Package Leaflet: Information for the User

NovoEight 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, 1500 IU powder and solvent for solution for injection, 2000 IU powder and solvent for solution for injection, 3000 IU powder and solvent for solution for injection

turoctocog 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.
This medicine has been prescribed for you personally. Never give it to others. It may be harmful to other people, even if their symptoms are the same as yours.
If you notice any side effects, inform your doctor. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet

What NovoEight is and what it is used for
What you need to know before using NovoEight
How to use NovoEight
Possible side effects
How to store NovoEight
Contents of the pack and other information

1. What NovoEight is and what it is used for

NovoEight contains the active substance turoctocog alfa, which is human coagulation factor VIII. Factor VIII is a protein naturally present in the blood that helps blood to clot. NovoEight is used in patients with haemophilia A (congenital factor VIII deficiency) for the treatment or prevention of bleeding episodes and can be used in patients of all ages. In people with haemophilia A, factor VIII is missing or does not work properly. NovoEight replaces this defective or missing factor VIII and helps blood to clot at the site where bleeding occurs.

2. What you need to know before using NovoEight

Do not use NovoEight:

if you are allergic to the active substance or to any of the other excipients of this medicine (listed in section 6)
if you are allergic to hamster proteins.

Do not use NovoEight if you have any of these conditions. If you are unsure, contact your doctor before using
this medicine.
Warnings and precautions
Consult your doctor before using NovoEight.
There is a possibility, although rare, that you may develop an anaphylactic reaction (a severe and sudden
allergic reaction) to NovoEight. The first signs of such allergic reactions include skin rash, urticaria, hives,
generalized itching, swelling of the lips and tongue, difficulty breathing, wheezing, tightness in the chest,
general feeling of discomfort, and dizziness.
If any of these symptoms occur, stop the infusion immediately and contact your doctor.
Consult your doctor if you feel that bleeding has not been controlled with the dose taken, as there may be
multiple causes. Some people using this medicine may develop antibodies against factor VIII (also known as
factor VIII inhibitors). Factor VIII inhibitors can make NovoEight less effective in preventing or controlling
bleeding. If this occurs, you may need a higher dose of NovoEight or another medicine to control bleeding.
Do not increase the total dose of NovoEight to control bleeding without first speaking to your doctor.
You must inform your doctor if you have previously been treated with factor VIII, especially if you developed
inhibitors, as their formation may reappear.
The development of inhibitors (antibodies) is a known complication that may occur during treatment with
all factor VIII-containing medicines. Inhibitors, especially at high levels, prevent the treatment from working
properly, and you or your child will be closely monitored for the development of these inhibitors. If your
bleeding or your child’s bleeding is not controlled with NovoEight, inform your doctor immediately.
Taking other medicines and NovoEight
Inform 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, suspect you may be pregnant, or are planning to become pregnant, ask
your doctor for advice before taking this medicine.
Driving and using machines
NovoEight does not affect the ability to drive or operate machinery.
NovoEight contains sodium
This medicine contains 30.5 mg of sodium (the main component of table salt) per reconstituted vial.
This corresponds to 1.5% of the maximum recommended daily dietary intake of sodium for an adult.
Consult your doctor if you are on a low-sodium diet.

3. How to use NovoEight

Treatment with NovoEight should be initiated by a doctor experienced in the treatment of patients with haemophilia A. Always use this medicine exactly as instructed by your doctor. If you are unsure, check with your doctor.
Your doctor will determine the dose you need based on your body weight and the treatment regimen used.

Prevention of bleeding
The usual dose of NovoEight is between 20 and 50 international units (IU) per kg of body weight, injected every 2–3 days. In some cases, especially in younger patients, more frequent injections or higher doses may be required.

Treatment of bleeding episodes
The dose of NovoEight is calculated based on body weight and the factor VIII levels that need to be achieved. The optimal factor VIII levels will depend on the severity and location of the bleeding.

Use in children and adolescents
NovoEight can be used in children of all ages. Higher doses or more frequent injections may be necessary in younger children (under 12 years of age). Adolescents (over 12 years of age) may use the same dose as adults.

How to take NovoEight
NovoEight is administered by intravenous injection. For further information, see “Instructions on how to use NovoEight”.

If you take more NovoEight than you should
If you take more NovoEight than you should, inform your doctor and go to hospital immediately.

If you forget to use NovoEight
If you have missed a dose of NovoEight and are unsure how to make up for the missed dose, consult your doctor.

If you stop using NovoEight
If you stop using NovoEight, you may no longer be protected against bleeding, and any subsequent bleeding may not stop.
Do not stop using NovoEight without first consulting your doctor.

If you have any doubts about how to use this medicine, speak to your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may occur with this medicine.
If you experience severe and sudden allergic reactions (anaphylactic reactions) (very rare), you must stop the infusion immediately. If you notice any of the following early symptoms, contact your doctor immediately:

difficulty breathing, shortness of breath, or wheezing
tightness in the chest
swelling of the lips and tongue
skin rash, hives, wheals, and generalized itching
dizziness or loss of consciousness
low blood pressure (pale and cold skin, increased heart rate).

Severe symptoms, including difficulty swallowing and breathing, redness or swelling of the face or hands, require immediate emergency treatment.
If you have a severe allergic reaction, your doctor may switch you to another medicine.
In children previously untreated with Factor VIII, inhibitor antibodies may develop (see section 2) with very common frequency (more than 1 in 10 people); however, in patients who have received prior treatment with Factor VIII (more than 150 exposure days), the risk is uncommon (less than 1 in 100 patients). If this happens to you or your child, the medicine may not work properly and you or your child may experience persistent bleeding. If this occurs, contact your doctor immediately.

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

blood tests showing changes in liver function
reactions (redness and itching) at the injection site.

Common side effects (may affect up to 1 in 10 people) in patients previously untreated with Factor VIII

skin redness
inflammation of the veins (phlebitis)
bleeding into joints
bleeding into muscle tissue
cough
redness at the catheter site
vomiting.

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

fatigue
headache
dizziness
difficulty sleeping (insomnia)
increased heart rate
increased blood pressure
rash
fever
hot flushes
muscle stiffness
muscle pain
pain in arms and legs
swelling of legs and feet
arthralgia
bruising
myocardial infarction.

Side effects in children and adolescents
The side effects observed in children and adolescents are the same as those observed in adults.

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

5. How to store NovoEight

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated after 'EXP.' on the packaging and on the label of the vial and pre-filled syringe. The expiry date refers to the last day of the month indicated.
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
Before reconstitution, NovoEight powder may be stored:

at room temperature (≤ 30°C) for a single period not exceeding 9 months or
above room temperature (from 30°C up to 40°C) for a single period not exceeding 3 months

Once the product has been removed from the refrigerator, it must not be returned to refrigerated storage.
Record the start date of the storage period and the storage temperature on the packaging.
After reconstitution, NovoEight must be used immediately. If immediate use is not possible, the reconstituted solution may be used within:

24 hours when stored at 2°C – 8°C
4 hours when stored at 30°C, for the product that has been kept for a single period not exceeding 9 months at room temperature (≤ 30°C)
4 hours when stored up to 40°C, for the product that has been kept for a single period not exceeding 3 months above room temperature (from 30°C up to 40°C)

Store the reconstituted medicine in the vial. If you do not use the medicine immediately, it may no longer be sterile and could cause infections. Do not store the solution without medical advice.
The powder in the vial appears white or slightly yellow. Do not use the powder if there has been a change in colour.
The reconstituted solution is clear or slightly opalescent. Do not use this medicine if the solution appears cloudy or contains visible particles.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What NovoEight contains

The active substance is turoctocog alfa (recombinant human coagulation factor VIII (rDNA)). Each NovoEight vial contains nominally 250, 500, 1000, 1500, 2000 or 3000 IU of turoctocog alfa.
The other excipients are L-histidine, sucrose, polysorbate 80, sodium chloride, L-methionine, calcium chloride dihydrate, sodium hydroxide and hydrochloric acid.
The excipients in the solvent are sodium chloride and water for injections.

After reconstitution with the provided solvent (injection solution of sodium chloride 9 mg/ml (0.9%)), the prepared injection solution contains 62.5, 125, 250, 375, 500 or 750 IU of turoctocog alfa per ml, respectively (based on the turoctocog alfa dosage of 250, 500, 1000, 1500, 2000 or 3000 IU).

Description of the appearance of NovoEight and contents of the pack
NovoEight consists of powder and solvent for injection solution.
Each NovoEight pack contains one vial with white or slightly yellow powder, one pre-filled syringe containing 4 ml of a clear, colourless solution, one plunger and one vial adapter.

Marketing Authorisation Holder:
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd, Denmark

This leaflet was last revised on
Further sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency (EMA) http://www.ema.europa.eu.

Instructions for using NovoEight
READ THESE INSTRUCTIONS CAREFULLY BEFORE USING NOVOEIGHT.
NovoEight is supplied as a powder. Before injection (administration), you must reconstitute it with the solvent provided in the syringe. The solvent is a solution of sodium chloride 9 mg/ml (0.9%). Reconstituted NovoEight must be injected intravenously (intravenous injection). The materials included in this pack are designed for reconstituting and injecting NovoEight.

You will also need an infusion set (tubing and butterfly needle), sterile alcohol swabs, gauze and adhesive bandages. These devices are not included in the NovoEight pack.

Do not use the materials without adequate training from your doctor or nurse.
Always wash your hands and ensure that the area around you is clean.
When preparing and injecting a medicine directly into a vein, it is important to use an aseptic, germ-free technique. Improper technique may introduce germs that could infect the bloodstream.
Do not open the materials until you are ready to use them.
Do not use the materials if they have been dropped or damaged. Instead, use a new pack.
Do not use the materials after the expiry date. Instead, use a new pack. The expiry date is printed after 'EXP.' on the outer packaging, vial, vial adapter and pre-filled syringe.
Do not use the materials if you suspect contamination. Instead, use a new pack.
Do not discard any of the components until after you have injected the reconstituted solution.
The materials are for single use only.

Contents
The pack contains:

1 vial with NovoEight powder
1 vial adapter
1 pre-filled syringe with solvent
1 plunger (stored under the syringe)

OverviewVial with NovoEight powderPlastic capRubber stopper (under the plastic cap)Protective capVial adapterTip (under the protective seal)Protective seal
Syringe capSyringe tip (under the syringe cap)Prefilled syringe with solventScalePlungerThreadPistonTip
1. Prepare the vial and syringe •Take out the number of NovoEight packages you need. •Check the expiration date. •Check the name, dosage, and color of the packaging to ensure it contains the correct product. •Wash your hands and dry them thoroughly with a clean towel or hand dryer. •Remove the vial, vial adapter, and prefilled syringe from the packaging. Leave the plunger inside the packaging. •Bring the vial and syringe to room temperature. You can do this by holding them in your hands until they feel as warm as your hands.
Do not use other methods to warm the vial and prefilled syringe.
Remove the plastic cap from the vial. If the plastic cap is loose or missing, do not use the vial. •Clean the rubber stopper of the vial with a sterile alcohol swab and let it air dry for a few seconds before use to ensure it is germ-free. •Do not touch the rubber stopper with your fingers, as this may transfer germs.
2. Attach the vial adapter •Remove the protective seal from the vial adapter. If the protective seal is not tightly closed or is damaged, do not use the adapter. Do not remove the adapter from the protective cap with your fingers. If you touch the tip of the vial adapter, germs from your fingers may be transferred.
Place the vial on a flat, solid surface. •Twist the protective seal and attach the adapter onto the vial. •Once attached, do not remove the adapter from the vial.
Gently press the protective cap with your thumb and index finger as shown. Remove the protective cap from the adapter. Do not lift the adapter from the vial when removing the protective cap.	E
3. Attach the plunger and syringe •Grasp the plunger by the end and pull it out of the packaging. Do not touch the parts or threads of the plunger. If you do, germs from your fingers may be transferred.
Immediately attach the plunger to the syringe by screwing it clockwise onto the piston inside the prefilled syringe until you feel resistance.
Remove the syringe cap from the prefilled syringe by bending it downward until it breaks. •Do not touch the syringe tip under the syringe cap. If you do, germs from your fingers may be transferred. •If the syringe cap is loose or missing, do not use the prefilled syringe.
Carefully screw the prefilled syringe onto the adapter until you feel resistance.
4. Reconstitute the powder with the solvent •Hold the prefilled syringe slightly tilted with the vial pointing downward. •Push the plunger to inject all the solvent into the vial.
Keep the plunger fully depressed and gently rotate the vial until the powder is completely dissolved. •Do not shake the vial, as this may cause foaming. •Inspect the reconstituted solution. It should be clear with a slightly opalescent (slightly cloudy) appearance. If you see visible particles or color changes, do not use it. Instead, use a new package.
NovoEight must be used immediately after reconstitution. If not used promptly, the medicine may no longer be sterile and could cause infections. If you cannot use the reconstituted NovoEight solution immediately, it must be used within 4 hours if stored at room temperature or up to 40°C, or within 24 hours if stored between 2°C – 8°C. Store the reconstituted medicine in the vial. Do not freeze the reconstituted NovoEight solution or store it in the syringe. Do not store the solution without medical advice. Protect the reconstituted NovoEight solution from light. If your dose requires more than one vial, repeat steps A to J with additional vials, adapters, and prefilled syringes until the required dose is reached.
Keep the plunger fully depressed. •Rotate the syringe with the vial pointing downward. •Stop pushing the plunger and let it return on its own as the reconstituted solution fills the syringe. •Gently pull back the plunger to draw the reconstituted solution into the syringe. •If you need only part of the full dose, use the scale on the syringe to determine how much reconstituted solution to administer, according to instructions provided by your doctor or nurse. If there is too much air in the syringe at this point, inject the air into the vial.
With the vial pointing downward, gently tap the syringe to allow any air bubbles to rise to the top. •Slowly push the plunger until all air bubbles have been expelled.
Unscrew the adapter with the vial. •Do not touch the syringe tip. If you do, germs from your fingers may be transferred.
5. Inject the reconstituted solution NovoEight is now ready for intravenous injection. •Inject the reconstituted solution according to your doctor’s or nurse’s instructions. •Inject slowly over 2–5 minutes. •Do not mix NovoEight with another intravenous solution or with other medicines. Inject NovoEight through needle-free connectors for central venous catheters. Caution: The prefilled syringe is made of glass and is designed to be compatible with standard luer-lock connectors. Some needle-free connectors with an internal tip are not compatible with prefilled syringes. This incompatibility may prevent administration of the medicine and/or damage the needle-free connector. Inject the solution through a central venous access system (CVC), such as a central venous catheter or implanted port: •Use an aseptic, germ-free technique. Follow instructions for the correct use of the connector and central venous catheter (CVC) as advised by your doctor or nurse. •Injection into a CVC may require the use of a sterile 10 ml plastic syringe to withdraw the reconstituted solution. This step should be performed after step J. •If the CVC tubing needs to be flushed before and after injection with NovoEight, use an injectable sodium chloride 9 mg/ml solution.
Disposal •After injection, dispose of all unused NovoEight solution, the syringe with infusion set, the vial with adapter, and other waste materials as instructed by your pharmacist. Do not dispose of them with household waste.