Product Information for the User

IDELVION 250 UI, powder and solvent for injectable solution

IDELVION 500 UI, powder and solvent for injectable solution

IDELVION 1.000 UI, powder and solvent for injectable solution

IDELVION 2.000 UI, powder and solvent for injectable solution

IDELVION 3.500UI, powder and solvent for injectable solution

albutrepenonacog alfa (recombinant coagulation factor IX)

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

• Keep this product information, as you may need to read it again.

• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you should not give it to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

1. How to use IDELVION

1. Adverse effects
2. Storage of IDELVION

1. Contents of the package and additional information

What is IDELVION?

IDELVION is a medication for the treatment of hemophilia that replaces the natural factor IX of coagulation. The active ingredient of IDELVION is albutrepenonacog alfa (recombinant fusion protein that combines the coagulation factor IX with albumin [rIX-FP]).

The factor IX intervenes in blood coagulation. Patients with hemophilia B do not have this factor, which means that the blood does not clot as quickly as it should, resulting in a greater tendency to bleed. IDELVION acts by replacing the factor IX in patients with hemophilia B to enable their blood to clot.

How is IDELVION used?

IDELVION is used to prevent or stop bleeding caused by insufficient factor IX in patients of all ages with hemophilia B (also known ascongenital factor IX deficiencyorChristmas disease).

Do not use IDELVION

• If you are allergic to the active ingredient (albutrepenonacog alfa) or to any of the other components of this medication (listed in section 6).
• If you are allergic to hamster proteins.

Warnings and precautions

It is strongly recommended that each time you use IDELVION, you record the name and batch number of the product for tracking of the products and batches of the product that you have used.

Traceability

In order to improve the traceability of biological medications, the name and batch number of the administered medication must be clearly recorded.

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

• Allergic reactions (hypersensitivity) may occur. The product contains hamster protein residues (see also "Do not use IDELVION").If symptoms of allergic reactions appear, you must stop treatment immediately and contact your doctor or treatment center where you are being monitored. Your doctor must inform you of the first signs of hypersensitivity reactions.These include urticaria, generalized skin rash,chest pressure, difficulty breathing, low blood pressure (hypotension), and anaphylaxis (a severe allergic reaction that causes severe breathing difficulties or dizziness).

• Due to the risk of allergic reactions with factor IX, the initial administration of IDELVION must be performed under medical supervision to ensure access to adequate medical care in case of allergic reactions.

• The formation ofinhibitors(neutralizing antibodies) is a known complication of treatment with IDELVION. Inhibitors prevent the treatment from working correctly. If your bleeding is not controlled with IDELVION, inform your doctor immediately. You must be regularly monitored for the development of inhibitors.
• If you suffer from liver or heart disease or have recently undergone major surgery, please inform your doctor, as there is a higher risk of bleeding complications.
• If a central venous access device (DAVC) is required for the administration of IDELVION, your doctor will take into account the risk of complications related to the DAVC, such as local infections, blood infections (bacteremia), and the formation of a blood clot in the blood vessels (thrombosis) at the site of the catheter insertion.

Use of IDELVION with other medications

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

Driving and operating machines

IDELVION does not affect your ability to drive or operate machines.

IDELVION contains sodium

This medication contains up to 8.6mg of sodium (main component of table salt/for cooking) in each vial. This corresponds to 0.4% of the maximum daily sodium intake recommended for an adult.

Your treatment should be initiated and supervised by a doctor with experience in treating blood clotting disorders.Follow exactly the instructions of your doctor for the use of this medication. Consult with your doctor if you have any doubts.

Your doctor will calculate the dose of IDELVION you need. The amount of IDELVION you need and the duration of treatment depend on:

• the severity of your disease

• the location and intensity of the bleeding
• your clinical status and response to treatment
• your body weight

IDELVION is administered as an injection into a vein (intravenously, IV) after reconstitution of the powder with the solvent provided by your doctor or nurse. You or another person may also administer IDELVION as an intravenous injection, but only after receiving proper training.

If you use more IDELVION than you should

Immediately contact your doctor if you inject more IDELVION than your doctor has recommended.

If you interrupt treatment with IDELVION

Do not stop using IDELVION without consulting your doctor first.

Reconstitution and administration

General instructions

• The powder must be mixed with the solvent (liquid) and extracted from the vial while keeping the medication sterile (free of germs). Your doctor will show you how to prepare the solution and how to extract the solution from the vial correctly.
• IDELVION should not be mixed with other medications, 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 extracting or filtering the solution (see below) it should be visually inspected before use. Do not use the solution if it is 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 your doctor's instructions.

Reconstitution

Without opening any of the vials, warm the IDELVION powder and the solvent until they are at room temperature or body temperature. This can be done by leaving the vials at room temperature for about an hour or by 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 caps from the vials and, subsequently, clean the exposed parts of the rubber stoppers with an alcohol-soaked swab. Allow the vials to dry before opening the Mix2Vial package (which contains the transfer device with filter) and then follow the instructions below.

Transfer and administration

Use the venipuncture kit provided with the product and insert the needle into a vein. Allow the blood to flow to the end of the tube. Attach the syringe to the threaded stopcock of the venipuncture kit.Inject the reconstituted solution slowly (at a rate that feelscomfortable, up to a maximum of 5 ml/min) into the veinaccording to the instructions given by yourdoctor. Try not to let blood enter the syringe containing the product.

Check if you experience any adverse effects immediately after the injection. If you experience any adverse effect that may be related to the administration of IDELVION, the injection should be interrupted (see also sections 2 and 4).

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

Like all medications, this medication may produce adverse effects, although not all people will experience them.

Contact your doctor:

• if you notice symptoms of allergic reactions (see below);

• if you notice that the medication no longer works correctly.

The following adverse effects have been observed with factor IX medications:

• It is possible to experienceallergic hypersensitivity reactions(frequent) that include the following symptoms: erythema, generalized skin itching (urticaria), chest pressure, difficulty breathing, low blood pressure (hypotension), and anaphylaxis (a severe reaction that causes severe difficulty breathing and dizziness). If this happens, you must stop administering the medication immediately and contact your doctor.

• Inhibitors: the medication no longer works correctly (continuous bleeding). You may develop an inhibitor (neutralizing antibody) to factor IX (unknown frequency), which means that factor IX will no longer function correctly. If this happens, you must stop administering the medication immediately and contact your doctor.

The following adverse effects have been observedfrequently(may affect up to 1 in 10 people) with IDELVION:

• Headache

• Injection site reactions
• Dizziness
• Skin rash

The following adverse effects have been observedinfrequently(may affect up to 1 in 100 people):

• Eczema

Adverse effects in children and adolescents

It is expected that adverse effects in children will be the same as in 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 not listed in this prospectus. You can also report them directly through theSpanish System for Pharmacovigilance of Medicinal Products for Human Use: www.notificaRAM.es. 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.
• Do not store at a temperature above 25 °C.
• Do not freeze.
• Store the vial within its box to protect it from light.
• Once the product is reconstituted, it should be used preferably immediately.

If the reconstituted product is not administered immediately, the times and conditions of conservation before its use are the responsibility of the user.

Composition of IDELVION

The active principle is:

250 UI per vial; after reconstitution with 2.5 ml of water for injectable preparations, the solution contains 100 UI/ml of albutrepenonacog alfa.

500 UI per vial; after reconstitution with 2.5 ml of water for injectable preparations, the solution contains 200 UI/ml of albutrepenonacog alfa.

1,000 UI per vial; after reconstitution with 2.5 ml of water for injectable preparations, the solution contains 400 UI/ml of albutrepenonacog alfa.

2,000 UI per vial; after reconstitution with 5 ml of water for injectable preparations, the solution contains 400 UI/ml of albutrepenonacog alfa.

3,500 UI per vial; after reconstitution with 5 ml of water for injectable preparations, the solution contains 700 UI/ml of albutrepenonacog alfa.

The other components are:

Sodium citrate, polisorbate 80, mannitol, sucrose, and hydrochloric acid (for pH adjustment).

See the last paragraph of section 2.

Vehicle: water for injectable preparations

Appearance of IDELVION and contents of the package

IDELVION is presented as a yellowish to white powder and is supplied with a vehicle in the form of water for injectable preparations.

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

Presentation

A package containing 250, 500, or 1,000 UI that contains:

1 vial with powder

1 vial with 2.5 ml of water for injectable preparations

1 transfer device with filter 20/20

Administration equipment (inner box):

1 disposable 5 ml syringe

1 venipuncture device

2 alcohol-impregnated wipes

1 non-sterile dressing

A package containing 2,000 or 3,500 UI that contains:

1 vial with powder

1 vial with 5 ml of water for injectable preparations

1 transfer device with filter 20/20

Administration equipment (inner box):

1 disposable 10 ml syringe

1 venipuncture device

2 alcohol-impregnated wipes

1 non-sterile dressing

Only some package sizes may be marketed.

Marketing authorization holder and responsible manufacturer

CSL Behring GmbH

Emil-von-Behring-Straße 76

35041 Marburg

Germany

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

België/Belgique/BelgienLietuva

CSL Behring NVCentralPharma Communications UAB

Tel/Tel: +32 15 28 89 20Tel: +370 5 243 0444

Luxembourg/Luxemburg

CSL Behring NV

Tél/Tel: +32 15 28 89 20

Ceská republikaMagyarország

CSL Behring s.r.o.CSL Behring Kft.

Tel: + 420 702 137 233Tel.: +36 1 213 4290

DanmarkMalta

CSL BehringABAM Mangion Ltd.

Tlf: +46 8 544 966 70Tel: +356 2397 6333

DeutschlandNederland

CSL Behring GmbHCSL Behring BV

Tel:+49 6190 75 84810Tel: + 31 85 111 96 00

EestiNorge

CentralPharma Communications OÜ CSL Behring AB

Tel: +3726015540Tlf: +46 8 544 966 70

Ελλ?δαÖsterreich

CSL BehringΕΠΕCSL Behring GmbH

Τηλ: +30 210 7255 660Tel: +43 1 80101 1040

EspañaPolska

CSL Behring S.A.CSL Behring Sp.z o.o.

Tel: +34 933 67 1870Tel: +48 22 213 22 65

FrancePortugal

CSL Behring S.A.CSL Behring Lda

Tél: + 33–(0)-1 53 58 54 00Tel: +351 21 782 62 30

HrvatskaRomânia

Marti Farm d.o.o.Prisum Healthcare srl

Tel: +385 1 5588297Tel: +40 21 322 0171

IrelandSlovenija

CSL Behring GmbHEmmes Biopharma Global

Tel:+49 6190 75 84700s.r.o.-podružnica v Sloveniji

Tel: +386 41 42 0002

ÍslandSlovenská republika

CSL Behring ABCSL BehringSlovakias.r.o.

Sími: +46 8 544 966 70Tel: + 421 911 653 862

ItaliaSuomi/Finland

CSL Behring S.p.A.CSL Behring AB

Tel: +39 02 34964 200Puh/Tel: +46 8 544 966 70

Κ?προςSverige

CSL BehringΕΠΕCSL Behring AB

Τηλ: +30 210 7255 660Tel: +46 8 544 966 70

Latvija

CentralPharma Communications SIA

Tel: +371 6 7450947

Fecha de la última revisión de este prospecto 12/2024.

The information provided in this leaflet is available on the website of the European Medicines Agency:http://www.ema.europa.eu, and on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

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This information is intended solely for healthcare professionals:

Dosage

The dose and duration of treatment depend on the severity of the factor IX deficiency, the location and severity of the bleeding, and the patient's clinical status.

The number of factor IX units administered is expressed in International Units (UI), in relation to the current WHO standard for products containing factor IX. The plasma activity of factor IX is expressed as a percentage (in relation to normal human plasma) or in International Units (in relation to an international standard for plasma factor IX).

One International Unit (UI) of factor IX activity is equivalent to the amount of factor IX present in 1 ml of normal human plasma.

On-demand treatment

The calculation of the required dose of factor IX is based on the empirical finding that 1 UI of factor IX per kg of body weight increases plasma factor IX activity by 1.3 UI/dl (1.3% of normal activity) in patients ≥ 12 years and by 1.0 UI/dl (1.0% of normal activity) in patients <12 years.

Dose required (UI) = body weight (kg) x desired increase in factor IX (% of normal level or UI/dl) x {observed recovery reciprocal (UI/kg per UI/dl)}

Expected increase in factor IX (UI/dl or % of normal level) = dose (UI) x recovery (UI/dl per UI/kg)/body weight (kg)

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

Patients <12 years

In the case of incremental recovery of 1 UI/dl per 1 UI/kg, the dose is calculated as follows:

Dose required (UI) = body weight (kg) x desired increase in factor IX (UI/dl) x 1 dl/kg

Example:

1. A maximum level of 50% of the normal level is required in a 20 kg patient with severe hemophilia B. The appropriate dose would be 20 kg x 50 UI/dl x 1 dl/kg = 1,000 UI.

1. A dose of 1,000 UI of IDELVION, administered to a 25 kg patient, should cause a maximum increase in factor IX activity of 1,000 UI/25 kg x 1.0 (UI/dl per UI/kg) = 40 UI/dl (40% of normal level).

Patients ≥ 12 years of age

In the case of incremental recovery of 1.3 UI/dl per 1 UI/kg, the dose is calculated as follows:

Dose required (UI) = body weight (kg) x desired increase in factor IX (UI/dl) x 0.77 dl/kg

Example:

1. A maximum level of 50% of the normal level is required in an 80 kg patient with severe hemophilia B. The appropriate dose would be 80 kg x 50 UI/dl x 0.77 dl/kg = 3,080 UI.
2. A dose of 2,000 UI of IDELVION, administered to an 80 kg patient, should cause a maximum increase in factor IX activity of 2,000 UI x 1.3 (UI/dl per UI/kg)/80 kg = 32.5 UI/dl (32.5% of normal level).

In the case of the following bleeding events, the plasma factor IX activity should not be below the established plasma activity level (in % of normal level or in UI/dl) during the corresponding period. The following table can be used as a dosage guide for bleeding episodes and surgery:

Prophylactic treatment

For long-term prophylaxis to prevent bleeding in patients with severe hemophilia B, the usual dose is 35-50 UI/kg once a week. Well-controlled patients on a once-weekly regimen may be treated with up to 75 UI/kg every 10 or 14 days. In patients > 18 years, a longer interval between treatments may be considered.

In some cases, especially in young patients, it may be necessary to shorten the treatment intervals or use higher doses.

After a bleeding episode during prophylaxis, patients should maintain their prophylaxis regimen as much as possible, with the administration of 2 doses of IDELVION with a minimum of 24 hours between them, but longer if considered appropriate for the patient.

Pediatric population

In long-term prophylaxis, the recommended dosing regimen is 35-50 UI/kg once a week.For adolescents 12 years or older, the recommended dose is the same as for adults (see above).

Special warnings and precautions for use

Inhibitors

After repeated treatment with factor IX products, patients should be monitored for the development of neutralizing antibodies (inhibitors) that should be quantified in Bethesda Units (BU) using suitable biological tests.

Cases reported in the literature demonstrate a correlation between the appearance of a factor IX inhibitor and allergic reactions. Therefore, patients who experience allergic reactions should be evaluated to detect the presence of an inhibitor. It should be noted that patients with factor IX inhibitors may be at increased risk of anaphylaxis upon subsequent exposure to factor IX.

Monitoring of treatment

During treatment, it is recommended to adequately control factor IX levels to determine the dose to be administered and the frequency of infusions. Patient responses to factor IX may vary, demonstrating different half-lives and recoveries. The weight-based dose may need to be adjusted in patients with underweight or overweight. In the case of major surgery, it is essential to accurately monitor treatment substitution by coagulation tests (plasma factor IX activity).

When using a one-stage coagulation assay based on activated partial thromboplastin time (aPTT) in vitro to determine plasma factor IX activity in patient blood samples, the results of plasma factor IX activity may be significantly affected by the aPTT reagent and reference standard used in the assay. It is likely that measurement using a one-stage coagulation assay with a caolin-based aPTT reagent or an aPTT reagent with Actin FS will result in underestimation of the level of activity. This is particularly important when changing laboratories or reagents used in the assay.