Product Information for the User

ADYNOVI 250 IU/5 ml powder and solvent for solution for injection

ADYNOVI 500 IU/5 ml powder and solvent for solution for injection

ADYNOVI 1 000 IU/5 ml powder and solvent for solution for injection

ADYNOVI 2 000 IU/5 ml powder and solvent for solution for injection

ADYNOVI 3 000 IU/5 ml powder and solvent for solution for injection

rurioctocog alfa pegol (recombinant human coagulation factor VIII pegylated)

This medicine is subject to additional monitoring, which will facilitate the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report adverse effects.

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

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor.
• This medicine has been prescribed for you only, and you must not give it to others, 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 possible adverse effects that do not appear in this leaflet. See section 4.

ADYNOVI contains the active ingredient rurioctocog alfa pegol, pegylated human coagulation factor VIII. Human coagulation factor VIII has been modified to prolong the duration of its action. Human coagulation factor VIII is necessary for blood to form clots and to stop bleeding. In patients with hemophilia A (congenital deficiency of factor VIII), it is either absent or does not function correctly.

ADYNOVI is used for the treatment and prevention of bleeding in patients 12 years of age and older with hemophilia A (an inherited bleeding disorder caused by the absence of factor VIII)

No use ADYNOVi

• if you are allergic to rurioctocog alfa pegol, octocog alfa, or any of the other components of this medication (listed in section 6)
• if you are allergic to mouse or hamster proteins

If you have any doubts, consult your doctor.

Warnings and precautions

It is essential to keep a record of the batch number of your ADYNOVI. Therefore, each time you receive a new package of ADYNOVI, note the date and batch number (which is on the packaging after the abbreviation "Batch") and store this information in a safe place.

Consult your doctor before starting to use ADYNOVI.

There is a very small risk that you may experience an anaphylactic reaction (a severe, sudden allergic reaction) to ADYNOVI. You should be aware of the initial signs of allergic reactions, such as rash, urticarial hives, itching, swelling of the lips and tongue, difficulty breathing, wheezing, chest tightness, general feeling of discomfort, and dizziness. These could be initial symptoms of anaphylactic shock. Other symptoms may include intense dizziness, loss of consciousness, and severe difficulty breathing.

If any of these symptoms appear, stop the injection immediately and consult your doctor. Severe symptoms, such as difficulty breathing and (pre)syncope, require urgent treatment.

If you have any heart disease, inform your doctor, as there is a higher risk of complications due to blood clot formation.

Patients who develop factor VIII inhibitors

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 is not being controlled with ADYNOVI, consult your doctor immediately.

Complications related to the catheterIf you need to use a central venous catheter (CVC), the risk of complications related to this device, such as local infections, presence of bacteria in the blood, and thrombosis in the catheter area, should be taken into account.

Children and adolescents

ADYNOVI can only be used in adolescents and adults (over 12 years old). The warnings and precautions listed also apply to adolescents.

Other medications and ADYNOVI

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 if you think you may be pregnant, consult your doctor before using this medication. Hemophilia A rarely affects women, so there is no experience with the use of ADYNOVI during pregnancy and breastfeeding.

Driving and operating machinery

The influence of ADYNOVI on the ability to drive and operate machinery is negligible or insignificant.

ADYNOVI contains sodium

ADYNOVI contains up to 12.42 mg of sodium (main component of table salt/for cooking) per vial. This is equivalent to 0.62% of the maximum daily sodium intake recommended for an adult. Depending on your body weight and your ADYNOVI dose, you may receive more than one vial. This should be taken into account if you follow a low-sodium diet.

Your doctor will initiate and supervise your treatment with ADYNOVI, and they should be experienced in treating patients with hemophilia A.

Your doctor will calculate your dose of ADYNOVI based on your condition and body weight, and whether it is for prevention or treatment of bleeding. The frequency of administration will depend on how ADYNOVI works in your case. ADYNOVI treatment is usually a lifelong treatment.

Follow exactly the administration instructions for this medication as indicated by your doctor. If you are unsure, consult your doctor again.

Bleeding prevention

The usual dose of ADYNOVI is 40 to 50 UI per kg of body weight, administered 2 times a week.

Bleeding treatment

The dose of ADYNOVI will be calculated based on your body weight and the desired levels of factor VIII. The desired factor VIII levels will depend on the severity and location of the bleeding.

Consult your doctor if you think the effect of ADYNOVI is insufficient.

Your doctor will perform the necessary laboratory tests to ensure you have the appropriate levels of factor VIII. This is especially important if you are undergoing major surgery.

Use in children and adolescents

ADYNOVI can only be used in adolescents and adults (over 12 years old). The dose for adolescents is also calculated based on body weight and is the same as for adults.

How to administer ADYNOVI

Normally, your doctor or nurse will inject ADYNOVI into a vein (intravenous route). You or someone else can also administer the ADYNOVI injection, but only after receiving proper training. Detailed instructions for self-administration are described at the end of this leaflet.

If you use more ADYNOVI than you should

Follow exactly the administration instructions for ADYNOVI as indicated by your doctor. Consult your doctor if you are unsure. If you inject a higher dose of ADYNOVI than recommended, consult your doctor as soon as possible.

If you forget to use ADYNOVI

Do not inject a double dose to make up for the missed dose. Administer the next injection as scheduled and continue as your doctor had instructed.

If you interrupt treatment with ADYNOVI

Do not stop using ADYNOVI without consulting your doctor.

If you have any other questions about using this medication, ask your doctor.

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

If you experiencesevere and sudden allergic reactions (anaphylaxis),stop the injection immediately.Contact your doctor immediatelyif you have any of the following initial symptoms of allergic reactions:

• eruption, urticarial rash, hives, generalized itching,
• swelling of lips and tongue,
• difficulty breathing, wheezing, chest tightness,
• general feeling of discomfort,
• dizziness and loss of consciousness.

Severe symptoms, such as difficulty breathing and near fainting, require immediate urgent treatment

In patients who have received previous treatment with factor VIII (more than 150 days of treatment), antibodies inhibitors (see section 2) may form with a low frequency (less than 1 in 100 patients). If this happens, the medicine you take may not work properly and you may experience persistent bleeding. In that case, contact your doctor immediately.

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

Headache

Frequent side effects(can affect up to 1 in 10 people)

Nausea

Diarrhea

Eruption

Dizziness

Urticarial rash

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

Redness, allergic reaction (hypersensitivity)

Factor VIII inhibitors (in patients who have received previous treatment with factor VIII (more than 150 days of treatment))

Increased levels of some white blood cells

Reaction to infusion

Eye redness

Adverse skin reaction

Other side effects in children

The frequency, type, and severity of adverse reactions in children are expected to be the same as in adults.

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational 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 and the box after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2 °C and 8 °C).

Do not freeze.

Store blister in the outer packaging to protect it from light.

During its period of validity, the vial of powder can be stored at room temperature (up to 30 °C) for a single period that does not exceed 3 months. In that case, this medication expires at the end of this 3-month period or on the expiration date printed on the product vial, whichever occurs first. Please note on the outer packaging the date of the end of the 3-month storage period at room temperature. The medication cannot be refrigerated again after being stored at room temperature. Do not refrigerate the medication after preparation.

Use the medication within 3 hours after complete dissolution of the powder.

This medication is for single use. Dispose of unused solution properly

Medicines should not be thrown away through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of ADYNOVI

• The active ingredient is rurioctocog alfa pegol (human coagulation factor VIII produced by recombinant DNA technology). Each vial of powder contains nominally 250, 500, 1,000, 2,000 or 3,000 IU of rurioctocog alfa pegol.
• The vial of solvent contains 5 ml of water for injection.

• The other ingredients are mannitol, trehalose dihydrate, histidine, glutathione, sodium chloride, calcium chloride dihydrate, tris(hydroxymethyl)aminomethane, and polisorbate 80. See section 2 “ADYNOVI contains sodium”.

Appearance of the product and contents of the pack

ADYNOVI is supplied as a powder and solvent for injection (powder for solution for injection). The powder is a white to off-white powder that dissolves. The solvent is a colourless transparent solution. After reconstitution, the solution is transparent, colourless and free of foreign particles.

Marketing authorisation holder

Baxalta Innovations GmbH

Industriestrasse 67

A-1221 Vienna

Manufacturer

Baxalta Belgium Manufacturing SA

Boulevard René Branquart 80

B-7860 Lessines

Belgium

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Last update of the summary of product characteristics:

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu/

Instructions for preparation and administration

ADYNOVI must not be mixed with other medicinal products or solvents.

It is strongly recommended to record the name and batch number of the product each time ADYNOVI is administered. The blister pack has labels that can be removed.

Instructions for reconstitution

• Do not use after the expiry date shown on the labels and the pack.
• Do not use if the blister pack is not perfectly sealed.
• Do not refrigerate the medicinal product after preparation.

1. If the medicinal product is still in the refrigerator, take the sealed blister pack (containing the vials of powder and solvent pre-assembled in the system for reconstitution) from the refrigerator and wait until it reaches room temperature (between 15 °C and 25 °C).
2. Wash hands with soap and water.
3. Open the ADYNOVI blister pack by removing the lid. Remove the BAXJECT III system from the blister pack.
4. Place the vial of powder on a flat surface with the vial of solvent on top (Figure 1). The vial of solvent has a blue stripe. Do not remove the blue cap until instructed to do so later.
5. While holding the vial of powder with one hand in the BAXJECT III system, press the vial of solvent with the other hand until the system is fully contracted and the solvent enters the vial of powder (Figure 2). Do not tilt the system until the transfer is complete.
6. Check that the transfer of the solvent is complete. Gently agitate until all the material is dissolved (Figure 3). Check that the powder is completely dissolved; if not, the entire reconstituted solution will not pass through the filter of the device. The medicinal product dissolves rapidly (usually in less than 1 minute). After reconstitution, the solution must be transparent, colourless and free of foreign particles.

Instructions for injection

During administration, a sterile technique (in conditions of cleanliness and few microorganisms) is required.

Important note:

• Examine the prepared solution for particles or colour changes before administration (the solution must be transparent, colourless and free of particles).

Do not use if the solution is not completely transparent or the product is not completely dissolved.

1. Remove the blue cap from the BAXJECT III device (Figure 4).Do not introduce air into the syringe. Connect the syringe to the BAXJECT III. It is recommended to use a Luer-lock syringe.
2. Turn the system around(the vial of powder will now be on top). Introduce the reconstituted solution into the syringe, pulling the plunger back slowly (Figure 5).
3. Disconnect the syringe, connect a needle to the syringe and inject the reconstituted solution into a vein. The solution must be administered slowly, at a rate determined by the patient's comfort level, which must not exceed 10 ml per minute. (See section 4 "Possible adverse effects").
4. Properly dispose of any unused solution.

This information is intended solely for healthcare professionals

On-demand treatment

In the case of subsequent bleeding episodes, the factor VIII activity must 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 dosing guide for surgery and bleeding episodes:

Table 1: Dosing guide for on-demand treatment in bleeding episodes and surgery

Prophylaxis

For long-term prophylaxis, the recommended dose is 40 to 50 IU of ADYNOVI per kg of body weight twice a week at intervals of 3 to 4 days. Dose adjustments and administration intervals may be considered based on factor VIII levels obtained and individual bleeding trends.

Pediatric population

The dosing guide for on-demand treatment in pediatric patients (12 to 18 years of age) is the same as for adult patients. The prophylactic treatment for patients 12 to <18>