Product Information for the User

AFSTYLA 250 UI, powder and solvent for injectable solution

AFSTYLA 500 UI, powder and solvent for injectable solution

AFSTYLA 1.000 UI, powder and solvent for injectable solution

AFSTYLA 1.500 UI, powder and solvent for injectable solution

AFSTYLA 2.000 UI, powder and solvent for injectable solution

AFSTYLA 2.500 UI, powder and solvent for injectable solution

AFSTYLA 3.000 UI, powder and solvent for injectable solution

recombinant single-chain coagulation factor VIII (antihemophilic factor, octocog alfa)

Read this leaflet carefully before you or your child 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, pharmacist or nurse.
• This medicine has been prescribed for you or your child only, and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

AFSTYLA is a product with human coagulation factor VIII that is produced using recombinant DNA technology. The active ingredient of AFSTYLA is lonoctocog alfa.

AFSTYLA is used to treat and prevent bleeding episodes in patients with hemophilia A (congenital deficiency of factor VIII). Factor VIII is a protein necessary for blood coagulation. Patients with hemophilia A lack this factor, which causes their blood to clot more slowly than it should, resulting in a higher tendency to bleed. AFSTYLA acts by replacing the absent factor VIII in patients with hemophilia A, allowing their blood to clot normally.

AFSTYLA can be used in all age groups.

Do not use AFSTYLA

• If the patient has experienced a potentially life-threatening allergic reaction to AFSTYLA or any of its components (listed in section 6).including those listed in section 6.
• If the patient is allergic to hamster proteins.

Warnings and precautions

Traceability

It is essential to keep a record of the AFSTYLA batch number.

Therefore, each time you use a new AFSTYLA package, note the date and batch number (which is on the box after “Batch”) and store this information in a safe place.

Consult your doctor, pharmacist, or nurse before starting to use AFSTYLA.

• Allergic reactions (hypersensitivity) may occur. The product contains hamster protein residues (see also "Do not use AFSTYLA").If allergy symptoms appear, stop treatment immediately and contact your doctor.Your doctor should inform you of thefirst signs of allergic reactions. These include hives, generalized skin rash, chest pressure, difficulty breathing, low blood pressure, and anaphylaxis (a severe allergic reaction that causes severe breathing difficulties and dizziness).
• The formation ofinhibitors(antibodies) is a known complication that may occur during treatment with all factor VIII composite medications. These inhibitors, especially in large quantities, prevent the treatment from working correctly. You or your child will be closely monitored for the development of inhibitors. If your bleeding or your child's bleeding is not being controlled with AFSTYLA, consult your doctor immediately.
• If you have been told that you or your child have a heart condition or are at risk of developing one, inform your doctor or pharmacist.
• If a central venous access device (CVD) is used for AFSTYLA injection, your doctor should consider and discuss with you the risk of complications, such as local infections, bloodstream infections (bacteremia), and the formation of blood clots (thrombosis) in the blood vessels at the insertion site.

Other medications and AFSTYLA

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, think you may be pregnant, or intend to become pregnant, consult your doctor or pharmacist before using this medication.
• During pregnancy and breastfeeding, AFSTYLA should only be administered if clearly necessary.

Driving and operating machinery

AFSTYLA does not affect your ability to drive or operate machinery.

AFSTYLA contains sodium

This medication contains 35 mg of sodium (main component of table salt/for cooking) in each vial. This is equivalent to 1.8% of the maximum daily sodium intake recommended for an adult.

Your treatment should be supervised by a doctor with experience in treating blood clotting disorders.

Follow exactly the administration instructions for this medication as indicated by your doctor. In case of doubt, consult your doctor again.

Dose

The amount of AFSTYLA that you or your child need and the duration of treatment depend on:

• the severity of your illness
• the location and intensity of the bleeding
• your clinical condition and response to treatment
• your body weight

Follow the instructions indicated by your doctor.

Reconstitution and administration

General instructions

• The powder must be mixed with the solvent (liquid) and extracted from the vial in aseptic conditions.
• AFSTYLA should not be mixed with other medications or solvents, except those mentioned in section 6.
• The solution must be transparent or slightly opalescent, between yellow and colorless, that is, it may shine when exposed to light but should not contain any visible particles. After filtering or extracting the solution (see below) it must be rechecked before use. Do not use the solution if it is visibly turbid or contains flakes or particles.
• The disposal of unused product and all residual materials will be carried out in accordance with local regulations and the doctor's instructions.

Reconstitution and administration

Without opening any of the vials, make sure that the AFSTYLA powder and the liquid are at room temperature or body temperature. This can be done by leaving the vials at room temperature for about an hour or holding them in your hands for a few minutes. Do not expose the vials to direct heat. The vials should not be heated above body temperature (37 °C).

Carefully remove the protective capsules from the vials and, subsequently, clean the exposed part of the rubber stoppers with an alcohol-soaked swab. Allow the vials to dry before opening the Mix2Vial package (which contains the transfer filter) and, subsequently, follow the instructions indicated below.

Use the provided venipuncture kit and insert the needle into a vein. Allow the blood to flow to the end of the tube. Attach the syringe to the threaded blocking end of the venipuncture kit.Inject the reconstituted solution slowly (at a rate that feels comfortable to you, up to a maximum of 10 ml/min) into the veinaccording to the instructions given by your doctor. Try not to let blood enter the syringe containing the product.

Check if you experience any adverse effects immediately after injection. If you experience any adverse effect that may be related to the administration of AFSTYLA, the injection must be interrupted (see also section 2).

Use in children and adolescents

AFSTYLA can be used in children and adolescents of all ages. In the case of children under 12 years, higher doses or more frequent injections may be needed. In children over 12 years, the same dose as in adults can be used.

If you use more AFSTYLA than you should

If more AFSTYLA than prescribed has been injected, inform your doctor.

If you forgot to use AFSTYLA

Do not administer a double dose to compensate for the missed dose. Administer the next dose immediately and follow your doctor's instructions.

If you interrupt treatment with AFSTYLA

If you interrupt the use of AFSTYLA, you may no longer be protected against bleeding or you may not stop bleeding if you are currently bleeding. Do not stop using AFSTYLA without consulting your doctor first.

If you have any other questions about the use of this medication, ask your doctor, pharmacist, or nurse.

Like all medications, AFSTYLA may cause adverse effects, although not everyone will experience them.

Stop using the medication immediately and contact your doctor:

• if you notice symptoms of allergic reactions
• It is possible that you may experienceallergic reactionsthat include the following symptoms: hives, generalized urticaria (itchy rash), chest tightness, wheezing, low blood pressure, and anaphylaxis (severe reaction that causes severe difficulty breathing or dizziness). If this happens, you must stop the medication immediately and contact your doctor.
• if you notice that the medication has stopped working correctly(bleeding does not stop) For children who have not been previously treated with factor VIII medications, inhibitors (see section 2) may form frequently (more than 1 in 10 patients); however, in patients who have received previous treatment with factor VIII (more than 150 days of treatment) the risk is uncommon (less than 1 in 100 patients). If you or your child has developed an inhibitor due to the medication, you may experience persistent bleeding. If this happens, you must contact your doctor immediately.

Frequent Adverse Effects (may affect up to 1 in 10 people)

• Tickling or numbness (paresthesia).
• Skin rash.
• Fever.

Uncommon Adverse Effects (may affect up to 1 in 100 people)

• Itching.
• Skin redness.
• Pain at the injection site.
• Chills.
• Sensation of heat.

Adverse Effects in Children and Adolescents

No specific age-related differences in adverse reactions have been observed between children, adolescents, and adults.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the national notification system included in theAppendix V. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

• 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 in the box.
• Store in the refrigerator (between 2 °C and 8 °C).
• Before reconstituting the AFSTYLA powder, it can be stored at room temperature (below 25 °C) for a single period not exceeding 3 months, within the expiration date printed on the boxes and vials. Note the date when you begin to store AFSTYLA at room temperature on the medication box.
• Once the medication has been removed from the refrigerator, it should not be put back in the same one.
• Do not freeze.
• Store the vial within its box to protect it from light.
• Once the medication has been reconstituted, it should be used preferably immediately.
• If the reconstituted product is not administered immediately, the storage times and conditions before use are the responsibility of the user.

Composition of AFSTYLA

The active ingredient is:

250 IU per vial; after reconstitution with 2.5 ml of water for injection, the solution contains 100 IU/ml of lonoctocog alfa.

500 IU per vial; after reconstitution with 2.5 ml of water for injection, the solution contains 200 IU/ml of lonoctocog alfa.

1,000 IU per vial; after reconstitution with 2.5 ml of water for injection, the solution contains 400 IU/ml of lonoctocog alfa.

1,500 IU per vial; after reconstitution with 5 ml of water for injection, the solution contains 300 IU/ml of lonoctocog alfa.

2,000 IU per vial; after reconstitution with 5 ml of water for injection, the solution contains 400 IU/ml of lonoctocog alfa.

2,500 IU per vial; after reconstitution with 5 ml of water for injection, the solution contains 500 IU/ml of lonoctocog alfa.

3,000 IU per vial; after reconstitution with 5 ml of water for injection, the solution contains 600 IU/ml of lonoctocog alfa.

The other components are:

L-histidine, polisorbate 80, calcium chloride dihydrate, sodium chloride (see the last section of section 2), sucrose.

Vehicle: water for injection.

Appearance of AFSTYLA and contents of the pack

AFSTYLA is presented as a powder or friable mass of white or slightly yellowish color and a transparent and colorless solution for injection.

The reconstituted solution should be transparent or slightly opalescent, between yellow and colorless, i.e. it may shine when exposed to light but should not contain any visible particles.

Presentation

A pack containing 250, 500 or 1,000 IU includes:

1 vial with powder

1 vial with 2.5 ml of water for injection

1 transfer device with filter 20/20

An inner box containing:

1 disposable 5 ml syringe

1 venipuncture set

2 alcohol-impregnated swabs

1 non-sterile dressing

A pack containing 1,500, 2,000, 2,500 or 3,000 IU includes:

1 vial with powder

1 vial with 5 ml of water for injection

1 transfer device with filter 20/20

An inner box containing:

1 disposable 10 ml syringe

1 venipuncture set

2 alcohol-impregnated swabs

1 non-sterile dressing

Only some pack sizes may be marketed.

Primary packaging

250 IU Glass vial with rubber stopper, orange plastic disk and green striped aluminium cap

500 IU Glass vial with rubber stopper, blue plastic disk and green striped aluminium cap

1,000 IU Glass vial with rubber stopper, green plastic disk and green striped aluminium cap

1,500 IU Glass vial with rubber stopper, turquoise plastic disk and green striped aluminium cap

2,000 IU Glass vial with rubber stopper, purple plastic disk and green striped aluminium cap

2,500 IU Glass vial with rubber stopper, light grey plastic disk and green striped aluminium cap

3,000 IU Glass vial with rubber stopper, yellow plastic disk and green striped aluminium cap

Marketing authorisation holder and manufacturer

CSL Behring GmbH

Emil-von-Behring-Straße 76

35041 Marburg

Germany

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

Date of the last revision of this leaflet: {12/2024}.

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

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This information is intended solely for healthcare professionals:

Monitoring of treatment

During the course of treatment, it is recommended to control the factor VIII levels adequately to determine the dose to be administered and the frequency of injections. The responses of patients to factor VIII may vary, which demonstrates that they have different half-lives and recoveries. The dose based on body weight may need to be adjusted in patients with insufficient or excessive weight. In the case of major surgery, it is essential to control the substitution therapy precisely by analyzing coagulation (factor VIII plasma activity).

When using a one-stage coagulation assay based on the activated partial thromboplastin time (aPTT) in vitro to determine factor VIII activity in patient blood samples, the results of factor VIII plasma activity may be significantly affected by both the type of aPTT reagent and the reference standard used in the assay. Significant discrepancies may also occur between the results obtained in the one-stage coagulation assay based on aPTT and those obtained in the chromogenic substrate assay according to the European Pharmacopoeia. This is particularly important when changing the laboratory or reagents used in the assay.

Factor VIII plasma activity in patients receiving AFSTYLA should be monitored using a chromogenic substrate assay or a one-stage coagulation assay to guide the dose administered and the frequency of repeated injections. The result of the chromogenic substrate assay more accurately reflects the clinical hemostatic potential of AFSTYLA, so it is the preferred method. The result of the one-stage coagulation assay underestimates the level of factor VIII activity compared to the result of the chromogenic substrate assay by approximately 45%. If a one-stage coagulation assay is used, the result should be multiplied by a conversion factor of 2 to determine the patient's factor VIII activity level.

Dosage

The dose and duration of substitution therapy depend on the severity of factor VIII deficiency, the location and extent of the hemorrhage, and the patient's clinical status.

The number of factor VIII units administered is expressed in International Units (IU), which correspond to the current World Health Organization (WHO) standard for factor VIII concentrates. Factor VIII activity in plasma is expressed as a percentage (in relation to normal human plasma) or, preferably, in International Units (in relation to an international standard for factor VIII in plasma).

One International Unit (IU) of factor VIII activity corresponds to the amount of factor VIII present in 1 ml of normal human plasma.

The potency assignment is determined by a chromogenic substrate assay.

Factor VIII plasma levels can be monitored using a chromogenic substrate assay or a one-stage coagulation assay.

On-demand treatment

The calculation of the required dose of factor VIII is based on the empirical finding that 1 International Unit (IU) of factor VIII per kg of body weight increases plasma factor VIII activity by 2 IU/dl.

The required dose is determined using the following formula: Dose (IU) = body weight (kg) x desired increase in factor VIII (IU/dl or % of normal level) x 0.5 (IU/kg per IU/dl)

The dose and frequency of administration will be established based on the observed clinical efficacy in each case.

In the case of the following hemorrhagic events, factor VIII activity should not be less than the established plasma activity level (in % of normal level or IU/dl) during the corresponding period. The following table may be used as a guide for dosing in hemorrhagic events and surgery:

Prophylactic treatment

The recommended initial treatment regimen is 20 to 50 IU/kg of AFSTYLA administered 2 or 3 times a week. The regimen may be adjusted based on the patient's response.

Pediatric population

The recommended initial treatment regimen in children (0 to <12 years)

In adolescents aged 12 years or older, the recommended doses are the same as those for adults.

Geriatric population

AFSTYLA has not been studied in patients aged 65 years or older.