Idelvion 2000 IU powder and solvent for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

IDELVION 250 IU, powder and solvent for solution for injection

IDELVION 500 IU, powder and solvent for solution for injection

IDELVION 1,000 IU, powder and solvent for solution for injection

IDELVION 2,000 IU, powder and solvent for solution for injection

IDELVION 3,500 IU, powder and solvent for solution for injection

albutrepenonacog alfa (recombinant coagulation factor IX)

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, ask your doctor, pharmacist or nurse.

• This medicine has been prescribed for you only, and you must not give it to other people, even if they have the same symptoms as you, because it may harm them.

• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are possible adverse effects not listed in this leaflet. See section 4.

Leaflet contents:

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 used to treat haemophilia by replacing the body’s natural blood clotting factor IX. The active substance in IDELVION is albutrepenonacog alfa (recombinant factor IX albumin fusion protein [rIX-FP]).

Factor IX plays a role in blood coagulation. Patients with haemophilia B lack this factor, meaning their blood does not clot as quickly as it should, resulting in a tendency to bleed. IDELVION works by replacing factor IX in patients with haemophilia B, enabling their blood to clot properly.

What is IDELVION used for?

IDELVION is used to prevent or control bleeding in patients of all ages with haemophilia B due to a lack of sufficient factor IX (also known as congenital factor IX deficiency or Christmas disease).

2. What you need to know before using IDELVION

Do not use IDELVION

• if you are allergic to the active substance (albutrepenonacog alfa) or to any of the other components of this medicine (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 product name and batch number to keep track of the products and batches you have used.

Traceability

In order to improve traceability of biological medicines, the name and batch number of the administered medicine should be clearly documented.

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

• Allergic reactions (hypersensitivity) may occur. The product contains traces of hamster proteins (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 should inform you about the early signs of hypersensitivity reactions. These include hives, widespread rash, tightness in the chest, difficulty breathing, low blood pressure (hypotension), and anaphylaxis (a severe allergic reaction causing serious breathing problems or dizziness).

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

• The development of inhibitors (neutralizing antibodies) is a known complication reported during treatment with IDELVION. Inhibitors prevent the treatment from working properly. If bleeding is not controlled with IDELVION, inform your doctor immediately. You should be regularly monitored for the development of inhibitors.

• If you have liver or heart disease or have recently undergone major surgery, please inform your doctor, as there is an increased risk of blood clotting complications.

• If a central venous access device (CVAD) is required for the administration of IDELVION, your doctor will consider the risk of CVAD-related complications, such as local infections, bacteria in the blood (bacteremia), and formation of a blood clot in blood vessels (thrombosis) at the catheter insertion site.

Use of IDELVION with other medicines

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

Pregnancy and breastfeeding

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

Driving and using machines

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

IDELVION contains sodium

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

3. How to use IDELVION

Your treatment must be initiated and supervised by a physician experienced in the treatment of blood coagulation disorders. Always follow your doctor's instructions exactly for using this medicine. Consult your doctor if you have any doubts.

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

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

IDELVION is administered as an intravenous (IV) injection after reconstituting 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 appropriate training.

If you use more IDELVION than you should

Contact your doctor immediately if you inject more IDELVION than prescribed.

If you stop treatment with IDELVION

Do not stop using IDELVION without first 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 mentioned in section 6.
• The solution should be transparent or slightly opalescent, yellow to colorless; that is, it may shimmer when exposed to light but must not contain any visible particles. After withdrawing or filtering the solution (see below), it should be visually inspected before use. Do not use the solution if it is cloudy or contains flakes or particles.
• Disposal of unused product and all residual materials must be carried out in accordance with local regulations and your doctor's instructions.

Reconstitution

Without opening any vials, warm the IDELVION powder and the solvent to room temperature or body temperature. This can be achieved by leaving the vials at room temperature for approximately one hour or by holding them in your hands for several 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, then clean the exposed portion of the rubber stoppers with an alcohol-impregnated wipe. Allow the vials to dry before opening the Mix2Vial package (which contains the transfer device with filter), and then follow the instructions outlined below.

1	Open the container holding the Mix2Vial by removing the seal. Do not remove the Mix2Vial from the blister pack.
2	Place the solvent vial on a clean, flat surface and hold it firmly. Hold the Mix2Vial together with the blister pack and push the blue end downward until it engages into the stopper of the solvent vial.
3	Carefully remove the blister pack from the Mix2Vial by holding the edge and pulling vertically upward. Make sure you remove only the blister pack and not the Mix2Vial.
4	Place the IDELVION powder vial on a firm, flat surface. Invert the solvent vial with the Mix2Vial attached and push the transparent adapter end downward until it engages into the stopper of the IDELVION vial. The solvent will automatically transfer into the IDELVION vial.
5	With one hand, hold the side of the IDELVION vial connected to the Mix2Vial and, with the other hand, hold the side of the solvent vial. Carefully unscrew the transfer system counterclockwise to separate it into two parts. Discard the solvent vial with the attached blue Mix2Vial adapter.
6	Gently rotate the IDELVION vial with the attached transparent adapter until the substance is completely dissolved. Do not shake.
7	Fill a sterile empty syringe with air. While keeping the IDELVION vial in an upright position, attach the syringe to the Luer-Lock adapter of the attached Mix2Vial by screwing it clockwise. Inject air into the IDELVION vial.

Transfer and administration

8	While keeping pressure on the syringe plunger, turn the system upside down and slowly pull back the plunger to draw the solution into the syringe.
9	Once the solution has been transferred to the syringe, firmly hold the syringe barrel (keeping the plunger facing downward) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing it counterclockwise.

Use the venipuncture kit supplied with the product and insert the needle into a vein. Allow the blood to flow until the end of the tube. Attach the syringe to the threaded locking end of the venipuncture kit. Slowly inject the reconstituted solution (at a rate comfortable for you, up to a maximum of 5 mL/min) into the vein, according to the instructions given by your doctor. Try to prevent blood from entering the syringe containing the product.

Check whether you experience any adverse effects immediately after the injection. If you experience any adverse reaction that may be related to the administration of IDELVION, the injection must be stopped (see also sections 2 and 4).

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Contact your doctor:

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

• if you notice that the medicine stops working properly.

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

• Hypersensitivity-type allergic reactions (common) may occur, including the following symptoms: erythema, skin itching (generalized urticaria), chest tightness, difficulty breathing, low blood pressure (hypotension), and anaphylaxis (a serious reaction causing severe breathing difficulty and dizziness). If this occurs, you must immediately stop administering the medicine and contact your doctor.

• Inhibitors: the medicine stops working properly (ongoing bleeding). You may develop a factor IX inhibitor (neutralizing antibody) (frequency unknown), meaning that factor IX will no longer work effectively. If this occurs, you must immediately stop administering the medicine and contact your doctor.

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

• Headache
• Reactions at the injection site
• Dizziness
• Skin rash

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

• Eczema

Adverse effects in children and adolescents

Adverse effects in children are expected to be the same as those in adults.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 its carton to protect from light.

• After reconstitution, the product should preferably be used immediately.

If the reconstituted product is not administered immediately, the storage times and conditions prior to use are the responsibility of the user.

6. Contents of the pack and other information

Composition of IDELVION

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 and hydrochloric acid (for pH adjustment).

See the last paragraph of section 2.

Solvent: water for injections

Appearance of IDELVION and contents of the pack

IDELVION is presented as a yellow to white powder and is supplied with a solvent in the form of water for injections.

The reconstituted solution should be transparent or slightly opalescent, yellow to colourless; that is, it may shimmer when exposed to light but must not contain any visible particles.

Presentations

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

1 vial of powder

1 vial containing 2.5 ml of water for injections

1 transfer device with 20/20 filter

Administration set (inner box):

1 disposable 5 ml syringe

1 venipuncture set

2 alcohol-impregnated wipes

1 non-sterile dressing

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

1 vial of powder

1 vial containing 5 ml of water for injections

1 transfer device with 20/20 filter

Administration set (inner box):

1 disposable 10 ml syringe

1 venipuncture set

2 alcohol-impregnated wipes

1 non-sterile dressing

Only certain pack sizes may be marketed.

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:

Belgium/Belgium/Belgium CSL Behring NV Tel/Tel: +32 15 28 89 20	Lithuania CentralPharma Communications UAB Tel: +370 5 243 0444
	Luxembourg/Luxembourg CSL Behring NV Tel/Tel: +32 15 28 89 20
Czech Republic CSL Behring s.r.o. Tel: + 420 702 137 233	Hungary CSL Behring Kft. Tel.: +36 1 213 4290
Denmark CSL Behring AB Tlf: +46 8 544 966 70	Malta AM Mangion Ltd. Tel: +356 2397 6333
Germany CSL Behring GmbH Tel: +49 6190 75 84810	Netherlands CSL Behring BV Tel: + 31 85 111 96 00
Estonia CentralPharma Communications OÜ Tel: +3726015540	Norway CSL Behring AB Tlf: +46 8 544 966 70
Greece CSL Behring ΕΠΕ Tel: +30 210 7255 660	Austria CSL Behring GmbH Tel: +43 1 80101 1040
Spain CSL Behring S.A. Tel: +34 933 67 1870	Poland CSL Behring Sp.z o.o. Tel: +48 22 213 22 65
France CSL Behring S.A. Tél: + 33 –(0)-1 53 58 54 00	Portugal CSL Behring Lda Tel: +351 21 782 62 30
Croatia Marti Farm d.o.o. Tel: +385 1 5588297	Romania Prisum Healthcare S.R.L. Tel: +40 21 322 0171
Ireland CSL Behring GmbH Tel: +49 6190 75 84700 Iceland CSL Behring AB Sími: +46 8 544 966 70	Slovenia Emmes Biopharma Global s.r.o. podružnica v Sloveniji Tel:+ 386 41 42 0002 Slovakia CSL Behring Slovakia s.r.o. Tel: +421 911 653 862
Italy CSL Behring S.p.A. Tel: +39 02 34964 200	Finland/Suomi CSL Behring AB Puh/Tel: +46 8 544 966 70
Cyprus CSL Behring ΕΠΕ Τηλ: +30 210 7255 660	Sweden CSL Behring AB Tel: +46 8 544 966 70
Latvia CentralPharma Communications SIA Tel: +371 6 7450497

Date of the most recent review of this summary:

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu, and on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

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This information is intended for healthcare professionals only:

Dosage

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

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 (relative to an international standard for plasma factor IX).

One International Unit (IU) of factor IX activity corresponds 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 IU of factor IX per kg of body weight increases plasma factor IX activity by a mean of 1.3 IU/dl (1.3% of normal activity) in patients ≥ 12 years of age and by 1.0 IU/dl (1.0% of normal activity) in patients < 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 level or IU/dl) × {observed reciprocal recovery (IU/kg per IU/dl)}

Predicted increase in factor IX (IU/dl or % of normal level) = dose (IU) × recovery (IU/dl per IU/kg) / body weight (kg)

The dose and frequency of administration should always be adjusted according to the observed clinical efficacy in each individual case.

Patients < 12 years of age

In cases with 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

Examples:

1. A maximum 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 produce a maximum increase in factor IX after injection of 1,000 IU / 25 kg × 1.0 (IU/dl per IU/kg) = 40 IU/dl (40% of normal level).

Patients ≥ 12 years of age

In cases with 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

Examples:

1. A maximum 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.

2. A dose of 2,000 IU of IDELVION administered to an 80 kg patient is expected to produce a maximum increase in factor IX after injection of 2,000 IU × 1.3 (IU/dl per IU/kg) / 80 kg = 32.5 IU/dl (32.5% of normal level).

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

Degree of bleeding/ type of surgical procedure	Required factor IX level (% or IU/dL)	Dosing frequency (hours)/duration of treatment (days)
Minor or moderate bleeding Hemarthrosis, muscle bleeding (except iliopsoas), or oral cavity bleeding	30–60	A single dose should be sufficient in most cases. A maintenance dose should be administered after 24–72 hours if further evidence of bleeding occurs.
Major bleeding Potentially life-threatening bleeding, deep muscle bleeding, including iliopsoas	60–100	Repeat every 24–72 hours during the first week, then administer a maintenance dose weekly until bleeding stops and wound is healed.
Minor surgery For example, (including uncomplicated dental extractions)	50–80 (pre- and postoperative)	A single dose should be sufficient in most minor procedures. If necessary, a maintenance dose may be administered after 24–72 hours until bleeding stops and wound is healed.
Major surgery	60–100 (pre- and postoperative)	Repeat every 24–72 hours during the first week, then administer a maintenance dose 1–2 times per week until bleeding stops and wound is healed.

Prophylactic treatment

For long-term prophylaxis to prevent bleeding in patients with severe hemophilia B, the usual dose is 35 to 50 IU/kg once weekly. Patients well-controlled on a once-weekly regimen may be treated with up to 75 IU/kg every 10 or 14 days. In patients > 18 years of age, a longer extension of the treatment interval may be considered.

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

After a bleeding episode during prophylaxis, patients should maintain their prophylactic regimen as much as possible, with administration of 2 doses of IDELVION at least 24 hours apart, but longer intervals when considered appropriate for the patient.

Pediatric population

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

Warnings and special precautions for use

Inhibitors

Following repeated treatment with human coagulation factor IX products, patients should be monitored for the development of neutralizing antibodies (inhibitors), which should be quantified in Bethesda Units (BU) using appropriate biological assays.

Literature reports have shown a correlation between the development of factor IX inhibitors and allergic reactions. Therefore, patients experiencing allergic reactions should be evaluated for the presence of an inhibitor. It should be considered that patients with factor IX inhibitors may have an increased risk of anaphylaxis upon subsequent exposure to factor IX.

Monitoring of treatment

During treatment, it is recommended to adequately monitor factor IX levels to determine the appropriate dose and frequency of infusions. Patients' responses to factor IX may vary, reflecting differences in half-life and recovery. Dose based on body weight may need adjustment in patients who are underweight or overweight. In the special case of major surgical procedures, replacement treatment must be closely monitored using coagulation assays (plasma factor IX activity).

When using a one-stage coagulation assay based on activated partial thromboplastin time (aPTT) in vitro to determine 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. Measurement performed with a one-stage coagulation assay using a kaolin-based aPTT reagent or an aPTT reagent with Actin FS is likely to result in underestimation of the activity level. This is particularly important when changing laboratories or reagents used in the assay.