IDELVION 250 IU Powder and solvent for injectable solution

Зміст інструкції

1. IDELVION 250 IU powder and solvent for injectable solution, 500 IU powder and solvent for injectable solution, 1 000 IU powder and solvent for injectable solution, 2 000 IU powder and solvent for injectable solution, 3 500 IU powder and solvent for injectable solution
   1. What is IDELVION and what is it used for
   2. What you need to know before you take IDELVION
   3. How to take IDELVION
   4. Possible side effects
   5. How to store IDELVION
   6. Content of the pack and other information

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

albutrepenonacog alfa (recombinant coagulation factor IX)

contains important information for you.

• If you have any doubts, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If any side effects occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.
• 1. What IDELVION is and what it is used for
• 2. What you need to know before you are given 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 is IDELVION and what is it used for

What is IDELVION?
IDELVION is a medicine for haemophilia that replaces the natural coagulation factor IX.
The active ingredient of IDELVION is albutrepenonacog alfa recombinant fusion protein
consisting of coagulation factor IX with albumin (rIX-FP)).
Factor IX is involved in blood coagulation. Patients affected by haemophilia B have a
deficiency of this factor which causes the blood not to clot at a normal rate and this causes a
tendency to bleed. IDELVION works by replacing factor IX in patients with haemophilia B to
allow the blood to clot.

What is IDELVION used for?
IDELVION is used to prevent or stop bleeding caused by a deficiency of
factor IX in patients of all age groups with haemophilia B (also known as congenital factor IX deficiency or Christmas disease).

2. What you need to know before you take IDELVION

Do not take IDELVION

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

Warnings and precautions
It is strongly recommended that with each use of IDELVION you record the name and lot number
of the product to keep track of the products and lot numbers used.
Consult your doctor, pharmacist or nurse before taking IDELVION.

• Hypersensitivity reactions of an allergic type are possible. The medicine contains traces of hamster proteins (See also “Do not take IDELVION”). If symptoms of allergic reactions appear, immediately stop using the medicine and consult yourdoctor or the care center where you are followed. Your doctor will inform you about the firstsigns of hypersensitivity reactions. These include: hives, widespread rash, chest tightness, wheezing, low blood pressure (hypotension) and anaphylaxis (a severe allergic reaction that causes severe difficulty breathing or dizziness).
• Due to the risk of allergic reactions with Factor IX, the first administration of IDELVION must be carried out under strict medical observation in case it is necessary to intervene with appropriate care for allergic reactions.
• The formation of inhibitors(neutralizing antibodies) is a known complication that has been observed during treatment with IDELVION. Inhibitors prevent the treatment itself from working properly. If IDELVION is not effective against bleeding episodes, inform your doctor immediately. You should be regularly monitored for the possible development of inhibitors.
• If you suffer from liver or heart disease or if you have recently undergone major surgery, please inform your doctor, as there is an increased risk of complications due to blood clot formation (coagulation).
• If a central venous access device (CVAD for injection of IDELVION) is required, your doctor should consider the risk of complications including local infections, bacteria in the blood (bacteremia) and the formation of a blood clot in the blood vessel (thrombosis) where the catheter is inserted.

Other medicines and IDELVION

• Tell 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 to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine. During pregnancy and breastfeeding, IDELVION should only be administered if absolutely necessary. Driving and using machinesIDELVION does not affect the ability to drive vehicles and use machines.

IDELVION contains sodium
This medicine contains up to 8.6 mg of sodium (the main component of table salt) in each
vial. This is equivalent to 0.4% of the recommended maximum daily intake of sodium 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 your doctor has told you. Check with your
doctor if you are not sure.
The doctor will determine the necessary dose of IDELVION. The amount of IDELVION needed to
be taken and the duration of treatment depend on the following:

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

IDELVION is administered by your doctor or nurse by injection into a vein (intravenous, IV)
after reconstitution of the powder with the provided solvent. You or someone else may
administer IDELVION by intravenous injection, but only after receiving adequate
training.
If you have taken too much IDELVION
Immediately inform the doctor if an IDELVION dose higher than that
recommended by the doctor has been injected.
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 drawn from the vial while keeping the medicine sterile (germ-free). The doctor will show you how to prepare the solution and how to correctly draw 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, from yellow to colorless, may exhibit some shimmer when exposed to light but should not contain any visible particles. After filtration/withdrawal (see below), the reconstituted solution must be visually inspected before administration. Do not use the solution if it appears cloudy or if it contains deposits or particles.
• Unused medicine and waste materials derived from such medicine must be disposed of in accordance with current local regulations and according to the doctor's instructions.

Reconstitution
Without opening the vials, bring the IDELVION powder and the liquid to room temperature or to
body temperature. This can be done by leaving the vials at room temperature for about
one hour or by holding them in your hand for a few minutes.
DO NOT expose the vials to direct heat. The vials must not be brought to temperatures
higher than body temperature (37 °C).
Carefully remove the protective cap from the vials and clean the exposed rubber stopper with a
swab soaked in alcohol. Allow the vials to dry before opening the Mix2Vial package
(containing the transfer filter device) and then follow the instructions below.

e g 1

1. Open the Mix2Vial by detaching the lid. 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 the entire package and push the blue terminal part directly into the cap of the vial containing the solvent.
3	a 3. Carefully remove the package from the m Mix2Vial by holding it by the edge and pulling vertically upwards. Make sure to remove only the blister pack and not the Mix2Vial. r
4	a F 4. Place the IDELVION vial on a flat and stable surface. Invert the solvent vial with the Mix2Vial attached and push the tip of the transparent adapter l down through the cap of the IDELVION vial. The solvent will flow automatically into the vial containing IDELVION.
5	d 5. With one hand grasp the side with IDELVION of the Mix2Vial and with the other hand grasp the side with the solvent, carefully unscrewing in a counterclockwise direction to separate the device into two parts. Eliminate the solvent vial with the blue Mix2Vial adapter attached.
6	a i 6. Gently rotate the IDELVION vial with the attached transparent adapter until the substance is completely dissolved. Do not shake.
I a i z n 7	t 7. Draw air into a sterile, empty syringe. Holding the IDELVION vial in a vertical position, connect the syringe to the Luer Lock fitting of the Mix2Vial by screwing clockwise. Inject air into the IDELVION vial.

Withdrawal and administration

8	8. While holding down the syringe plunger, invert the device and draw the solution into the syringe by slowly pulling back the plunger. a
9	m 9. Now that the solution has been transferred into the syringe, firmly grasp the body of the syringe r (with the plunger facing downwards) and a disconnect the transparent adapter of the Mix2Vial from the syringe by unscrewing in a counterclockwise direction. F

Use the injection device provided with the product, inserting the needle into a vein.
Allow blood to reflux at the end of the tube. Apply the syringe to the threaded closing end
of the intravenous injection device. Slowly inject the reconstituted solution (as is
most comfortable, up to a maximum of 5 mL/min) into the veinfollowing the instructions provided by the doctor.
Avoid allowing blood to enter the syringe containing the medicine.
Check for any adverse effects that may occur immediately. If you notice the onset of adverse
effects that may be related to the administration of IDELVION, you must stop the
administrations (see also sections 2 and 4).
If you have any further questions about the use of this medicine, consult your doctor or pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
manifest.

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:

• Hypersensitivity reactions of an allergic type are possible (common) and may include the following symptoms: urticaria, skin rash (generalised urticaria), chest tightness, wheezing, low blood pressure (hypotension) and anaphylaxis (serious allergic reaction that causes severe difficulty breathing or dizziness). In these cases, stop taking the medicine immediately and contact your doctor.
• Inhibitors: the medicine no longer works properly (continuous bleeding). It is possible that an inhibitor (neutralising antibody) against factor IX has developed (frequency not known), in which case factor IX no longer works properly. In these cases, stop taking the medicine immediately and contact your doctor.

The following side effects have been observed commonlywith IDELVION (may affect 1
person in 10):

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

The following side effects have occurred not commonly(may affect 1 person in 100):

• 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 experience any side effects, even those not listed in this leaflet,
tell your doctor or pharmacist or nurse. You can also report side effects directly through the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help to 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, indicated on the label and the packaging.
• Do not store at a temperature above 25 °C.
• Do not freeze.
• Keep the vial in the outer packaging in order to protect it from light.
• The reconstituted medicine should preferably be used immediately.
• If the reconstituted medicine is not administered immediately, the storage times and conditions before use are the responsibility of the user.

6. Content of the pack and other information

What IDELVION contains
The active ingredient is as follows:
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 ingredients are as follows:
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 presented as a powder ranging in colour from pale yellow to white and is supplied with
water for injections as a solvent.
The reconstituted solution appears from transparent to slightly opalescent, from yellow to colourless, or
may be bright when viewed against the light but should not contain visible particles.
Presentations
A pack of 250, 500 or 1 000 IU containing:
1 vial with powder
1 vial with 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 venous injection set
2 alcohol-soaked swabs
1 non-sterile plaster
A pack of 2 000 or 3 500 IU containing:
1 vial with powder
1 vial with 5 mL of water for injections
1 transfer device with 20/20 filter
An inner carton containing:
1 single-use 10 mL syringe
1 venous injection set
2 alcohol-soaked swabs
1 non-sterile 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 on this medicine, please contact the local representative of the Marketing
Authorisation Holder:

België/Belgique/Belgien
CSL Behring NV
Tél/Tel: +32 15 28 89 20

Lietuva
CentralPharma Communications UAB
Tel: +370 5 243 0444

България
МагнаФарм България ЕАД
Тел: +359 2 810 3949

Luxembourg/Luxemburg
CSL Behring NV
Tél/Tel: +32 15 28 89 20

Česká republika
CSL Behring s.r.o.
Tel: + 420 702 137 233

Magyarország
CSL Behring Kft.
Tel.: +36 1 213 4290

Danmark
CSL Behring AB
Tel: +46 8 544 966 70

Malta
AM Mangion Ltd.
Tel: +356 2397 6333

Nederland
CSL Behring BV
Tel: + 31 85 111 96 00

Deutschland
CSL Behring GmbH
Tel: +49 69 30584437

Norge
CSL Behring AB
Tlf: +46 8 544 966 70

Eesti
CentralPharma Communications OÜ
Tel: +3726015540

Österreich
CSL Behring GmbH
Tel: +43 1 80101 2463

Ελλάδα
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

España
CSL Behring S.A.
Tel: +34 933 67 1870

Polska
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

Hrvatska
Marti Farm d.o.o.
Tel: +385 1 5588297

România
Prisum Healthcare srl
Tel: +40 21 322 0171

Ireland
CSL Behring GmbH
Tel: +49 69 30517254

Slovenija
Emmes Biopharma Global s.r.o.-podružnica v
Sloveniji
Tel:+ 386 41 42 0002

Ísland
CSL Behring AB
Sími: +46 8 544 966 70

Slovenská republika
CSL Behring s.r.o.
Tel: + 421 911 653 862

Italia
CSL Behring S.p.A.
Tel: +39 02 34964 200

Suomi/Finland
CSL Behring AB
Puh/Tel: +46 8 544 966 70

Κύπρος
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

Sverige
CSL Behring AB
Tel: +46 8 544 966 70

Latvija
CentralPharma Communications SIA
Tel: +371 6 7450497

United Kingdom (Northern Ireland)
CSL Behring GmbH
Tel: +49 69 305 17254
More detailed information on this medicine is available on the website of the European Medicines
Agency: http://www.ema.europa.eu.
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The following information is intended exclusively for healthcare professionals:
Dosage and administration
The dose and duration of replacement therapy depend on the severity of the factor IX deficiency, the
site and extent of the bleeding and the patient’s clinical condition.
The number of units of factor IX administered is expressed in International Units (IU) in
reference to the current WHO standard for factor IX products. Plasma activity of factor
IX is expressed as a percentage (relative to normal human plasma) or in International Units
(according to an international standard for factor IX in plasma).
One International Unit (IU) of factor IX is equivalent to the amount of factor IX contained in one
mL of normal human plasma.

On-demand treatment (as needed)
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 the activity of factor IX in plasma by approximately 1.3 IU/dL (1.3% of normal
activity) in patients aged 12 years or older and 1.0 IU/dL (1.0% of normal activity) in
patients under 12 years of age. The required dose is established using the following formula:
Required dose (IU) = body weight (kg) x desired increase in factor IX (% of normal or
IU/dL) x {reciprocal of observed recovery (IU/kg per IU/dL)}
Expected increase in factor IX (IU/dL or % of normal) = Dose (IU) x Recovery (IU/dL per IU/kg)/body
weight (kg)
The amount and frequency of administration must 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) x desired increase in factor IX (IU/dL) x 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 x 50 IU/dL x 1 dL/kg = 1 000 IU.
• 2. A dose of 1 000 IU of IDELVION, administered to a 25 kg patient, should result in a post-injection factor IX level of 1 000 IU/25 kg x 1.0 (IU/dL per IU/kg) = 40 IU/dL (40% of normal).

Patients aged 12 years or 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) x desired increase in factor IX (IU/dL) x 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 x 50 IU/dL x 0.77 dL/kg = 3 080 IU.
• 4. A dose of 2 000 IU of IDELVION, administered to an 80 kg patient, should result in a peak post-injection factor IX level of 2 000 IU x 1.3 (IU/dL per IU/kg)/80 kg = 32.5 IU/dL (32.5% of normal).

Should any of the following bleeding events occur, the factor IX activity should not
fall below a given level of plasma activity (as a percentage of the
normal or IU/dL) during the corresponding period. The following table can be used as
a guide for dosage in case of bleeding and surgery:

Prophylaxis
In patients with severe haemophilia B, the usual dose for long-term prophylaxis of
bleeding is 35 – 50 IU/kg, once a week.
Some patients who show optimal disease control with a once-weekly administration regimen may switch to a dose of up to 75 IU/kg, at intervals of
administration every 10 or 14 days. For patients over 18 years of age, further extension of the dosing interval may be considered (see section 5.1).
In some cases, especially in younger patients, shorter intervals or
higher doses may be necessary.
Following an episode of bleeding during prophylaxis, patients should strictly adhere to
their prophylaxis regimen, with 2 doses of IDELVION administered at least 24
hours apart or with a longer interval, if deemed appropriate for the patient.
Paediatric population
For long-term prophylaxis, the recommended dose regimen is 35-50 IU/kg, once a
week. For adolescents aged 12 years or older, the dosage recommendations are the
same as for adults (see above).

Special warnings and precautions for use
Inhibitors
After repeated treatments with human coagulation factor IX-containing medicinal products, patients
should be monitored for the possible development of neutralising antibodies (inhibitors), which must
be quantified in Bethesda Units (BU), using appropriate biological controls.
Cases have been described in the literature in which a correlation has been demonstrated between the occurrence of factor IX inhibitors and allergic reactions. For this reason, patients who experience allergic reactions
should be tested for the presence of inhibitors. It should be emphasised that patients with
factor IX inhibitors may be at higher risk of anaphylaxis following subsequent administrations
of factor IX.
Monitoring of treatment
During treatment, appropriate determination of factor IX levels is advisable to establish the dose to be administered and the frequency of infusions. There may be differences between
individual patients in the response to factor IX, indicating different half-lives and recoveries. Dose calculation based on body weight may require correction in underweight or overweight patients.
Especially in the case of major surgery, accurate monitoring of
replacement therapy through coagulation analysis (plasma factor IX activity) is essential.
When using a “one-stage” in vitrocoagulation test, based on activated partial thromboplastin time (aPTT) for the determination of 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 test. Measurement with a “one-stage” coagulation test using a kaolin-based aPTT reagent or an aPTT reagent based on Actin FS will likely underestimate the activity level. This
is particularly important when changing the laboratory and/or the reagents used in the test.
* * *