Advate 3000 IU powder and solvent for solution for injection

Package Leaflet: Information for the User

Introduction

Package Leaflet: Information for the User

ADVATE 250 IU powder and solvent for solution for injection

ADVATE 500 IU powder and solvent for solution for injection

ADVATE 1000 IU powder and solvent for solution for injection

ADVATE 1500 IU powder and solvent for solution for injection

ADVATE 2000 IU powder and solvent for solution for injection

ADVATE 3000 IU powder and solvent for solution for injection

Octocog alfa (recombinant human coagulation factor VIII)

Read the entire 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 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, because it may 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.

Contents of the leaflet:

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

1. What ADVATE is and what it is used for

ADVATE contains the active substance octocog alfa, recombinant human coagulation factor VIII produced using recombinant DNA technology. Factor VIII is necessary for blood clotting and stopping bleeding. In patients with haemophilia A, factor VIII is missing or does not function properly (hereditary factor VIII deficiency).

ADVATE is used for the treatment and prevention of bleeding episodes in patients of all age groups with haemophilia A (an inherited bleeding disorder caused by the absence of factor VIII).

ADVATE is manufactured without the addition of any human- or animal-derived proteins at any stage of the production process.

2. What you need to know before using ADVATE

Do not use ADVATE

• if you are allergic (hypersensitive) to octocog alfa or to any of the other components of this medicine (listed in section 6).
• if you are allergic to mouse or hamster proteins

If you are unsure whether you are allergic, consult your doctor.

Warnings and precautions

Talk to your doctor before starting to use ADVATE. Inform your doctor if you have previously been treated with medicines containing factor VIII, especially if you developed inhibitors, as there may be an increased risk of this happening again. Inhibitors are antibodies that block factor VIII, reducing the effectiveness of ADVATE in controlling bleeding. The development of inhibitors is a known complication in the treatment of haemophilia A. If your bleeding does not stop with ADVATE, contact your doctor immediately.

There is a very low risk that you may experience an anaphylactic reaction (a sudden, severe allergic reaction) to ADVATE. You should be aware that early symptoms of an allergic reaction include rash, itching, hives, generalized itching, swelling of the lips and tongue, difficulty breathing, wheezing, chest tightness, general feeling of discomfort, and dizziness. These symptoms may be warning signs of anaphylactic shock, which can also cause severe dizziness, loss of consciousness, and serious breathing difficulties.

If you experience any of these symptoms, stop administering the medicine immediately and contact a doctor. Severe symptoms, including difficulty breathing and (near) fainting, require immediate emergency treatment.

Patients who develop Factor VIII inhibitors

The formation of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII-containing medicines. These inhibitors, especially in large amounts, can prevent treatment from working properly, so 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 ADVATE, contact your doctor immediately.

Children and adolescents

The warnings and precautions mentioned apply to both adults and children (aged 0 to 18 years).

Using ADVATE with other medicines

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy and lactation

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

Driving and using machines

Treatment with ADVATE has no influence on the ability to drive or operate machinery.

ADVATE contains sodium

This medicine contains 0.45 mmol of sodium (10 mg) per vial, which should be taken into consideration for patients on sodium-restricted diets.

3. How to use ADVATE

Treatment with ADVATE will be initiated by a physician experienced in the management of patients with haemophilia A.

Your doctor will calculate your dose of ADVATE (in international units or IU) based on your condition, body weight, and whether it is to be used for prevention or treatment of bleeding episodes. The frequency of administration will depend on how ADVATE acts in your body. Replacement therapy with ADVATE is usually a lifelong treatment.

Always follow exactly the administration instructions for this medicine given by your doctor. If in doubt, consult your doctor again.

Prevention of bleeding episodes

The usual dose of octocog alfa is 20 to 40 IU per kg of body weight, administered every 2 or 3 days. However, in some cases, especially in younger patients, more frequent administration or higher doses may be required.

Treatment of Bleeding Episodes

The dose of octocog alfa 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 episode.

Dose (IU) = body weight (kg) × desired increase in Factor VIII (% of normal) × 0.5

If you feel that the effect of ADVATE is insufficient, consult your doctor.

Your doctor will perform appropriate laboratory tests to ensure that you have adequate factor VIII levels. This is especially important if you are about to undergo major surgery.

Use in children and adolescents (aged 0 to 18 years)

For the treatment of bleeding episodes, the dose in children does not differ from that in adult patients. To prevent bleeding in children under 6 years of age, doses of 20 to 50 IU per kg of body weight administered 3 to 4 times per week are recommended. Administration of ADVATE in children (intravenously) does not differ from administration in adults. A central venous access device (CVAD) may be necessary to allow frequent infusions of factor VIII products.

How ADVATE is administered

ADVATE is normally administered intravenously by your doctor or nurse. You or another person may also administer the injection of ADVATE, but only after receiving proper training. Detailed instructions for administration are provided at the end of this leaflet.

If you use more ADVATE than you should

Follow exactly the administration instructions given by your doctor. If you have any doubts, consult your doctor. If you inject a higher dose of ADVATE than recommended, contact your doctor as soon as possible.

If you forget to use ADVATE

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

If you stop using ADVATE

Do not stop using ADVATE 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 experiences them.

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

• widespread rash, hives, and itching,
• swelling of the 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 early emergency treatment.

In children who have not previously received treatment with factor VIII-containing medicines, inhibitor antibodies may develop very frequently (in more than 1 in 10 patients); however, in patients who have previously received factor VIII treatment (more than 150 days of treatment), the risk is uncommon (less than 1 in 100 patients). If this occurs, the medicines you or your child are taking may no longer work properly, and you or your child may experience persistent bleeding. In this case, contact your doctor immediately.

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

Factor VIII inhibitors (in children who have not previously received treatment with factor VIII-containing medicines).

Common adverse effects (may affect up to 1 in 10 patients)

Headache and fever

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

Factor VIII inhibitors (in patients who have previously received factor VIII treatment [more than 150 days of treatment]), dizziness, flu-like symptoms, faintness, abnormal heartbeat, itchy red spots, chest discomfort, bruising at the injection site, reaction at the injection site, itching, increased sweating, unusual taste in the mouth, hot flushes, migraine, memory loss, chills, diarrhea, nausea, vomiting, difficulty breathing, sore throat, lymphatic vessel infection, pallor, eye inflammation, rashes, excessive sweating, swelling of feet and legs, decreased number of red blood cells, increased number of a type of white blood cells (monocytes), and pain in the upper abdomen or lower chest.

Related to surgery

Catheter-related infection, decreased number of red blood cells, swelling of limbs and joints, prolonged bleeding after drain removal, decreased factor VIII levels, and postoperative hematoma.

Related to central venous access devices (CVAD)

Catheter-related infection, systemic infection, and local blood clot at the catheter site.

Adverse effects with unknown frequency (cannot be estimated from available data)

Reactions that may be life-threatening (anaphylaxis) and other allergic reactions (hypersensitivity), general disorders (tiredness, lack of energy).

Additional adverse effects in children

In addition to the development of inhibitors in paediatric patients without prior treatment and complications associated with the catheter, clinical trials did not reveal any age-specific differences in adverse effects.

Reporting of adverse effects

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

5. Storage of ADVATE

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

Do not use this medicine after the expiry date stated on the packaging 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.

Until the expiry date, the blister containing the medicine may be stored at room temperature (up to 25 °C) for a single period not exceeding 6 months. In this case, this medicine expires at the end of this 6-month period or on the expiry date printed on the blister, whichever occurs first. Please note on the medicine packaging the end date of the 6-month room temperature storage period. The medicine must not be refrigerated again after being stored at room temperature.

Keep the medicine blister in the outer carton to protect it from light.

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

Use the medicine immediately after complete reconstitution of the powder.

Do not refrigerate the medicine after reconstitution.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging no longer required. This will help protect the environment.

6. Contents of the container and other information

Composition of ADVATE

• The active substance is octocog alfa (recombinant DNA-derived human coagulation factor VIII). Each vial of powder contains nominally 250, 500, 1000, 1500, 2000, or 3000 IU of octocog alfa.
• The other components are mannitol, sodium chloride, histidine, trehalose, calcium chloride, tromethamine, polysorbate 80, and glutathione (reduced).

Solvent vial: 5 ml of sterile water for injectable preparations.

Appearance of the product and contents of the pack

ADVATE is a white to off-white, friable powder.

After reconstitution, the solution is clear, colourless, and free from foreign particles.

Marketing Authorisation Holder

Takeda Manufacturing Austria AG
Industriestrasse 67
A-1221 Vienna
Tel: +800 66838470
E-mail: [email protected]

Manufacturers

Baxalta Belgium Manufacturing SA
Boulevard René Branquart 80
B-7860 Lessines
Belgium

Date of the most recent revision of this leaflet

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/.

Instructions for preparation and administration

ADVATE 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 ADVATE is administered.

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 preparation after reconstitution.

1. If the medicine is stored in the refrigerator, remove the sealed blister (containing powder vials and prefilled solvent syringe with 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 ADVATE packaging by removing the cap. Remove the BAXJECT III system from the blister.
4. Place ADVATE on a flat surface with the solvent vial on top (Fig. 1). The solvent vial has a blue stripe. Do not remove the blue protector until instructed later.
5. While holding the ADVATE with one hand in the BAXJECT III system, firmly press the solvent vial with the other hand until the system is fully compressed and the solvent flows into the ADVATE vial (Fig. 2). Do not tilt the system until the transfer is complete.
6. Confirm that the solvent transfer is complete. Gently swirl until all material is dissolved. Ensure that the ADVATE powder is completely dissolved; otherwise, the entire reconstituted solution may 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.

Injection Instructions

An aseptic technique must be used during administration.

A luer-lock syringe is required for administration.

Important note:

• Do not attempt to administer the injection unless you have received special training from your doctor or nurse.
• Inspect the prepared solution for particles or discoloration before administration (the solution should be clear, colourless, and free from foreign particles).

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

1. Remove the blue protector from the BAXJECT III system. Do not introduce air into the syringe. Connect the syringe to the BAXJECT III system.
2. Invert the system (with the vial containing the reconstituted solution on top). Draw the reconstituted solution into the syringe by slowly pulling back on the plunger.
3. Disconnect the syringe.
4. Attach a winged infusion needle to the syringe. Administer intravenously. The solution should be administered slowly at a rate determined by the patient's comfort level, not exceeding 10 ml per minute. Pulse should be monitored before and during administration of ADVATE. If a significant increase in pulse rate is observed, reduce the infusion rate or temporarily stop the infusion; this usually allows symptoms to resolve promptly (see section 4 "Possible side effects").
5. Dispose of any unused solution appropriately.

This information is intended for healthcare professionals only:

On-demand treatment

In the case of subsequent bleeding episodes, Factor VIII activity should not fall below the plasma activity level (expressed as % of normal or IU/dL) indicated for the corresponding period. The following table may be used as a guide for dosing in bleeding episodes and surgery.

The dose and frequency of administration should be adjusted according to the individual clinical response. Under certain circumstances (e.g., presence of low-titre inhibitors), doses higher than those calculated using the formula may be required.