). Each vial of powder contains 250, 500, 1000, 2000, 2500, 3000 or 4000 IU of simoctocog alfa.

Each reconstituted solution contains approximately 100, 200, 400, 800, 1000, 1200 or 1600 IU/ml of simoctocog alfa.

• The other components are sucrose, sodium chloride, calcium chloride dihydrate, arginine hydrochloride, sodium citrate dihydrate and poloxamer 188. See section 2, "Nuwiq contains sodium".

Solvent:

Water for injections

Appearance of Nuwiq and contents of the pack

Nuwiq is supplied as a powder and solvent for injectable solution. The powder is white to off-white in a glass vial. The solvent is water for injections in a pre-filled glass syringe.

After reconstitution, the solution is clear, colourless and free from foreign particles.

Each pack of Nuwiq contains:

• 1 vial of powder containing 250, 500, 1000, 2000, 2500, 3000 or 4000 IU of simoctocog alfa
• 1 pre-filled syringe with 2.5 ml of water for injections
• 1 vial adapter
• 1 butterfly needle
• 2 alcohol wipes

Marketing Authorisation Holder and Manufacturer

Octapharma AB, Lars Forssells gata 23, 112 75 Stockholm, Sweden

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

Date of the most recent review of this package leaflet

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

This information is intended for healthcare professionals only:

On-demand treatment

The dose to be administered and the frequency of administration should always be guided by the clinical efficacy in each individual case.

In the case of the following bleeding episodes, factor VIII activity should not be lower than the plasma activity level indicated (in % of normal or IU/dL) during the corresponding period. The following table may be used as a dosing guideline for surgery and bleeding episodes.

INSTRUCTIONS FOR PREPARATION AND ADMINISTRATION

1. Allow the solvent syringe (water for injectable preparations) and the powder vial to reach room temperature while still in their closed packaging. You may do this by holding them in your hands until they reach hand temperature. Do not heat the vial or the prefilled syringe by any other method. This temperature must be maintained during reconstitution.
2. Remove the flip-off plastic cap from the powder vial to expose the central portion of the rubber stopper. Do not remove the gray stopper or the surrounding metal ring from the top of the vial.

1. Clean the top of the vial with an alcohol wipe. Allow the alcohol to dry completely.
2. Remove the paper cover from the vial adapter package. Do not remove the adapter from its packaging.

1. Place the powder vial on a flat surface and hold it securely. Take the adapter package and place the vial adapter onto the center of the rubber stopper of the powder vial. Press the adapter package firmly downward until the tip of the adapter penetrates the rubber stopper. The adapter will be secured to the vial once this is done.

1. Remove the paper cover from the prefilled syringe package. Hold the syringe plunger rod by the end and do not touch the shaft. Attach the threaded end of the plunger rod to the solvent syringe plunger. Rotate the plunger rod clockwise until you feel slight resistance.

1. Break the seal of the plastic protective tip on the solvent syringe by snapping off the break-off portion of the closure cap. Do not touch the inside of the closure cap or the syringe tip. If the solution is not used immediately, cover the filled syringe with the plastic protective tip for storage.

1. Remove the adapter packaging and discard it.
2. Firmly attach the solvent syringe to the vial adapter by turning clockwise until slight resistance is felt.

1. Slowly inject all of the solvent into the powder vial by pressing the plunger rod downward.

1. Without removing the syringe, gently swirl or rotate the vial several times to dissolve the powder. Do not shake. Wait until all the powder is completely dissolved.
2. Check the final solution for particles before administration. The solution should be clear and colorless, practically free of visible particles. Do not use cloudy solutions or those containing sediment.
3. Turn the vial, which is still attached to the syringe, upside down and slowly withdraw the solution into the syringe. Ensure that all contents of the vial are transferred into the syringe.

1. Detach the filled syringe from the vial adapter by turning counterclockwise and discard the empty vial.
2. The solution is now ready for immediate use. Do not refrigerate.
3. Clean the chosen injection site with one of the provided alcohol wipes.
4. Attach the provided injection kit to the syringe.

Insert the needle of the injection kit into the selected vein. If a tourniquet was used to make the vein more visible, it must be loosened before beginning to inject the solution.

Blood should not enter the syringe due to the risk of fibrin clot formation.

1. Inject the solution into the vein slowly, at a rate no faster than 4 mL per minute.

If more than one powder vial is used for a treatment, the same needle may be reused. The vial adapter and syringe are for single use only.