AFSTYLA 1000 IU Powder and solvent for injectable solution

Зміст інструкції

1. AFSTYLA 250 IU powder and solvent for injectable solution, 500 IU powder and solvent for injectable solution, 1000 IU powder and solvent for injectable solution, 1500 IU powder and solvent for injectable solution, 2000 IU powder and solvent for injectable solution, 2500 IU powder and solvent for injectable solution, 3000 IU powder and solvent for injectable solution
   1. What is AFSTYLA and what is it used for
   2. What you need to know before you or your child use AFSTYLA
   3. How to use AFSTYLA
   4. Possible side effects
   5. How to store AFSTYLA
   6. Contents of the pack and other information

• B. PACKAGE LEAFLET

AFSTYLA 250 IU powder and solvent for injectable solution, 500 IU powder and solvent for injectable solution, 1000 IU powder and solvent for injectable solution, 1500 IU powder and solvent for injectable solution, 2000 IU powder and solvent for injectable solution, 2500 IU powder and solvent for injectable solution, 3000 IU powder and solvent for injectable solution

lonoctocog alfa (recombinant coagulation factor VIII single chain)

medicine because it contains important information for you.

• If you have any doubts, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed only for you or your child. Do not give it to other people, even if their symptoms are the same as yours, as it could be dangerous.
• If any side effect occurs, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is AFSTYLA and what is it used for

AFSTYLA is a medicine based on human coagulation factor VIII produced using recombinant DNA technology. The active substance contained in AFSTYLA is lonoctocog alfa.
AFSTYLA is used to treat and prevent any bleeding episodes in patients affected by haemophilia A (congenital factor VIII deficiency). Factor VIII is a protein necessary during the blood coagulation process. Patients with haemophilia A lack this protein, consequently the blood does not clot quickly enough and they have an increased tendency to bleed. AFSTYLA works by replacing the missing factor VIII in the blood of patients with haemophilia A, allowing it to coagulate normally.
AFSTYLA can be used in patients of any age.

2. What you need to know before you or your child use AFSTYLA

Do not use AFSTYLA

• if the patient treated with AFSTYLA has had an allergic reaction to AFSTYLA or to any of its ingredients (listed in section 6).
• if the patient treated with AFSTYLA is allergic to hamster proteins.

Warnings and precautions
Traceability
It is important to keep track of the batch number of your AFSTYLA.
Therefore, each time you receive a new package of AFSTYLA, note the date and batch number
(which is located on the packaging after "Lot") and keep this information in a safe place.
Consult your doctor, pharmacist or nurse before using AFSTYLA.

• Allergic-type (hypersensitivity) reactions are possible. The medicine contains traces of hamster proteins (see also “Do not use AFSTYLA”). If you experience symptoms of allergic reactions, stop using the medicine immediately and contact your doctor.The doctor will inform you about theearly symptoms of allergic reactions. These include urticaria, widespread rash, a feeling of tightness in the chest, wheezing, hypotension and anaphylaxis (a severe allergic reaction that causes severe difficulty breathing and dizziness).
• The formation of inhibitors(antibodies) is a known complication that can occur during treatment with all factor VIII-based medicines. Inhibitors, especially at high levels, prevent the treatment from working properly and you or your child will be closely monitored for the development of inhibitors. If AFSTYLA does not control bleeding in you or your child, inform your doctor immediately.
• If you or your child know you have or are at risk of heart disease, inform your doctor or pharmacist.
• If a central venous access device (CVAD) is used to administer AFSTYLA, the doctor must consider and discuss with you the risk of complications, including local infections, the presence of bacteria in the blood (bacteremia) and the formation of a blood clot (thrombosis) in the blood vessel where the catheter was inserted.

Other medicines and AFSTYLA
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicine.

Pregnancy and breastfeeding

• If you are pregnant or breastfeeding, if you suspect or are planning a pregnancy, ask your doctor or pharmacist for advice before taking this medicine.
• During pregnancy and breastfeeding, AFSTYLA should only be administered if absolutely necessary.

Driving and using machines
AFSTYLA does not affect the ability to drive and use machines.

AFSTYLA contains sodium
AFSTYLA may contain up to 35.0 mg of sodium (the main component of table salt) per
vial. This is equivalent to 1.8% of the maximum recommended daily intake of sodium for
an adult.

3. How to use AFSTYLA

Treatment must occur under the supervision of a physician experienced in the treatment of coagulation disorders.
AFSTYLA must always be administered as directed by your doctor. Consult your doctor if you have
any doubts.

Dosage
The amount of AFSTYLA to be administered to you or your child and the duration of treatment depend on:

• the severity of your condition
• the site and intensity of the bleeding
• your clinical condition and your response to treatment
• your body weight.

Always follow the instructions provided by your doctor.

Reconstitution and administration
General instructions

• The powder must be mixed with the solvent (liquid) and drawn from the vial under aseptic conditions.
• AFSTYLA 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; it may exhibit some sparkle when exposed to light but should not, however, contain any visible particles. Once filtered or drawn up (see below), the solution must be checked again before use. Do not use solutions that are visibly cloudy or contain particles or deposits.
• Any unused product or waste materials must be disposed of in accordance with current local regulations and according to your doctor's instructions.

Reconstitution and administration
Without opening the vials, ensure that the powder and liquid of AFSTYLA are at room or body
temperature, for example, by leaving the vials at room temperature for about an hour or
holding them in your hand for a few minutes.
Do not expose the vials to direct heat. The vials must not be brought to a temperature higher
than body temperature (37°C).
Carefully remove the protective caps from the vials and clean the exposed rubber stopper
using an alcohol-soaked swab. Allow the vials to dry before opening the
Mix2Vial kit packaging (containing the transfer device with filter), then, follow the
instructions below:

1	n 1. Open the Mix2Vial kit by removing the thin protective film. Do not remove the Mix2Vial kit from the packaging!
2	l 2. Place the solvent vial on a flat and clean surface, holding it firmly. Then, take the Mix2Vial kit together with its packaging and, by pressing the blue-colored adapter tip downwards, puncture the stopper of the solvent vial.
i z n 3	a 3. Carefully remove the Mix2Vial kit packaging by grasping it by the edge and pulling it upwards, making sure to remove only the packaging and not the entire Mix2Vial kit.
e g A 4	4. Place the powder vial on a flat and stable surface. Invert the solvent vial connected to the Mix2Vial kit and, by pushing the transparent adapter tip downwards, puncture the stopper of the powder vial. The solvent will automatically be transferred into the powder vial.

5	5. Holding one side of the Mix2Vial kit with one hand, grasp the solvent side with the other and separate the two parts that make up the kit by carefully unscrewing them counterclockwise. c Dispose of the solvent vial with the blue-colored adapter of the Mix2Vial kit attached to it.
6	m 6. Gently rotate the product vial with the transparent adapter attached until the contents are completely dissolved. Do not shake.
7	a 7. Draw air into a sterile empty syringe. Holding the product vial in a vertical position, connect the syringe to the “Luer Lock” connector of the Mix2Vial kit by screwing it on clockwise. Inject air into the product vial.

Withdrawal and administration

8	a n 8. Holding the syringe plunger pressed down, invert the system and draw the solution into the syringe by slowly pulling back on the plunger.
i z 9	t 9. Once the solution has been drawn into the syringe, holding the body of the syringe firmly (with the plunger facing downwards), disconnect the transparent adapter of the Mix2Vial kit from it by unscrewing it counterclockwise.

Use the injection set provided with the product, insert the needle into a vein. Allow blood to flow back into the tubing at its end. Insert the syringe nozzle into the threaded connector of the cannula needle. Slowly inject the reconstituted solution (at the speed that is most comfortable for you, up to a maximum of 10 mL/min) intravenously, following the doctor's instructions. Make sure not to allow any blood to enter the syringe containing the product.
Check for any immediate adverse reactions. If you notice the onset of adverse reactions potentially attributable to the administration of AFSTYLA, stop the infusion (see section 2).

Use in children and adolescents
AFSTYLA can be used in children and adolescents of all ages. In children under 12 years of age, it may be necessary to administer higher doses or more frequent infusions. Children over 12 years of age can use the same doses as adults.

If you use more AFSTYLA than you should
If you have injected more AFSTYLA than you should, tell your doctor.

If you forget to use AFSTYLA
Do not inject a double dose to make up for the one you forgot to take. Proceed
directly with the next dose and continue therapy as advised by your doctor.

If you stop using AFSTYLA
If you stop using AFSTYLA, you may no longer be protected against bleeding or
an ongoing hemorrhage may not stop. Do not stop using AFSTYLA without first
consulting your doctor.
If you have any doubts about using this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

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

Stop using the medicine immediately and contact your doctor if:

• you experience symptoms of allergic reactionsAllergic reactions can manifest with the following symptoms: hives, widespread rash (itchy rash), feeling of tightness in the chest, wheezing, low blood pressure, and anaphylaxis (a severe allergic reaction that causes severe difficulty breathing or dizziness). In such a case, stop using the medicine immediately and contact your doctor.
• you notice that the medicine has stopped working as it should(bleeding does not stop) In children not previously treated with factor VIII-based medicines, the formation of inhibitor antibodies (see section 2) may be very common (more than 1 in 10 patients); however, in patients who have received previous treatment with factor VIII (more than 150 days of treatment) this is uncommon (less than 1 in 100 patients). If you or your child have developed an inhibitor with this medicine, you or your child may experience persistent bleeding. If this happens, you should contact your doctor immediately.

Common side effects (may affect up to 1 in 10 people)

• tingling or numbness (paresthesia)
• rash
• fever

Uncommon side effects (may affect up to 1 in 100 people)

• itching
• skin redness
• pain at the injection site
• shivers
• feeling of warmth

Side effects in children and adolescents
No age-specific differences have been observed between children, adolescents, and adults regarding
the occurrence of side effects.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly
through the national reporting system listed in Annex V.
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store AFSTYLA

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the label and the packaging.
• Store this medicine in a refrigerator (between 2°C and 8°C).
• Before reconstitution, store AFSTYLA at room temperature (not exceeding 25°C) for a maximum period of 3 months before the expiry date reported on the packaging and on the vial label. Remember to note the date of the start of storage of AFSTYLA at room temperature on the product packaging.
• Once the medicine has been removed from the refrigerator, do not put it back in the refrigerator.
• Do not freeze this medicine.
• Store the vials inside the outer packaging to protect the medicine from light.
• Preferably, use the reconstituted medicine immediately.
• In the event that it is not used immediately, taking the reconstituted product within times and under storage conditions different from those prescribed will be under the exclusive responsibility of the user.

6. Contents of the pack and other information

What AFSTYLA 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 lonoctocog alfa.
500 IU per vial; after reconstitution with 2.5 mL of water for injections, the
solution contains 200 IU/mL of lonoctocog alfa.
1000 IU per vial; after reconstitution with 2.5 mL of water for injections, the
solution contains 400 IU/mL of lonoctocog alfa.
1500 IU per vial; after reconstitution with 5 mL of water for injections, the
solution contains 300 IU/mL of lonoctocog alfa.
2000 IU per vial; after reconstitution with 5 mL of water for injections, the
solution contains 400 IU/mL of lonoctocog alfa.
2500 IU per vial; after reconstitution with 5 mL of water for injections, the
solution contains 500 IU/mL of lonoctocog alfa.
3000 IU per vial; after reconstitution with 5 mL of water for injections, the
solution contains 600 IU/mL of lonoctocog alfa.
The other ingredients are:
L-histidine, polysorbate 80, calcium chloride dihydrate, sodium chloride (see the last part of paragraph
2), sucrose.
Solvent: water for injections.

What AFSTYLA looks like and contents of the pack
AFSTYLA is presented as a powder or friable mass ranging in colour from white to
yellowish and a clear, colourless solvent for injection.
The reconstituted solution should be clear or slightly opalescent, ranging in colour from yellow
to colourless; it may exhibit some sparkle when exposed to light but should not contain any visible
particles.
Presentations
A pack of 250, 500 or 1000 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 1500, 2000, 2500 or 3000 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.
Primary packaging

Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Straße 76
35041 Marburg
Germany
For information on the medicinal product, 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
Tlf: +46 8 544 966 70

Malta
AM Mangion Ltd.
Tel: +356 2397 6333

Deutschland
CSL Behring GmbH
Tel: +49 69 30584437

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

Eesti
CentralPharma Communications OÜ
Tel: +3726015540

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

Ελλάδα
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

Österreich
CSL Behring GmbH
Tel: +43 1 80101 2463

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 S.R.L
Tel: +40 21 322 0171

Ireland
CSL Behring UK Ltd.
Tel: +44 1444 447405

Slovenija
NEOX 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
For detailed information on this medicinal product, please visit the website of the
European Medicines Agency at http://www.ema.europa.eu
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The following information is intended exclusively for healthcare professionals:
Treatment must take place under the supervision of a physician experienced in the treatment of haemophilia.
Treatment monitoring
During treatment, adequate determination of factor VIII levels is recommended in order to
establish the dose to be administered and the frequency with which infusions should be repeated. The
response to factor VIII may vary from patient to patient and different half-lives and different in vivo
recovery levels may be observed in individual patients. Dosage based on body weight may require
dose adjustments in underweight or overweight patients. In particular, in the case of major surgery,
precise and careful monitoring of substitute therapy by means of coagulation analysis (plasma factor VIII
activity) is essential. If the activity of factor VIII in patients’ blood samples is determined by one-stage
in vitrotests for the determination of activated partial thromboplastin time (aPTT), the results may be
significantly altered by both the type of aPTT reagent and the reference standard used for performing
the test. Significant discrepancies may also emerge between the results obtained by one-stage aPTT tests
and those obtained using the chromogenic method specified by the European Pharmacopoeia. This is
particularly important if the test is performed in a different laboratory and/or with different reagents.
Plasma factor VIII activity in patients receiving AFSTYLA should be monitored by chromogenic method
or by one-stage coagulation tests to manage the administered dose and the frequency of repeat injections. The
chromogenic method is considered the preferred method, as it is best able to accurately express the clinical
haemostatic potential of AFSTYLA. Compared to those obtained by chromogenic method, the results of the
one-stage coagulation test underestimate the levels of factor VIII activity by approximately 45%. If the one-stage
coagulation test is used, the result must be multiplied by a conversion factor of 2 in order to determine the
patient’s factor VIII activity level.
Dosage
The dosage and duration of substitute therapy depend on the severity of the factor VIII deficiency,
the site and extent of the bleeding and the patient’s clinical condition.
The number of units of factor VIII administered is expressed in International Units (IU), a unit of
measurement established on the basis of current WHO standards for factor VIII-based concentrates. Factor
VIII activity is expressed as a percentage (relative to normal human plasma) or preferably in IU (based on an
international standard relating to plasma factor VIII activity).
One IU of factor VIII activity is equivalent to the amount of factor VIII present in 1 mL of normal human
plasma.
Potency is determined by chromogenic method. Factor VIII plasma activity levels can be monitored by
chromogenic method or by one-stage coagulation tests.

On-demand treatment
The calculation of the necessary dose of factor VIII is based on empirical evidence that 1 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 human) x 0.5 (IU/kg per IU/dL)
The amount to be administered and the frequency of administration must always be guided by clinical
efficacy in each individual case.
In the presence of the following bleeding events, factor VIII activity should never fall below the activity
level indicated (IU/dL or % of normal human) during the corresponding period. The following table can be
used as a guide for dosage in case of bleeding episodes and surgical interventions:

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

Paediatric population
The recommended initial dosage regimen in children (from 0 to 12 years of age) is 30 to 50 IU of
AFSTYLA per kg administered 2 or 3 times a week. In children under 12 years of age, a higher
frequency of administration or the administration of higher doses may be necessary to cope with the
higher clearance rates observed in patients in this age group.
For adolescents aged 12 years or older, the recommended dosage is the same as that recommended
for adults.

Elderly patients
Clinical trials conducted with AFSTYLA did not include patients over 65 years of age.