Esperoct

Package leaflet: Information for the user

Esperoct 500 IU powder and solvent for solution for injection, 1,000 IU powder and solvent for solution for injection, 1,500 IU powder and solvent for solution for injection, 2,000 IU powder and solvent for solution for injection, 3,000 IU powder and solvent for solution for injection, 4,000 IU powder and solvent for solution for injection, 5,000 IU powder and solvent for solution for injection

turoctocog alfa pegylated (pegylated recombinant human coagulation factor VIII (rDNA))
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read all of this leaflet carefully before you start using this medicine, as it contains
important information.

• 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 only. Do not give it to others, even if they have the same symptoms as you, because it could be harmful.
• If you notice any side effect, inform your doctor. This includes any side effect not listed in this leaflet. See section 4.

Contents of this leaflet

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

1. What Esperoct is and what it is used for

What Esperoct is
Esperoct contains the active substance turoctocog alfa pegylated and is a recombinant, prolonged-acting coagulation factor VIII. Factor VIII is a protein present in the blood that helps prevent and stop bleeding.
What Esperoct is used for
Esperoct is used for the treatment or prevention of bleeding in patients of all age groups with haemophilia A (congenital factor VIII deficiency).
In people with haemophilia A, factor VIII is missing or does not function properly. Esperoct replaces this deficient or malfunctioning factor VIII and helps blood to clot at the site where bleeding occurs.

2. What you need to know before using Esperoct

Do not use Esperoct

• if you are allergic to turoctocog alfa pegylated or to any of the other ingredients of this medicine (listed in section 6)
• if you are allergic to hamster proteins.

Do not use Esperoct if any of the above conditions apply to you. If you are unsure, contact your
doctor before using this medicine.
Warnings and precautions
Prior use of factor VIII-containing medicines
Inform your doctor if you have previously used factor VIII-containing medicines, especially if you have developed
inhibitors (antibodies) against such medicines, as there is a risk this could happen again.
Allergic reactions
There is a risk of developing a severe and sudden allergic reaction (e.g. anaphylactic reaction) to
Esperoct.
If you experience any early signs of an allergic reaction, stop administration and contact your
doctor or emergency services immediately. Early signs of an allergic reaction may include
skin rash, hives, wheals, itching over large areas of the skin, redness and/or swelling of the
lips, tongue, face or hands, difficulty swallowing or breathing, wheezing, chest tightness, pale and cold skin, rapid heartbeat, dizziness, headache,
nausea and vomiting.
Development of "factor VIII inhibitors" (antibodies)
Inhibitors (antibodies) may develop during treatment with factor VIII-containing medicines.

• These inhibitors, especially at high levels, may interfere with the effectiveness of treatment.
• Monitor closely for the development of such inhibitors.
• If bleeding is not controlled with Esperoct, inform your doctor immediately.
• Do not increase the total dose of Esperoct to control bleeding without first consulting your doctor.

Catheter-related problems
If you use a catheter allowing injection of medicines into the bloodstream (central venous access
device), infections or blood clots may develop at the catheter site.
Cardiovascular diseases
Inform your doctor or pharmacist if you have cardiovascular diseases or are at risk of developing a
cardiovascular disease.
Other medicines and Esperoct
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, breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult
your doctor before taking this medicine.
Driving and using machines
Esperoct does not affect the ability to drive or operate machinery.
Decreased factor VIII activity in previously untreated patients
At the beginning of treatment, a decrease in factor VIII activity may occur. Contact your
doctor immediately if bleeding is not controlled with Esperoct.
Decreased factor VIII activity in previously treated patients
At the beginning of treatment, a decrease in factor VIII activity may occur. Contact your
doctor if bleeding is not controlled with the usual dose of Esperoct.
Esperoct 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 daily sodium intake recommended for an adult.

3. How to use Esperoct

Treatment with Esperoct should be initiated by a doctor experienced in the management of patients with haemophilia A.
Always use this medicine exactly as your doctor has instructed you. If you have any doubts about how to use Esperoct, consult your doctor.

How to administer Esperoct
Esperoct is administered by intravenous injection (into a vein). See “Instructions on how to use Esperoct” for further information.

How much medicine to use
Your doctor will calculate the required dose for you. This will depend on your body weight and whether the medicine is being used to prevent or to treat bleeding.

Prevention of bleeding
For children (under 12 years of age), the recommended dose is 65 IU of Esperoct per kg of body weight twice weekly. Your doctor may choose a different dose or frequency of injections based on your individual needs.
For adults and adolescents (12 years of age and older), the recommended dose is 50 IU of Esperoct per kg of body weight every 4 days. Your doctor may adjust the dose or frequency of administration according to your individual needs.

Treatment of bleeding
The dose of Esperoct 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. Contact your doctor if bleeding is not controlled with the usual dose of Esperoct.

Use in children and adolescents
For children (under 12 years of age), the recommended dose is 65 IU of Esperoct per kg of body weight twice weekly. Adolescents (12 years of age and older) may use the same dose as adults.

If you use more Esperoct than you should
If you use more Esperoct than prescribed, inform your doctor immediately.
Always use Esperoct exactly as your doctor has told you. Consult your doctor if you are unsure. For further information, see “Development of ‘factor VIII inhibitors’ (antibodies)” in section 2.

If you forget to use Esperoct
If you miss a dose, inject the missed dose as soon as you remember. Do not inject a double dose to make up for the forgotten dose. Continue with the next injection as scheduled and follow your doctor’s instructions. If you have any doubts, consult your doctor.

If you stop using Esperoct
Do not stop using Esperoct without first consulting your doctor.
If you discontinue treatment with Esperoct, you may no longer be protected against bleeding episodes, or ongoing bleeding may not stop. For any questions about the use of this medicine, speak to your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Allergic reactions (hypersensitivity)
Stop the infusion immediately if severe and sudden allergic reactions (anaphylactic reactions) occur. Contact your doctor or emergency services immediately if you experience any of the signs of an allergic reaction such as:

• difficulty swallowing or breathing
• wheezing
• tightness in the chest
• redness and/or swelling of the lips, tongue, face or hands
• rash, hives, wheals or itching
• pale and cold skin, rapid heartbeat, or dizziness (low blood pressure)
• headache, feeling unwell (nausea) or illness (vomiting).

Development of ‘factor VIII inhibitors’ (antibodies)
If you have previously been treated with factor VIII for more than 150 days, development of inhibitors (antibodies) may occur (this may affect up to 1 in 100 people). If this happens, the medicine may not work properly and you may experience persistent bleeding. In such a case, contact your doctor immediately. See “Development of ‘factor VIII inhibitors’ (antibodies)” in section 2.

The following side effects have been observed with Esperoct:

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

• factor VIII inhibitors (antibodies) in patients who have not been previously treated with factor VIII.

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

• skin reactions at the injection site
• itching (pruritus)
• redness of the skin (erythema)
• rash.

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

• allergic reactions (hypersensitivity). These may become severe and can be life-threatening. See “Allergic reactions (hypersensitivity)” above for further information.
• factor VIII inhibitors (antibodies) in patients previously treated with factor VIII.

Other possible side effects (frequency not known)
Decrease in factor VIII activity in the absence of factor VIII inhibitors.
At the beginning of treatment, a temporary immune response may occur, which could reduce the effectiveness of the medicine.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any side effects not listed in this leaflet. You can also report side effects directly via the 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 Esperoct

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack, the vial, and the label of the pre-filled syringe following 'EXP'. The expiry date refers to the last day of the month indicated.

Before reconstitution (before the powder is mixed with the solvent):
Store in a refrigerator (2 °C - 8 °C). Esperoct may be kept

• at room temperature (≤ 30 °C) for a single period of up to 1 year, within the product's shelf life or
• above room temperature (> 30 °C up to 40 °C) for a single period not exceeding 3 months within the product's shelf life.

When starting to store Esperoct outside the refrigerator, record the date and storage temperature in the space provided on the pack.
Once the medicine has been removed from the refrigerator for storage, it is not necessary to return it to the refrigerator. Do not freeze. Store in the original packaging to protect the medicine from light.

After reconstitution (after the powder has been mixed with the solvent – 500 IU, 1 000 IU, 1 500 IU, 2 000 IU, 3 000 IU):
Once reconstituted, Esperoct must be used immediately. If you cannot use the reconstituted solution immediately, it must be used within

• 24 hours if stored in the refrigerator (2 °C - 8 °C) or
• 4 hours if stored at ≤ 30 °C or
• 1 hour between > 30 °C and 40 °C, only if the product was stored above room temperature (> 30 °C up to 40 °C) before reconstitution for no more than 3 months.

After reconstitution (after the powder has been mixed with the solvent – 4 000 IU, 5 000 IU):
The physical and chemical stability in-use has been demonstrated for:

• 24 hours if stored in the refrigerator (2 °C - 8 °C) or
• 4 hours at ≤ 30 °C.

The powder in the vial appears white to off-white. Do not use the powder if there is any change in colour.
The reconstituted solution should be clear and colourless. Do not use the reconstituted solution if particles or changes in colour are observed.

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

6. Package contents and other information

What Esperoct contains

• The active substance is pegylated turoctocog alfa (pegylated recombinant human coagulation factor VIII (rDNA)). Each Esperoct vial contains nominally 500, 1,000, 1,500, 2,000, 3,000, 4,000 or 5,000 IU of pegylated turoctocog alfa.
• The other excipients are L-histidine, sucrose, polysorbate 80, sodium chloride, L-methionine, calcium chloride dihydrate, sodium hydroxide and hydrochloric acid.
• The ingredients in the solvent are a 9 mg/mL (0.9%) sodium chloride injectable solution and water for injections. See section 2 “Esperoct contains sodium”.

After reconstitution with the provided solvent (9 mg/mL (0.9%) sodium chloride injectable solution), the prepared injectable solution contains 125, 250, 375, 500, 750, 1,000 or 1,250 IU of pegylated turoctocog alfa per mL, respectively (based on the dose of pegylated turoctocog alfa, e.g. 500, 1,000, 1,500, 2,000, 3,000, 4,000 or 5,000 IU).

Description of the appearance of Esperoct and contents of the pack
Esperoct is available in packs containing 500 IU, 1,000 IU, 1,500 IU, 2,000 IU, 3,000 IU, 4,000 IU or 5,000 IU. Each Esperoct pack contains one vial with white or off-white powder, one 4 mL pre-filled syringe with a clear and colourless solvent, one plunger and one vial adapter.

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

Further sources of information
More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

Instructions on how to use Esperoct
Read these instructions carefully before using Esperoct.
Esperoct is supplied as a powder. Before injection, it must be reconstituted with the solvent provided in the syringe. The solvent is a 9 mg/mL (0.9%) sodium chloride injectable solution. The reconstituted medicine must be injected intravenously (intravenous injection). The components in this pack are designed to reconstitute and inject Esperoct.

You will also need:

• An infusion set (butterfly needle with tubing)
• Sterile alcohol swabs
• Gauze and adhesive bandages. These items are not included in the Esperoct pack.

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

Contents
The pack contains:

• 1 vial with Esperoct powder
• 1 vial adapter
• 1 pre-filled syringe with solvent
• 1 plunger (placed beneath the syringe)

Overview

Plunger
Thread

End

1. Prepare the vial and syringe • Remove the number of Esperoct packages needed. • 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 allow them to air dry. • Remove the vial, vial adapter, and pre-filled syringe from the packaging. Leave the plunger inside the packaging. • Bring the vial and pre-filled syringe to room temperature. This can be done by holding them in your hands until they feel as warm as your hands, see Figure A. Do not use other methods to warm the vial and pre-filled syringe.	A
Remove the plastic cap from the vial. If the plastic cap is loose or missing, do not use the vial. • Clean the vial’s rubber stopper with a sterile alcohol swab and allow it to 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.	B
2. Attach the vial adapter • Remove the protective seal from the vial adapter. If the protective seal is not tightly closed or is broken, do not use the adapter. Do not remove the vial adapter from its protective cap with your fingers. If you touch the tip of the vial adapter, germs from your fingers may be transferred.	C
Place the vial on a flat, stable surface. • Twist the protective cap to attach the adapter onto the vial. Once attached, do not remove the adapter from the vial.	D
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 off the vial when removing the protective cap.	E
3. Attach the plunger and syringe • Grasp the plunger by the end and remove it from the packaging. Do not touch the sides or threads of the plunger. If you touch the sides or threads, germs from your fingers may be transferred. • Immediately attach the plunger to the syringe by screwing it clockwise onto the piston inside the pre-filled syringe until you feel resistance.	F
Remove the cap from the pre-filled syringe by bending it downward until it breaks. Do not touch the tip of the syringe beneath the syringe cap. If you touch the syringe tip, germs from your fingers may be transferred. If the syringe cap is loose or missing, do not use the pre-filled syringe.	G
Carefully screw the pre-filled syringe onto the adapter until you feel resistance.	H
4. Reconstitute the powder with the solvent • Hold the pre-filled syringe slightly tilted with the vial pointing downward. • Push the plunger to inject all the solvent into the vial.	I
Keep the plunger fully depressed and gently swirl the vial until the powder dissolves completely. Do not shake the vial, as foam may form. • Inspect the reconstituted solution. It should be clear and colorless with no visible particles. If you notice particles or discoloration, do not use it. Instead, use a new package.	J
It is recommended to use Esperoct immediately after reconstitution. If you cannot use the reconstituted solution immediately, (applies to 500 IU, 1,000 IU, 1,500 IU, 2,000 IU, 3,000 IU) it must be used: • Within 24 hours if stored refrigerated (2°C – 8°C), or • Within 4 hours if stored at ≤ 30°C, or • Within 1 hour if stored between >30°C and 40°C, only if the product was stored above room temperature (>30°C up to 40°C) before reconstitution for no more than 3 months. If you cannot use the reconstituted solution of Esperoct immediately, (applies to 4,000 IU, 5,000 IU) it must be used within: • 24 hours if stored refrigerated (2°C – 8°C), or • 4 hours if stored at ≤ 30°C. Store the reconstituted medicine in the vial. Do not freeze the reconstituted solution or store it in the syringe. Keep the reconstituted solution protected from direct light. If your dose requires more than one vial, repeat steps A to J with additional vials, adapters, and pre-filled syringes until the required dose is reached.
Keep the plunger fully depressed. • Turn 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 not the entire contents of the reconstituted vial are needed, use the scale on the syringe to release the required dose, as directed by your doctor or nurse. If there is air in the syringe at this point, inject the air into the vial. • With the vial held downward, gently tap the syringe to move any air bubbles upward. • Slowly push the plunger until all air bubbles have disappeared.	K
Unscrew the adapter with the vial. Do not touch the tip of the syringe. If you touch the syringe tip, germs from your fingers may be transferred.	L
5. Inject the reconstituted solution Esperoct is now ready for intravenous injection. • Inject the reconstituted solution according to your doctor’s or nurse’s instructions. • Inject slowly over approximately 2 minutes. Do not mix Esperoct with another intravenous solution or with other medicines. Inject Esperoct through needle-free connectors for central venous catheters. Caution: The pre-filled 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 pre-filled syringes. This incompatibility may prevent administration of the medicine and may damage the needle-free connector. Inject the solution through a central venous access system such as a central venous catheter (central venous access device, CVC) or a subcutaneous port:
Use an aseptic, germ-free technique. Follow the instructions for correct use of the connector and central venous catheter (central venous access device, CVC) as advised by your doctor or nurse. • Injection into a CVC may require using 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 Esperoct, use an injectable sodium chloride solution 9 mg/mL (0.9%).
Disposal • After injection, dispose of any unused Esperoct 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.	M
Do not dismantle the devices before disposal. Do not reuse any materials.