Advate 250 IU powder and solvent for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the user

ADVATE 250UI powder and solvent for solution for injection

ADVATE 500UI powder and solvent for solution for injection

ADVATE 1000UI powder and solvent for solution for injection

ADVATE 1500UI powder and solvent for solution for injection

Octocog alfa (recombinant human coagulation factor VIII)

Read all of 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 questions, ask 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 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 this leaflet:

1. What ADVATE is and what it is used for
2. What you need to know before using 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 ingredients 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 low risk that you may experience an anaphylactic reaction (a sudden, severe allergic reaction) to ADVATE. You should be aware that early signs of an allergic reaction include rash, itching, hives, generalized itching, swelling of the lips and tongue, difficulty breathing, wheezing, chest tightness, general malaise, 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 when present in high amounts, can prevent the treatment from working properly. You and your child will therefore be closely monitored for the development of such inhibitors. If your bleeding or your child's bleeding is not being 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).

Use of 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 might be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

Driving and use of 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.

Incorrect administration of ADVATE

Incorrect administration (injection into an artery or outside the vein) should be avoided, as it may cause mild, short-term reactions at the injection site, such as bruising and redness.

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 prophylaxis or for the 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.

Follow exactly the administration instructions for this medicine provided by your doctor. If in doubt, consult your doctor again.

Prevention of bleeding

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 injections 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.

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 undergoing major surgery.

Use in children and adolescents (0 to 18 years of age)

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 body weight 3 to 4 times per week are recommended. Administration of ADVATE in children (intravenous) does not differ from administration in adults. A central venous access device (CVAD) may be necessary to allow frequent infusions of factor VIII products.

Due to the reduced injection volume of reconstituted ADVATE to 2 ml, the time available to react to hypersensitivity reactions during injection is further reduced. Therefore, caution is advised when injecting reconstituted ADVATE at 2 ml, especially in children.

How ADVATE is administered

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

If you use more ADVATE than you should

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

If you forget to use ADVATE

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 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 will experience 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:

• generalized rash, hives, 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) syncope require early emergency treatment.

In children who have not previously received treatment with factor VIII-containing medicines, inhibitory antibodies may occur very frequently (more than 1 in every 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 every 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 such a 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, fainting, abnormal heartbeat, itchy red spots, chest discomfort, bruising at injection site, reaction at injection site, itching, increased sweating, unusual taste in mouth, hot flushes, migraines, 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, increase in 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 (fatigue, lack of energy).

Additional adverse effects in children

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

Reporting of adverse effects

If you experience any 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 detailed 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 record 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 dissolution 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 that you no longer need. This will help protect the environment.

6. Contents of the container and additional 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, or 1500 IU of octocog alfa.
• The other components are mannitol, sodium chloride, histidine, trehalose, calcium chloride, trometamol, polysorbate 80, and glutathione (reduced).

Solvent vial: 2 ml of sterile water for injection

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 Authorization 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 review of this summary

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 medicines 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 has been 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 mark. Do not remove the blue protector until instructed later.
5. While holding the BAXJECT III system firmly in one hand, press down firmly with the other hand on the solvent vial 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. Ensure that the transfer of solvent is complete. Gently swirl until all material is dissolved. Make sure that the ADVATE powder is completely dissolved; otherwise, 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.

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, colorless, and free of foreign particles).

Do not use ADVATE if the solution is not completely clear or not fully 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 the plunger.
3. Disconnect the syringe.
4. Attach a winged infusion needle to the syringe. Administer intravenously. The solution should be given slowly at a rate determined by the patient's level of comfort, 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 interrupt the injection; this usually allows symptoms to resolve promptly (see section 4 "Possible adverse 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. In certain circumstances (e.g., presence of low-titer inhibitors), doses higher than those calculated by the formula may be required.