CSL Behring

Powder and solvent for solution for injection 250 IU 
(White or yellowish powder or brittle mass and clear, colorless liquid)

Read all of this leaflet carefully before you start using this medicine. It contains information that is important to you.

  • Save this information, you may need to read it again.
  • If you have any further questions, ask your doctor, pharmacist or nurse.
  • This medicine has been prescribed for you only. Do not give it to others. It can harm them, even if they show signs of illness similar to yours.
  • If you get any side effects , talk to your doctor, pharmacist or nurse. This also applies to any side effects not mentioned in this information. See section 4.

In this leaflet: 
1. What AFSTYLA is and what it is used for 
2. What you need to know before using AFSTYLA 
3. How to use AFSTYLA 
4. Possible side effects 
5. How to store AFSTYLA 
6. Contents of the packaging and other information 

1. What STYLE is and what it is used for

AFSTYLA is a human coagulation factor (clotting factor) VIII product produced by recombinant DNA technology. The active substance in AFSTYLA is lonoktokog alfa.

STYLING is used to treat and prevent bleeding in patients with hemophilia A (congenital factor VIII deficiency). Factor VIII is needed for blood clotting. Lack of this factor means that blood cannot clot as quickly as it should and therefore there is an increased tendency to bleed. STYLING works by replacing the missing factor VIII in patients with hemophilia A so that their blood can clot normally.

AFSTYLA is suitable for use in all age groups.

2. What you need to know before using STYLE

Do not use STYLE

  • if you have had an allergic reaction to AFSTYLA, or any of the excipients (listed in section 6).
  • if you are allergic to hamster protein.

Warnings and cautions

Traceability

It is strongly recommended that you record the date of administration, the batch number, and the injected volume in a treatment diary each time AFSTYLA is given.

Talk to a doctor, pharmacist, or nurse before using AFSTYLA.

  • Allergic hypersensitivity reactions may occur. The product contains traces of hamster proteins (see also “Do not use STYLE”). If symptoms of allergic reactions occur, stop using the medicine immediately, and contact your doctor. Your doctor should inform you of early signs of allergic reactions. These include hives, generalized urticaria, chest tightness, wheezing, drop in blood pressure, and anaphylaxis (a severe allergic reaction that causes severe difficulty breathing and dizziness).
  • The development of inhibitors ( antibodies ) is a known complication that may occur during treatment with any factor VIII drug. The inhibitors prevent, especially at high levels, that the treatment works properly. You or your child will be closely monitored for the development of such inhibitors. If you or your child has a hemorrhage that cannot be controlled with AFSTYLA, tell your doctor immediately.
  • If you have been told by your heart that you have a heart condition or are at risk for heart disease, tell your doctor or pharmacist.
  • If you need a central venous catheter (CVK for injection of AFSTYLA), the risk of complications such as local infections, bacteria in the blood (bacteremia), and the formation of blood clots in the blood vessel ( thrombosis ) where the catheter is located should be considered by a doctor.

Other drugs and STYLE

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 or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
  • During pregnancy and lactation, STYLY should only be given if absolutely necessary.

Driving and using machines

AFSTYLA does not affect the ability to drive or use machines.

STYLING contains sodium

AFSTYLA contains up to 7 mg (0.3 mmol) sodium per ml after reconstitution.

However, depending on your body weight and your dose of AFSTYLA, you may receive more than one vial. This should be considered if you have been prescribed a low-salt diet.

3. How to use STYLE

Your treatment should be done under the supervision of a doctor who has experience in the treatment of bleeding disorders.

Always use this medicine exactly as your doctor has told you. If you are not sure, talk to your doctor.

Dosage

The amount of STYLING you need and the treatment time depend on:

  • the severity of your illness
  • where it bleeds and to what extent
  • your clinical condition and treatment response
  • your body weight

Follow your doctor’s instructions.

Preparation and administration

General instructions

  • The powder should be mixed with the diluent and withdrawn from the vial under aseptic conditions.
  • AFSTYLA must not be mixed with other medicinal products or liquids other than those mentioned in section 6.
  • The solution should be clear or slightly opalescent (yellow translucent), yellow to colorless, ie, it may glow if held up to the light but must not contain any visible particles. After filtering or filling the syringe (see below), the solution should be visually inspected before use. Do not use the solution if it looks cloudy or contains flakes or particles.
  • Any unused product or waste material should be disposed of in accordance with local requirements and as instructed by your doctor.

Preparation and administration

Before opening the vials, WARRANT powder and liquid to room temperature or body temperature. This can be done either by allowing the bottles to stand 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 must not be heated above body temperature (37 ºC).

Carefully remove the plastic lids from the bottles and clean the surfaces of the rubber stoppers with an alcohol wipe. Allow the vials to dry before opening the Mix2Vial package (which contains the transfer kit with filter). Then follow the instructions below.

1
1. Open the Mix2Vial by pulling off the cover. Do notremove Mix2Vial from the blister pack!
2 2. Place the vial of solvent on a flat, clean surface and hold the bottle firmly. Take Mix2Vial with the blister pack and push the tip of the blue adapter part straight down through the vial stopper.
3 Carefully remove the blister pack from the Mix2Vial set by grasping the edge and pulling straight up. Make sure that only the blister pack is removed, not the Mix2Vial set.
4 4. Place the vial of powder on a flat, firm surface. Invert the liquid bottle with the attached Mix2Vial set and push the tip of the transparent adapter part straight down through the stopper of the powder bottle. The liquid will automatically flow over to the powder bottle.
 5 5. Grasp the part of the Mix2Vial set where the powder bottle is located with one hand and grasp the part where the liquid bottle is with the other hand and carefully unscrew the set counterclockwise into 2 parts.Dispose of the liquid bottle with the blue Mix2Vial part attached.
 6 Carefully rotate the vial of the product with the attached transparent adapter until the powder is completely dissolved. Do not shake the bottle.

 7
7. Inhale air into an empty, sterile syringe . While the product vial is upright, the syringe is connected to the Luer lid fitting on the Mix2Vial part by turning clockwise. Inject air into the bottle.

Commissioning and administration

 8 8. While holding down the syringe plunger, turn the bottle upside down along with the set and syringe . Pull the solution into the syringe by slowly returning the plunger.
 9 9. Once all the solution has been transferred to the syringe, grasp the syringe firmly (hold the syringe with the plunger down) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing it counterclockwise.

Use the supplied venipuncture set and insert the needle into a vein. Let the blood flow back to the end of the tube. Attach the syringe to the threaded locking device at the end of the venipuncture set. Slowly inject the reconstituted solution into the vein (as convenient for you, up to a maximum of 10 ml/min) according to the instructions given to you by your doctor. Be careful not to get any blood into the syringe with a reconstituted solution.

Find out if you get any immediate side effects. If you experience any side effects that may be due to the administration of AFSTYLA, the injection should be discontinued (see also section 2).

Use in children and adolescents

STYLING can be used for children and young people of all ages. In children (under 12 years of age), higher doses or more frequent injections may be needed. Children over 12 years of age can use the same dose as adults.

If you use too much OFF  

If you have injected more STYLING than you should tell your doctor.

If you have forgotten to use STYLE

Do not take a double dose to make up for a forgotten dose. Take the next dose immediately and continue according to your doctor’s prescription.

If you stop using AFSTYLA

If you stop using AFSTYLA, you may no longer be protected from bleeding or ongoing bleeding may not stop. Do not stop using AFSTYLA without consulting a doctor or pharmacist.

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

4. Possible side effects

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

Stop taking the medicine immediately and contact your doctor immediately if:

  • you get symptoms of an allergic reaction
  • Allergic reactions may include the following symptoms: hives, generalized urticaria (itchy rash), pressure over the chest, difficulty breathing, wheezing, low blood pressure, dizziness, and anaphylaxis. If this happens, stop using the medicine immediately and consult a doctor.
  • if you notice that the medicine is not working properly (bleeding does not stop) 
    For children who have not been treated with factor VIII before, inhibitory antibodies may be formed (see section 2). This complication is classified as very common (affects more than 1 user in 10). However, the risk is classified as uncommon (occurs in less than 1 in 100 users) in patients who have previously been treated with factor VIII (treatment more than 150 days). If this happens, your or your child’s medication may stop working properly and you or your child may experience persistent bleeding. Contact a doctor immediately if this happens.

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

  • Allergic reaction
  • Dizziness
  • Tingling or numbness ( paresthesia )
  • Rash
  • Fever

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

  • Itching
  • Reddening of the skin
  • Injection site pain
  • Freezing breaks
  • Feel warm

Side effects are in children and adolescents

No age-specific differences in adverse reactions were observed between children, adolescents, and adult patients.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Medical Products Agency, www.lakemedelsverket.se. By reporting side effects, you can help increase drug safety information. 

5. How to STORE STYLE

  • 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 carton (after EXP).
  • Store in a refrigerator (2 ° C-8 ° C).
  • Before preparation can AFSTYLA powder is stored at room temperature (below 25 ° C) for a continuous period exceeding 3 months and before the expiration date on the carton and the vials. Make a note of the date on the outer carton when you start storing AFSTYLA at room temperature.
  • Once the package has been removed from the refrigerator, the product must not be put back in the refrigerator.
  • Do not freeze.
  • Keep the vial in the outer carton. Sensitive to light.
  • The finished product should preferably be used immediately.
  • If the finished product is not administered immediately, the storage time and conditions before use are the responsibility of the user.

6. Contents of the packaging and other information

Content declaration

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 lonoktokog alfa.

500 IU per vial; after reconstitution with 2.5 ml of water for injections, the solution contains 200 IU / ml of lonoktokog alfa.

1000 IU per vial; after reconstitution with 2.5 ml of water for injections, the solution contains 400 IU / ml of lonoktokog alfa.

1500 IU per vial; after reconstitution with 5 ml of water for injections, the solution contains 300 IU / ml of lonoktokog alfa.

2000 IU per vial; after reconstitution with 5 ml of water for injections, the solution contains 400 IU / ml of lonoktokog alfa.

2500 IU per vial; after reconstitution with 5 ml of water for injections, the solution contains 500 IU / ml of lonoktokog alfa.

3000 IU per vial; after reconstitution with 5 ml of water for injections, the solution contains 600 IU / ml of lonoktokog alfa.

Other ingredients are:

L-histidine, polysorbate 80, calcium chloride dihydrate, sodium chloride (see the last paragraph of section 2), sucrose.

Diluent: Water for injections.

What the medicine looks like and the contents of the pack

AFSTYLA is a white or yellowish powder or brittle mass and clear, colorless solution for injection.

The reconstituted solution should be clear or slightly opalescent, yellow to colorless, ie it may glisten if held against the light, but it must not contain any visible particles.

Packaging designs

A pack of 250, 500, or 1000 IU contains:

1 vial of powder

1 vial with 2.5 ml of water for injections

1 transfer set with filter 20/20

The inner carton contains:

1 disposable syringe 5 ml

1 venipuncture set

2 alcohol dryers

1 non-sterile patch

A pack of 1500, 2000, 2500, or 3000 IU contains:

1 vial of powder

1 vial with 5 ml water for injections

1 transfer set with filter 20/20

The inner carton contains:

1 disposable syringe 10 ml

1 venipuncture set

2 alcohol dryers

1 non-sterile patch

Inner packaging

250 IU Vial made of glass with a rubber stopper, an orange cap and a green striped aluminum seal
500 IU Vial made of glass with a rubber stopper, a blue cap and a green striped aluminum seal
1000 IU Vial made of glass with a rubber stopper, a green cap and a green striped aluminum seal
1500 IU Vial made of glass with a rubber stopper, a turquoise cap and a green striped aluminum seal
2000 IU Vial made of glass with a rubber stopper, a purple cap and a green striped aluminum seal
2500 IU Vial made of glass with a rubber stopper, a light gray cap and a green striped aluminum seal
3000 IU Vial made of glass with a rubber stopper, a yellow cap and a green striped aluminum seal

Marketing Authorization Holder and Manufacturer

CSL Behring GmbH

Emil-von-Behring- Straße 76

35041 Marburg

Germany

Belgium / Belgique / BelgienCSL Behring NVTel: +32 15 28 89 20 LithuaniaCSL Behring GmbHTel: +49 69 30584437
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DenmarkCSL Behring ABTel: +46 8 544 966 70 MaltaAM Mangion Ltd.Tel: +356 2397 6333
GermanyCSL Behring GmbHTel: +49 69 30584437 The NetherlandsCSL Behring BVTel: + 31 85 111 96 00
EestiCSL Behring GmbHTel: +49 69 30584437 NorwayCSL Behring ABTel: +46 8 544 966 70
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FranceCSL Behring SATel: + 33 – (0) -1 53 58 54 00 PortugalCSL Behring LdaTel: +351 21 782 62 30
CroatiaMarti Farm dooTel: +385 1 5588297 RomaniaPrisum International Trading srlTel: +40 21 322 0171
IrelandCSL Behring GmbHTel: +49 69 30517254 SloveniaMediSanus dooTel: +386 1 25 71 496
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ItalyCSL Behring SpATel: +39 02 34964 200 Finland / FinlandCSL Behring ABPuh / Tel: +46 8 544 966 70
ΚύπροςCSL Behring ΕΠΕ:Ηλ: +30 210 7255 660
LatviaCSL Behring GmbHTel: +49 69 30584437 United KingdomCSL Behring UK Ltd.Tel: +44 1444 447405

This leaflet was last amended on 10/2019.

Further information on this medicine is available on the European Medicines Agency

The following information is intended for healthcare professionals only:

Treatment monitoring

During treatment, determination of factor VIII levels is recommended as a guide for adjusting the dose and dosing intervals for repeated infusions. Individual patients’ responses to factor VIII can vary, showing different half-lives and different levels of the so-called recovery. Dose based on body weight may need to be adjusted in underweight or obese patients. Particularly in the case of major surgical procedures, close monitoring of substitution treatment by coagulation assay ( factor VIII activity in plasma ) is essential.

Using an in vitro thromboplastin time (aPTT) -based one-step coagulation test to determine the factor VIII activity in the patient’s blood sample, the factor VIII activity in plasma can be significantly affected by both the type of aPTT reagent and the reference standard used in the assay. According to Ph. Eur, there may also be significant discrepancies between the assay results obtained from an aPTT-based one-step coagulation assay and chromogenic assay. This is especially important when changing the laboratory and/or reagents used in the assay.

The plasma factor VIII activity in patients receiving AFSTYLA should be monitored using either a chromogenic assay or a one-step coagulation test to obtain guidance on the dose to be administered and the intervals for repeated injections. Results from chromogenic analysis reflect the clinical hemostatic potential of AFSTYLA most accurately and are preferred. Results from one-step coagulation tests underestimate the factor VIII activity level compared to results from the chromogenic analysis by about 45%. If a one-step coagulation test is used, multiply the result by the conversion factor 2 to determine the patient’s factor VIII activity level.

Dosage

The dose and duration of substitution treatment depend on the severity of the factor VIII deficiency, the location and extent of the bleeding, and the patient’s clinical condition.

The number of factor VIII units administered is specified in International Units (IU), which is related to the current WHO concentrate standard for factor VIII products. The factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma ) or preferably in International Units (relative to an international standard for factor VIII in plasma ).

An International Unit (IU) factor VIII activity is equivalent to the amount of factor VIII present in one ml of normal human plasma.

Allocation of strength is determined using chromogenic substrate analysis.

Factor VIII levels in plasma can be monitored using either chromogenic substrate assay or one-stage clotting assay.

Treatment if necessary

The calculation of the appropriate dose of factor VIII is based on the empirical finding that 1 International Unit (IU) factor VIII per kg body weight increases the factor VIII activity in plasma by 2 IU / dl.

The following formula can be used to calculate the appropriate dose:

Dose (IU) = body weight (kg) x desired increase of factor VIII (IU / dl or% of normal value) x 0.5 (IU / kg per IU / dl)

The dose administered and the dosing interval should always be adapted to the clinical effect in each individual case.

Bleeding rate / Type of surgery Appropriate factor VIIIlevel(% or IU / dl) Dosage interval (hours) /Treatment period (days)
Bleeding

Early osteoarthritis, muscle bleeding or oralbleeding 20 – 40 Repeat injection every 12 to 24 hours. At least one day, until the bleeding episode, detected by pain) ceased or healing was achieved.
More extensive osteoarthritis, muscle bleeding, or hematoma 30 – 60 Repeat injection every 12 to 24 hours for 3-4 days or longer, until pain and acute movement restriction have been lifted.
Life-threatening bleeding 60 – 100 Repeat injection every 8 to 24 hours until the critical condition is lifted.
Surgery

Minor surgeries including tooth extraction 30 – 60 Inject every 24 hours for at least 1 day, until healing is achieved.
Major surgeries 80 – 100(pre- and postoperatively) Repeat the injection every 8 to 24 hours until adequate wound healing is achieved, then continue treatment for at least another 7 days to maintain factor VIIIactivity between 30% and 60% (IU / dl).

Prophylaxis

The recommended starting dose of AFSTYLA is 20 to 50 IU / kg administered 2 to 3 times a week. The treatment regimen can be adjusted based on the patient’s response.

Pediatric population

The recommended starting dose of AFSTYLA in children (0 to <12 years) is 30 to 50 IU per kg administered 2 to 3 times a week. For children under 12 years of age, shorter dosing intervals or higher doses may be necessary to compensate for higher clearance in this age group.

For adolescents from 12 years of age, dosing recommendations are the same as for adults.

Older

Clinical trials of AFSTYLA did not include people over 65 years of age.

Muhammad Nadeem

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