Prospect: information for the user

Nuwiq 250 UI powder and solvent for injectable solution

Nuwiq 500 UI powder and solvent for injectable solution

Nuwiq 1000 UI powder and solvent for injectable solution

Nuwiq 2000 UI powder and solvent for injectable solution

Nuwiq 2500 UI powder and solvent for injectable solution

Nuwiq 3000 UI powder and solvent for injectable solution

Nuwiq 4000 UI powder and solvent for injectable solution

simoctocog alfa (human recombinant coagulation factor VIII)

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

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor.
• This medicine has been prescribed only to you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, even if they are not listed in this prospect. See section 4.

Nuwiq contains the active ingredient human coagulation factor VIII recombinant (simoctocog alfa). Factor VIII is necessary for blood to form clots and stop bleeding. In patients with hemophilia A (congenital deficiency of factor VIII), factor VIII is lacking or does not function correctly.

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

No use Nuwiq:

• If you are allergic to the active ingredient simoctocog alfa or to any of the other components of this medication (listed in section 6).

If you are unsure, ask your doctor.

Warnings and precautions

Consult 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 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 formation of inhibitors (antibodies) is a known complication that can occur during treatment with all factor VIII medications. These inhibitors, especially in large quantities, prevent the treatment from working properly, so you and your child will be closely monitored for the development of these inhibitors. If your bleeding or your child's bleeding does not control with Nuwiq, consult your doctor immediately.

Cardiovascular events

In patients with cardiovascular risk factors, restorative treatment with FVIII may increase cardiovascular risk.

Complications associated with catheters

If you require a central venous access device (CVAD), be aware of the risk of complications associated with CVAD, including localized infections, presence of bacteria in the blood, and thrombosis at the catheter implantation site.

It is strongly recommended that each time Nuwiq is administered, the product name and batch number be recorded to maintain a link between you and the medication batch.

Other medications and Nuwiq

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, consult your doctor before using this medication.

Driving and operating machinery

Nuwiq does not affect your ability to drive and operate machinery.

Nuwiq contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per vial, which is essentially "sodium-free".

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

The treatment with Nuwiq will be initiated by an experienced doctor in the care of patients with hemophilia A. Follow exactly the administration instructions of this medication indicated by your doctor or nurse. In case of doubt, consult your doctor or nurse again.

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

Your doctor will calculate your Nuwiq dose (in International Units = IU) depending on your condition and body weight, and whether it is being used for prevention or treatment of bleeding. The frequency at which you will need an injection will depend on how well Nuwiq works for you. Normally, the treatment of hemophilia A is a lifelong treatment.

Prevention of bleeding

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 necessary.

Treatment of bleeding

The dose of Nuwiq is calculated based on your body weight and the levels of factor VIII that need to be achieved. The target levels of factor VIII will 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 relevant laboratory tests to ensure that you have adequate levels of factor VIII. This is especially important if you are to undergo major surgery.

Patients who develop factor VIII inhibitors

If your plasma factor VIII does not reach the expected levels with Nuwiq, or if bleeding cannot be adequately controlled, it may be due to the development of factor VIII inhibitors. Your doctor will check for this. You may need a higher dose of Nuwiq or a different product to control bleeding. Do not increase the total dose of Nuwiq to control bleeding 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 it may be necessary to administer factor VIII medications more frequently in children and adolescents, it may be necessary to attach a central venous access device (CVAD). A CVAD is an external connector that allows access to the bloodstream through a catheter without injection through the skin

If you use more Nuwiq than you should

No symptoms of overdose have 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 compensate for missed doses. Proceed to administer the next dose immediately and continue with your doctor's recommendations.

If you interrupt treatment with Nuwiq

Do not stop treatment with Nuwiq without consulting your doctor.

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

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

Allergic Reactions

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

• eruption, hives, itchy rash, generalized itching,
• swelling of lips and tongue,
• difficulty breathing, wheezing, chest tightness,
• general feeling of discomfort,
• 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 side effects that may affect more than 1 in 10 people

Inhibitors of FVIII in untreated patients.

In children and adolescents who have not received prior treatment with factor VIII-containing medications, inhibitors (see section 2) may occur 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 infrequent (less than 1 in 100 patients). If this happens, the medications you or your child take may not work properly and you or your child may experience persistent bleeding. In that case, contact your doctor immediately.

Common side effects that may affect up to 1 in 10 people

Hyper-sensitivity, fever.

Uncommon side effects that may affect up to 1 in 100 patients

Tickling or numbness (paresthesia), headache, inflammation and/or pain at the injection site, back pain, dizziness, dry mouth, dizziness, vague feeling of bodily discomfort, shortness of breath, hemorrhagic anemia, positive results for non-neutralizing antibody formation (in PTP).

Reporting of side effects

If you experience any type of side effects, consult your doctor, even if they are possible side effects that do not appear in this prospectus. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about 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 label of the box and on the vial label after EXP. The expiration date is the last day of the month indicated.

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

Before Nuwiq powder is reconstituted, it can be stored at room temperature (up to 25°C) for a single period not exceeding 1 month. Note the date when you start storing Nuwiq at room temperature on the medication box. Do not store Nuwiq in the refrigerator again 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 medication if you observe visible signs of deterioration of the packaging seal, especially of the syringe and/or the vial.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Nuwiq

Powder:

• The active ingredient is human recombinant 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, dihydrate calcium chloride, arginine hydrochloride, dihydrate sodium citrate, and poloxamer 188. See section 2, "Nuwiq contains sodium".

Vehicle:

Water for injection

Appearance of the product and contents of the package

Nuwiq is supplied as powder and vehicle for injectable solution. The powder is white to off-white in a glass vial. The vehicle is water for injection in a preloaded glass syringe.

Once reconstituted, the solution is transparent, colorless, and free of foreign particles.

Each package of Nuwiq contains:

• 1 vial of powder with 250, 500, 1000, 2000, 2500, 3000, or 4000 IU of simoctocog alfa
• 1 preloaded syringe with 2.5 mL of water for injection
• 1 vial adapter
• 1 butterfly needle
• 2 alcohol wipes

Marketing authorization holder and responsible manufacturer

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

For more information about this medication, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet

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

This information is intended solely for healthcare professionals:

On-demand treatment

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

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

INSTRUCTIONS FOR PREPARATION AND ADMINISTRATION

1. Allow the syringe of diluent (water for injection) and the powder to reach room temperature in the closed vial. You can do this by holding them in your hands until they are at the same temperature as your hands. Do not heat the vial and syringe in any other way. This temperature should be maintained during reconstitution.
2. Remove the plastic flip-off cap from the powder vial to expose the central parts of the rubber stopper. Do not remove the gray stopper or the metal ring surrounding the top of the vial.

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

1. Place the powder vial on a flat surface and hold it in place. Take the vial adapter package and place the adapter over the center of the rubber stopper on the powder vial. Press the vial adapter package firmly down until the adapter pierces the rubber stopper. The adapter will attach to the vial when it is done.

1. Remove the paper cover from the preloaded syringe package. Hold the plunger rod by the end and do not touch the plunger. Attach the end of the plunger rod to the plunger of the syringe by twisting it in a clockwise direction until you feel a slight resistance.

1. Break the plastic protective cap off the syringe by snapping the perforation of the cap. Do not touch the inside of the cap or the syringe tip. If you do not use the solution immediately, close the syringe with the plastic protective cap to store it.

1. Remove the vial adapter packaging and discard it.
2. Attach the syringe to the vial adapter by twisting it in a clockwise direction until you feel a slight resistance.

1. Slowly inject all the diluent into the powder vial by pressing the plunger down.

1. Without removing the syringe, gently move the vial a few times to dissolve the powder. Do not shake. Wait until the powder is completely dissolved.
2. Check if the final solution has particles before administering it. The solution should be transparent, colorless, and practically free of visible particles. Do not use turbid or sediment-containing solutions.
3. Turn the vial attached to the syringe, and slowly withdraw the solution into the syringe. Make sure to transfer all the contents of the vial to the syringe.

1. Separate the syringe from the vial adapter by twisting it in a counterclockwise direction and discard the empty vial.
2. The solution is now ready for 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 chosen vein. If you have used a tourniquet to make the vein more visible, it should be loosened before starting to inject the solution.

No blood should enter the syringe due to the risk of fibrin clot formation.

1. Inject the solution into the vein slowly, not faster than 4 mL per minute.

If you use more than one vial of powder for a treatment, you can use the same needle again. The vial adapter and syringe are for single use only.