Adynovii 3000 IU/5 ml powder and solvent for solution for injection

Patient Information Leaflet

Introduction

Patient Information Leaflet

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 pegylated human coagulation factor VIII)

This medicinal product is subject to additional monitoring, which will allow quicker detection of new safety information. You can help by reporting any adverse reactions you may experience. Information on how to report adverse reactions is included at the end of section 4.

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

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, since it could harm them.
• If you experience any adverse reactions, consult your doctor, even if they are possible adverse reactions not listed in this leaflet. See section 4.

Leaflet Contents

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

1. What ADYNOVI is and what it is used for

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

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

2. What you need to know before using ADYNOVI

Do not use ADYNOVI

• if you are allergic to rurioctocog alfa pegol, octocog alfa, or to any of the other ingredients of this medicine (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 important to keep a record of the batch number of your ADYNOVI. Therefore, each time you receive a new ADYNOVI package, write down the date and the batch number (shown on the outer packaging after the abbreviation “Lote”) and keep 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 sudden, severe allergic reaction) to ADYNOVI. You should be aware of the early signs of allergic reactions, such as rash, hives, welts, widespread itching, swelling of the lips and tongue, difficulty breathing, wheezing, chest tightness, general feeling of discomfort, and dizziness. These could be early symptoms of anaphylactic shock. Other symptoms may include severe dizziness, loss of consciousness, and severe difficulty breathing.

If any of these symptoms occur, stop the infusion immediately and contact your doctor. Severe symptoms such as difficulty breathing and (pre) fainting require urgent medical treatment.

If you have any heart condition, inform your doctor, as there is an increased risk of complications due to blood clot formation.

Patients who develop factor VIII inhibitors

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 closely monitored for the development of such inhibitors. If your bleeding or your child's bleeding is not controlled with ADYNOVI, contact your doctor immediately.

Catheter-related complications If a central venous catheter (CVC) is required, the risk of complications related to the device should be considered, such as local infections, presence of bacteria in the blood (bacteraemia), and catheter-site thrombosis.

Children and adolescents

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

Other medicines and ADYNOVI

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, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine. Haemophilia A rarely affects women. Therefore, there is no experience regarding the use of ADYNOVI during pregnancy and breastfeeding.

Driving and using machines

The influence of ADYNOVI on the ability to drive and operate machinery is negligible or none.

ADYNOVI contains sodium

ADYNOVI contains up to 12.42 mg of sodium (a main component of table/cooking salt) per vial. This corresponds 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 are on a low-salt diet.

3. How to use ADYNOVI

Treatment with ADYNOVI will be initiated and supervised by a physician experienced in the treatment of patients with haemophilia A.

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

Always follow your doctor's instructions for administering this medicine exactly. If you are unsure, consult your doctor again.

Prevention of bleeding

The usual dose of ADYNOVI is 40 to 50 IU per kg of body weight, administered twice weekly.

Treatment of bleeding

The ADYNOVI dose is calculated based on your body weight and the desired factor VIII levels. The target 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 appropriate laboratory tests to ensure you have adequate factor VIII levels. 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 of age). The dose for adolescents is also calculated according to body weight and is the same as for adults.

How ADYNOVI is administered

ADYNOVI is normally injected into a vein (intravenous route) by a doctor or nurse. You or another person may also administer the injection yourself, 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

Always follow your doctor's administration instructions for ADYNOVI exactly. If you have any doubts, consult your doctor. If you inject more ADYNOVI than recommended, contact your doctor as soon as possible.

If you forget to use ADYNOVI

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

If you stop treatment with ADYNOVI

Do not stop using ADYNOVI without consulting your doctor.

If you have any further 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.

If severe and sudden allergic (anaphylactic) reactions occur, the injection must be stopped immediately. Contact your doctor immediately if you experience any of the following initial symptoms of allergic reactions:

• rash, urticarial wheals, hives, generalized itching,
• swelling of lips and tongue,
• difficulty breathing, noisy breathing, chest tightness,
• feeling of general malaise,
• dizziness and loss of consciousness.

Severe symptoms such as difficulty breathing and (near-)fainting require immediate emergency treatment.

In patients who have received prior treatment with factor VIII (more than 150 days of treatment), inhibitor antibodies may develop infrequently (less than 1 in 100 patients) (see section 2). If this occurs, the medicine you are taking may no longer work properly and you may experience persistent bleeding. In this case, contact your doctor immediately.

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

Headache

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

Nausea

Diarrhea

Rash

Dizziness

Urticarial wheals

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

Flushing, allergic reaction (hypersensitivity)

Factor VIII inhibitors (in patients previously treated with factor VIII (more than 150 days of treatment))

Increase in certain types of white blood cells

Infusion-related reaction

Eye redness

Adverse drug reaction of the skin

Other adverse effects in children

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of ADYNOVI

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the label and the carton after EXP. The expiry date refers to the last day of the month indicated.

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

Do not freeze.

Keep the blister pack in the outer packaging to protect it from light.

During its shelf life, the powder vial may be stored at room temperature (up to 30 °C) for a single period not exceeding 3 months. In such case, this medicine will expire at the end of this 3-month period or on the expiry date printed on the product vial, whichever comes first. Please record the end date of the 3-month room temperature storage period on the outer packaging. The medicine must not be refrigerated again after being stored at room temperature. Do not refrigerate the medicine after reconstitution.

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

This medicine is for single use only. Dispose of any unused solution appropriately.

Medicines should 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. Contents of the container and other information

Composition of ADYNOVI

• The active substance is rurioctocog alfa pegol (recombinant DNA-derived human coagulation factor VIII). Each vial of powder contains nominally 250, 500, 1,000, 2,000 or 3,000 IU of rurioctocog alfa pegol.

• The solvent vial contains 5 ml of water for injections.

• The other ingredients are mannitol, trehalose dihydrate, histidine, glutathione, sodium chloride, calcium chloride dihydrate, tris(hydroxymethyl)aminomethane and polysorbate 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 solution for injection (powder for solution for injection). The powder is a white to off-white, friable powder. The solvent is a clear, colourless solution. After reconstitution, the solution is clear, colourless and free from 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

Further information on this medicinal product is available upon request from the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

Detailed information on this medicine 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 includes labels that can be removed.

Instructions for reconstitution

• Do not use after the expiry date stated on the labels and packaging.
• Do not use if the blister seal is not intact.
• Do not refrigerate the medicine after preparation.

1. If the medicine is still in the refrigerator, remove the sealed blister (containing the preassembled vials of powder and solvent in the reconstitution system) and allow it to reach room temperature (between 15 °C and 25 °C).
2. Wash hands with soap and lukewarm water.
3. Open the ADYNOVI blister by removing the lid. Remove the BAXJECT III system from the blister.
4. Place the vial of powder on a flat surface with the solvent vial on top (Figure 1). The solvent vial has a blue mark. Do not remove the blue protector until instructed later.
5. While holding the powder vial steady with one hand in the BAXJECT III system, press firmly with the other hand on the solvent vial until the system is fully compressed and the solvent flows into the powder vial (Figure 2). Do not tilt the system until the transfer is complete.
6. Check that transfer of the solvent is complete. Gently swirl until all material is dissolved (Figure 3). Check that the powder is completely dissolved; if not, the entire reconstituted solution will not pass through the filter in the device. The medicine dissolves rapidly (usually within less than 1 minute). After reconstitution, the solution should be clear, colourless, and free from foreign particles.

Instructions for injection

An aseptic technique (clean conditions with minimal germs) must be used during administration.

Important note:

• Examine the prepared solution for particles or discoloration before administration (the solution should be clear, colourless, and free from particles).

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

1. Remove the blue protector from the BAXJECT III device (Figure 4). Do not introduce air into the syringe. Attach the syringe to the BAXJECT III. Use of a Luer-lock syringe is recommended.
2. Turn the system upside down (the powder vial will now be on top). Draw the reconstituted solution into the syringe by slowly pulling back the plunger (Figure 5).
3. Disconnect the syringe, attach a butterfly needle to the syringe, and inject the reconstituted solution into a vein. The solution should be administered slowly, at a rate determined by patient comfort, not exceeding 10 ml per minute. (See section 4 "Possible side effects").
4. Dispose of any unused solution appropriately.

This information is intended for healthcare professionals only.

On-demand treatment

For the following bleeding episodes, factor VIII activity should not fall below the plasma activity level (expressed as % of normal or IU/dl) indicated for the corresponding time period. The following table may be used as a dosing guideline for surgery and bleeding episodes:

Table 1: Dosing guideline for bleeding episodes and surgery

Prophylaxis

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

Paediatric population

The dosing regimen for on-demand treatment in paediatric patients (12 to 18 years of age) is the same as for adult patients. Prophylactic treatment for patients aged 12 to <18 years is the same as for adult patients. The long-term safety of ADYNOVI in children under 12 years of age has not yet been established. Dose adjustments and administration intervals may be considered based on obtained factor VIII levels and individual bleeding tendency.