Idelvion

Package leaflet: Information for the user

IDELVION 250 IU powder and solvent for solution for injection, 500 IU powder and solvent for solution for injection, 1,000 IU powder and solvent for solution for injection, 2,000 IU powder and solvent for solution for injection, 3,500 IU powder and solvent for solution for injection

albutrepenonacog alfa (recombinant coagulation factor IX)
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. 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 only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What IDELVION is and what it is used for

What is IDELVION?
IDELVION is a medicine for haemophilia that replaces the natural blood coagulation factor IX.
The active substance of IDELVION is albutrepenonacog alfa, a recombinant fusion protein consisting of coagulation factor IX fused with albumin (rIX-FP).
Factor IX is involved in blood clotting. Patients with haemophilia B have a deficiency of this factor, causing blood to not clot at the normal rate, which leads to a tendency to bleed. IDELVION works by replacing factor IX in patients with haemophilia B, enabling blood to clot properly.
What is IDELVION used for?
IDELVION is used to prevent or stop bleeding episodes caused by factor IX deficiency in patients of all age groups with haemophilia B (also known as congenital factor IX deficiency or Christmas disease).

2. What you should know before taking IDELVION

Do not take IDELVION

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

Warnings and precautions
It is strongly recommended that every time IDELVION is used, the product name and batch number are recorded to keep track of the products and batch numbers used.
Talk to your doctor, pharmacist, or nurse before taking IDELVION.

• Allergic-type hypersensitivity reactions may occur. The medicine contains traces of hamster proteins (see also “Do not take IDELVION”). If symptoms of allergic reactions occur, stop using the medicine immediately and contact your doctor or the treatment center where you are being followed. Your doctor will inform you about the early signs of hypersensitivity reactions. These include: hives, generalized rash, chest tightness, wheezing, low blood pressure (hypotension), and anaphylaxis (a severe allergic reaction causing serious breathing difficulties or dizziness).
• Due to the risk of allergic reactions with factor IX, the first administration of IDELVION must be performed under close medical supervision in case appropriate treatment for allergic reactions becomes necessary.
• The development of inhibitors (neutralizing antibodies) is a known complication that has been observed during treatment with IDELVION. Inhibitors prevent the treatment from working properly. If IDELVION is ineffective in controlling bleeding episodes, inform your doctor immediately. Regular monitoring for the possible development of inhibitors is required.
• If you have liver or heart disease or have recently undergone major surgery, please inform your doctor, as there is an increased risk of complications due to clot formation (coagulation).
• If a central venous access device (CVAD) is required for the injection of IDELVION, your doctor must consider the risk of complications including local infections, bacteria in the blood (bacteraemia), and formation of a blood clot in the blood vessel (thrombosis) at the site where the catheter is inserted.

Other medicines and IDELVION

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

Pregnancy and breastfeeding

• If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this medicine. During pregnancy and breastfeeding, IDELVION should be administered only if clearly necessary.

Driving and using machines
IDELVION does not affect the ability to drive vehicles or operate machinery.

IDELVION contains sodium
This medicine contains up to 8.6 mg of sodium (the main component of table salt) per vial. This corresponds to 0.4% of the maximum daily recommended sodium intake for an adult.

3. How to take IDELVION

Treatment must be initiated under the supervision of a physician experienced in the treatment of
coagulation disorders.
Always take this medicine exactly as instructed by your doctor. Check with your
physician if you are unsure.
Your doctor will determine the required dose of IDELVION. The amount of IDELVION needed and the duration of treatment depend on the following:

• severity of the disease
• location and severity of bleeding
• clinical condition and response
• body weight

IDELVION is administered by your doctor or nurse via intravenous (IV) injection after reconstitution of the powder with the solvent provided. You or another person may administer IDELVION via intravenous injection, but only after receiving adequate training.
If you have taken too much IDELVION
Inform your doctor immediately if you have injected more IDELVION than prescribed.
If you stop taking IDELVION
Do not stop taking IDELVION without consulting your doctor.
Reconstitution and administration
General instructions

• The powder must be mixed with the solvent (liquid) and withdrawn from the vial while maintaining sterility (germ-free). Your doctor will show you how to prepare the solution and how to correctly withdraw the solution from the vial.
• IDELVION must not be mixed with other medicines or solvents except those listed in section 6.
• The solution should be clear or slightly opalescent, yellow to colorless, and may show a slight shimmer when exposed to light but must not contain visible particles. After filtration/withdrawal (see below), the reconstituted solution should be inspected visually before administration. Do not use the solution if it is cloudy or contains deposits or particles.
• Unused medicine and waste materials resulting from this medicine must be disposed of in accordance with local regulations and the instructions of your doctor.

Reconstitution
Without opening the vials, bring the IDELVION powder and the solvent to room temperature or body temperature. This can be achieved by leaving the vials at room temperature for about one hour or by holding them in your hands for a few minutes.
DO NOT expose the vials to direct heat. The vials must not be heated above body temperature (37 °C).
Carefully remove the protective caps from the vials and clean the exposed rubber stoppers with an alcohol swab. Allow the vials to dry before opening the Mix2Vial package (containing the transfer device with filter), and then follow the instructions below.

1	1. Open the Mix2Vial by removing the cap. Do not remove the Mix2Vial from the blister pack!
2	2. Place the solvent vial on a flat and clean surface, holding the vial firmly. Take the Mix2Vial together with its entire packaging and push the terminal blue end directly into the stopper of the solvent vial.
3	3. Carefully remove the packaging from the Mix2Vial by holding the edge and pulling vertically upward. Make sure to remove only the blister packaging, not the Mix2Vial itself.
4	4. Place the IDELVION vial on a stable, flat surface. Invert the solvent vial with the attached Mix2Vial and push the tip of the transparent adapter downward through the stopper of the IDELVION vial. The solvent will automatically flow into the vial containing IDELVION.
5	5. With one hand, hold the IDELVION side of the Mix2Vial and with the other hand, hold the solvent side. Carefully unscrew counterclockwise to separate the device into two parts. Discard the solvent vial with the attached blue Mix2Vial adapter.
6	6. Gently rotate the IDELVION vial with the attached transparent adapter until the powder is completely dissolved. Do not shake.
7	7. Draw air into a sterile, empty syringe. Holding the IDELVION vial in an upright position, attach the syringe to the LuerLock connector of the Mix2Vial by screwing clockwise. Inject air into the IDELVION vial.

Withdrawal and administration

8	8. While pressing the syringe plunger, turn the device upside down and draw the solution into the syringe by slowly pulling back the plunger.
9	9. Now that the solution has been transferred into the syringe, firmly hold the syringe body (with the plunger facing downward) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing it counterclockwise.

Use the intravenous infusion device supplied with the product by inserting the needle into a vein.
Allow blood to flow back to the end of the tubing. Attach the syringe to the threaded closure end of the intravenous infusion device. Inject the reconstituted solution slowly (as comfortably as possible, up to a maximum of 5 mL/min) into the vein, following the instructions provided by your doctor.
Avoid allowing blood to enter the syringe containing the medicine.
Monitor for any immediate adverse reactions. If you notice the onset of adverse reactions that may be related to the administration of IDELVION, administration must be stopped (see also sections 2 and 4).
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Contact your doctor immediately:

• if you notice symptoms of allergic reactions (see below)
• if you notice that the medicine is no longer working properly

The following side effects have been observed with medicines containing factor IX:

• Allergic-type hypersensitivity reactions are possible (common) and may include the following symptoms: hives, skin rash (generalized urticaria), chest tightness, wheezing, low blood pressure (hypotension), and anaphylaxis (a serious allergic reaction causing severe breathing difficulties or dizziness). In such cases, stop using the medicine immediately and contact your doctor.
• Inhibitors: the medicine is no longer working effectively (ongoing bleeding). It is possible that an inhibitor (neutralizing antibody) against factor IX has developed (frequency not known), in which case factor IX is no longer effective. In these cases, stop using the medicine immediately and contact your doctor.

The following side effects have been observed commonly with IDELVION (may affect up to 1 in 10 people):

• Headache
• Reactions at the injection site
• Dizziness
• Rash

The following side effects have occurred uncommonly (may affect up to 1 in 100 people):

• Eczema

Side effects in children and adolescents
The side effects that may occur in children are the same as those in adults.
Reporting of side effects
If you notice any side effect, even if not listed in this leaflet, inform your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store IDELVION

• 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.
• Do not store above 25 °C.
• Do not freeze.
• Keep the vial in the outer packaging to protect it from light.
• The reconstituted medicine should preferably be used immediately.
• If the reconstituted medicine is not administered immediately, the times and conditions of storage prior to use are under the responsibility of the user.

6. Package contents and other information

What IDELVION contains
The active substance is:
250 IU per vial; after reconstitution with 2.5 mL of water for injections, the solution contains 100 IU/mL of albutrepenonacog alfa.
500 IU per vial; after reconstitution with 2.5 mL of water for injections, the solution contains 200 IU/mL of albutrepenonacog alfa.
1,000 IU per vial; after reconstitution with 2.5 mL of water for injections, the solution contains 400 IU/mL of albutrepenonacog alfa.
2,000 IU per vial; after reconstitution with 5 mL of water for injections, the solution contains 400 IU/mL of albutrepenonacog alfa.
3,500 IU per vial; after reconstitution with 5 mL of water for injections, the solution contains 700 IU/mL of albutrepenonacog alfa.

The other components are:
Sodium citrate, Polysorbate 80, Mannitol, Sucrose, hydrochloric acid (for pH adjustment).
See the last paragraph of section 2.
Solvent: Water for injections

What IDELVION looks like and contents of the pack
IDELVION is a pale yellow to white powder supplied with water for injections as solvent.
The reconstituted solution is from clear to slightly opalescent, yellow to colourless, and may appear luminous when viewed against the light, but must not contain visible particles.

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

• 1 vial of powder
• 1 vial containing 2.5 mL of water for injections
• 1 transfer device with 20/20 filter

An inner carton containing:

• 1 single-use 5 mL syringe
• 1 intravenous administration set
• 2 alcohol swabs
• 1 non-sterile adhesive plaster

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

• 1 vial of powder
• 1 vial containing 5 mL of water for injections
• 1 transfer device with 20/20 filter

An inner carton containing:

• 1 single-use 10 mL syringe
• 1 intravenous administration set
• 2 alcohol swabs
• 1 non-sterile adhesive plaster

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Straße 76
35041 Marburg
Germany

For any information about this medicinal product, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
CSL Behring NV CentralPharma Communications UAB
Tél/Tel: +32 15 28 89 20 Tel: +370 5 243 0444

България Luxembourg/Luxemburg
МагнаФарм България ЕАД CSL Behring NV
Тел: +359 2 810 3949 Tél/Tel: +32 15 28 89 20

Česká republika Magyarország
CSL Behring s.r.o. CSL Behring Kft.
Tel: + 420 702 137 233 Tel.: +36 1 213 4290

Danmark Malta
CSL Behring AB AM Mangion Ltd.
Tel: +46 8 544 966 70 Tel: +356 2397 6333

Deutschland Nederland
CSL Behring GmbH CSL Behring BV
Tel: +49 69 30584437 Tel: + 31 85 111 96 00

Eesti Norge
CentralPharma Communications OÜ CSL Behring AB
Tel: +3726015540 Tlf: +46 8 544 966 70

Ελλάδα Österreich
CSL Behring ΕΠΕ CSL Behring GmbH
Τηλ: +30 210 7255 660 Tel: +43 1 80101 2463

España Polska
CSL Behring S.A. CSL Behring Sp.z o.o.
Tel: +34 933 67 1870 Tel: +48 22 213 22 65

France Portugal
CSL Behring S.A. CSL Behring Lda
Tél: + 33 –(0)-1 53 58 54 00 Tel: +351 21 782 62 30

Hrvatska România
Marti Farm d.o.o. Prisum Healthcare srl
Tel: +385 1 5588297 Tel: +40 21 322 0171

Ireland Slovenija
CSL Behring GmbH Emmes Biopharma Global s.r.o.-podružnica v
Tel: +49 69 30517254 Sloveniji
Tel:+ 386 41 42 0002

Ísland Slovenská republika
CSL Behring AB CSL Behring s.r.o.
Sími: +46 8 544 966 70 Tel: + 421 911 653 862

Italia Suomi/Finland
CSL Behring S.p.A. CSL Behring AB
Tel: +39 02 34964 200 Puh/Tel: +46 8 544 966 70

Κύπρος Sverige
CSL Behring ΕΠΕ CSL Behring AB
Τηλ: +30 210 7255 660 Tel: +46 8 544 966 70

Latvija United Kingdom (Northern Ireland)
CentralPharma Communications SIA CSL Behring GmbH
Tel: +371 6 7450497 Tel: +49 69 305 17254

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

The following information is intended exclusively for healthcare professionals:

Dosage
The dose and duration of replacement therapy depend on the severity of factor IX deficiency, the
site and extent of bleeding, and the clinical condition of the patient.
The number of units of factor IX administered is expressed in International Units (IU) relative to
the current WHO standard for factor IX-containing products. Plasma factor IX activity is expressed
as a percentage (relative to normal human plasma) or in International Units (based on an international standard for factor IX in plasma).
One International Unit (IU) of factor IX corresponds to the amount of factor IX contained in 1 mL of
normal human plasma.

Treatment on-demand (as needed)
The calculation of the required dose of factor IX is based on the empirical observation that 1 IU of factor IX per kg of body weight increases plasma factor IX activity by approximately 1.3 IU/dL (1.3% of normal activity) in patients aged 12 years and older, and by approximately 1.0 IU/dL (1.0% of normal activity) in patients under 12 years of age. The required dose is determined using the following formula:
Required dose (IU) = body weight (kg) × desired increase in factor IX (% of normal or IU/dL) × {reciprocal of observed recovery (IU/kg per IU/dL)}
Expected increase in factor IX (IU/dL or % of normal) = dose (IU) × recovery (IU/dL per IU/kg) / body weight (kg)
The amount and frequency of administration should always be guided by clinical efficacy in the individual case.

Patients under 12 years of age
For an incremental recovery of 1 IU/dL per 1 IU/kg, the dose is calculated as follows:
Required dose (IU) = body weight (kg) × desired increase in factor IX (IU/dL) × 1 dL/kg

Example

1. A level of 50% of normal is required in a 20 kg patient with severe haemophilia B. The appropriate dose would be 20 kg × 50 IU/dL × 1 dL/kg = 1,000 IU.
2. A dose of 1,000 IU of IDELVION administered to a 25 kg patient is expected to result in a post-infusion factor IX level of 1,000 IU / 25 kg × 1.0 (IU/dL per IU/kg) = 40 IU/dL (40% of normal).

Patients aged 12 years and older
For an incremental recovery of 1.3 IU/dL per 1 IU/kg, the dose is calculated as follows:
Required dose (IU) = body weight (kg) × desired increase in factor IX (IU/dL) × 0.77 dL/kg

Example

3. A level of 50% of normal is required in an 80 kg patient with severe haemophilia B. The appropriate dose would be 80 kg × 50 IU/dL × 0.77 dL/kg = 3,080 IU.
4. A dose of 2,000 IU of IDELVION administered to an 80 kg patient is expected to result in a peak post-infusion factor IX level of 2,000 IU × 1.3 (IU/dL per IU/kg) / 80 kg = 32.5 IU/dL (32.5% of normal).

In the event of any of the following bleeding episodes, factor IX activity should not fall below a specified plasma activity level (as a percentage of normal or IU/dL) during the corresponding period. The table below may be used as a guide for dosage in cases of bleeding and surgical intervention:

Prophylaxis
In patients with severe haemophilia B, the usual dose for long-term prophylaxis of bleeding
episodes is 35–50 IU/kg once weekly.
Some patients who show optimal disease control with a once-weekly dosing regimen may switch to a dose of up to 75 IU/kg administered at intervals of 10 or 14 days. For patients older than 18 years, further extension of the dosing interval may be considered (see section 5.1).
In some cases, particularly in younger patients, shorter intervals or higher doses may be required.
Following a bleeding episode during prophylaxis, patients should strictly adhere to their prophylactic regimen, with 2 doses of IDELVION administered at least 24 hours apart or with a longer interval, if considered appropriate for the patient.

Paediatric population
For long-term prophylaxis, the recommended dosing regimen is 35–50 IU/kg once weekly. For adolescents aged 12 years and older, dosing recommendations are the same as for adults (see above).

Special warnings and precautions for use

Inhibitors
After repeated administrations of medicinal products containing human coagulation factor IX, patients should be monitored for the development of neutralising antibodies (inhibitors), which should be quantified in Bethesda Units (BU) using appropriate biological assays.
Cases have been reported in the literature showing a correlation between the appearance of factor IX inhibitors and allergic reactions. Therefore, patients experiencing allergic reactions should be tested for the presence of inhibitors. It should be emphasized that patients with factor IX inhibitors may be at increased risk of anaphylaxis following subsequent administrations of factor IX.

Monitoring of treatment
During treatment, appropriate monitoring of factor IX levels is recommended to determine the required dose and frequency of infusions. Individual patients may show variable responses to factor IX, indicating differences in half-life and recovery. Dose calculations based on body weight may require adjustment in underweight or overweight patients.
Particularly during major surgical procedures, careful monitoring of replacement therapy through coagulation assays (plasma factor IX activity) is essential.
When using a one-stage in vitro coagulation assay based on activated partial thromboplastin time (aPTT) to determine factor IX activity in patient blood samples, the results of plasma factor IX activity may be significantly influenced by both the type of aPTT reagent and the reference standard used in the assay. Measurement with a one-stage coagulation assay using a kaolin-based aPTT reagent or an Actin FS-based aPTT reagent will likely result in an underestimation of the activity level. This is particularly important when changing laboratories and/or reagents used in the assay.
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