Patient leaflet - AFSTYLA 250 IU / POWDER AND SOLVENT FOR SOLUTION FOR INJECTION/INFUSION
1. what afstyla is and what it is used for
AFSTYLA is a human clotting (coagulation) factor VIII product that is produced by recombinant DNA technology. The active substance in AFSTYLA is lonoctocog alfa.
AFSTYLA is used to treat and prevent bleeding episodes in patients with haemophilia A (inborn factor VIII deficiency). Factor VIII is involved in blood clotting. Lack of this factor means that blood does not clot as quickly as it should so there is an increased tendency to bleed. AFSTYLA works by replacing the missing factor VIII in haemophilia A patients to enable their blood to clot normally.
AFSTYLA can be used for all age groups.
2. what you need to know before you use afstyla
Do not use AFSTYLA
- if you have had an allergic reaction to AFSTYLA, or any of its ingredients (listed in
section 6).
- if you are allergic to hamster proteins.
Warnings and precautions
Traceability
It is strongly recommended that every time AFSTYLA is given, you record the date of administration, the batch number and the injected volume in your treatment diary.
Talk to your doctor, pharmacist or nurse before using AFSTYLA.
- Allergic (hypersensitivity) reactions are possible. The product contain traces of hamster proteins (see also “Do not use AFSTYLA”). If symptoms of allergic reactions occur, stop using the medicine immediately and contact your doctor. Your doctor should inform you of the early signs of allergic reactions. These include hives, generalised skin rash, tightness of the chest, wheezing, fall in blood pressure and anaphylaxis (a serious allergic reaction that causes severe difficulty in breathing, and dizziness).
- The formation of inhibitors (antibodies) is a known complication that can occur during treatment with all Factor VIII medicines. These inhibitors, especially at high levels, stop the treatment working properly and you or your child will be monitored carefully for the development of these inhibitors. If you or your child's bleeding is not being controlled with AFSTYLA, tell your doctor immediately.
- Ifyou have been told you have heart disease or are at risk for heart disease, tell your doctor or pharmacist.
- If you need a central venous access device (CVAD for injection of AFSTYLA), the risk of complications including local infections, bacteria in the blood (bacteraemia) and the formation of a blood clot in the blood vessel (thrombosis) where the catheter is inserted should be considered by your doctor.
Other medicines and AFSTYLA
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Pregnancy and breast-feeding
- 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 breast-feeding, AFSTYLA should be given only if it is clearly needed.
Driving and using machines
AFSTYLA does not affect your ability to drive and use machines.
AFSTYLA 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 could receive more than one vial. This should be taken into consideration if you are on a controlled sodium diet.
3. how to use afstyla
Your treatment should be monitored by a doctor who is experienced in the treatment of blood clotting disorders.
Always take this medicine exactly as your doctor has told you. Check with your doctor if you are not sure.
Dose
The amount of AFSTYLA you need to take and the duration of treatment depend on:
- the severity of your disease
- the site and intensity of the bleeding
- your clinical condition and response
- your body weight
Follow the directions given to you by your doctor.
Reconstitution and administration
General Instructions
- The powder must be mixed with the solvent (liquid) and withdrawn from the vial under aseptic conditions.
- AFSTYLA must not be mixed with other medicines or solvents except those mentioned in section 6.
- The solution should be clear or slightly opalescent, yellow to colourless, i.e., it might be sparkling when held up to the light but must not contain any obvious particles. After filtering or withdrawal (see below) the solution should be checked by eye, before it is used. Do not use the solution if it is visibly cloudy or if it 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.
Reconstitution and administration
Without opening the vials, warm the AFSTYLA powder and the liquid to room or body temperature. This can be done either by leaving the vials 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 °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 (which contnains the filter transfer device), then follow the instructions given below.
| 1 | 1. Open the Mix2Vial by peeling off the lid. Do not remove the Mix2Vial from the blister package! | |
| CEjm | 2 | 2. Place the solvent vial on an even, clean surface and hold the vial tight. Take the Mix2Vial together with the blister package and push the spike of the blue adapter end straight down through the solvent vial stopper. |
| LJ 3 | 3. Carefully remove the blister package from the Mix2Vial set by holding at the rim, and pulling vertically upwards. Make sure that you only pull away the blister package and not the Mix2Vial set. |
| M LJ 4 | 4. Place the powder vial on an even and firm surface. Invert the solvent vial with the Mix2Vial set attached and push the spike of the transparent adapter end straight down through the powder vial stopper. The solvent will automatically flow into the powder vial. |
| eg LJ 5 | 5. With one hand grasp the product-side of the Mix2Vial set and with the other hand grasp the solvent-side and unscrew the set carefully counterclockwise into two pieces. Discard the solvent vial with the blue Mix2Vial adapter attached. |
| — 6 | 6. Gently swirl the product vial with the transparent adapter attached until the substance is fully dissolved. Do not shake. |
| J t— 7 | 7. Draw air into an empty, sterile syringe. While the product vial is upright, connect the syringe to the Mix2Vial's Luer Lock fitting by screwing clockwise. Inject air into the product vial. |
Withdrawal and administration
| ® 8 | 8. While keeping the syringe plunger pressed, turn the system upside down and draw the solution into the syringe by pulling the plunger back slowly. |
9
9. Now that the solution has been transferred into the syringe, firmly hold on to the barrel of the syringe (keeping the syringe plunger facing down) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing counterclockwise.
Use the venipuncture kit supplied with the product, insert the needle into a vein. Let blood flow back to the end of the tube. Attach the syringe to the threaded, locking end of the venipuncture kit. Inject the reconstituted solution slowly (as comfortable for you, up to a maximum of 10 ml/min) into the vein following the instructions given to you by your doctor. Take care not to get any blood in the syringe containing the product.
Check yourself for any side effects that might happen straight away. If you have any side effects that might be related to the administration of AFSTYLA, the injection should be stopped (see also section 2).
Use in children and adolescents
AFSTYLA can be used in children and adolescents of all ages. In children below the age of 12 higher doses or more frequent injections may be needed. Children above 12 years of age can use the same dose as adults.
If you use more AFSTYLA than you should
If you have injected more AFSTYLA than you should, please inform your doctor.
If you forget to use AFSTYLA
Do not take a double dose to make up for a forgotten dose. Proceed with the next dose immediately and continue as advised by your doctor or pharmacist.
If you stop using AFSTYLA
If you stop using AFSTYLA you may no longer be protected against bleeding or a current bleed may not stop. Do not stop using AFSTYLA without consulting your doctor.
If you have any further questions on the use of 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.
Please stop using the medicine immediately and contact your doctor if:
- you notice symptoms of allergic reactions
Allergic reactions may include the following symptoms: hives, generalised urticaria (itchy rash), tightness of the chest, difficulty in breathing, wheezing, low blood pressure, dizziness, and anaphylaxis. If this happens, you should stop using the medicine immediately and contact your doctor.
- you notice that the medicine stops working properly (bleeding is not stopped)
For children not previously treated with Factor VIII medicines, inhibitor antibodies (see secion 2) may form very commonly (more than 1 in 10 patients); however patients who have received previous treatment with Factor VIII (more than 150 days of treatment) the risk is uncommon (less than 1 in 100 patients). If this happens your medicine may stop working properly and you may experience persistent bleeding. If this happens, you should contact your doctor immediately.
Common side effects (may affect up to 1 in 10 users)
- allergic reaction
- dizziness
- tingling or numbness (paraesthesia)
- rash
- fever
Uncommon side effects (may affect up to 1 in 100 users)
- itching
- redness of the skin
- pain at the injection site
- chills
- feeling hot
Side effects in children and adolescents
No age-specific differences in adverse reactions were observed between children, adolescents and adult subjects.
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 via the UK Yellow Card system.
Website:or search for MHRA Yellow Card in the Google Play or Apple App Store
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 carton.
- Store in a refrigerator (2 °C to 8 °C).
- Before the AFSTYLA powder is reconstituted it may be kept at room temperature (below 25 °C) for a single period not exceeding 3 months, within the expiration date printed on the cartons and the vials. Please record the date from when you start to store AFSTYLA at room temperature on the product carton.
- Once the product has been taken out of the refrigerator, the product must not be returned to the refrigerator.
- Do not freeze.
- Keep the vial in the outer carton in order to protect from light.
- The reconstituted product should preferably be used immediately.
- If the reconstituted product is not administered immediately, storage times and
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 last paragraph of section 2), sucrose.
Solvent: Water for injections.
What AFSTYLA looks like and contents of the pack
AFSTYLA is presented as white or slightly yellow powder or friable mass and clear, colourless solvent for solution for injection.
The reconstituted solution should be clear to slightly opalescent, yellow to colourless i.e., it might sparkle when held up to the light but must not contain any obvious particles.
Presentations
One pack with 250, 500 or 1000 IU containing:
1 vial with powder
1 vial with 2.5 ml water for injections
1 filter transfer device 20/20
One inner box containing:
1 disposable 5 ml syringe
1 venipuncture set
2 alcohol swabs
1 non- sterile plaster
One pack with 1500, 2000, 2500 or 3000 IU containing:
1 vial with powder
1 vial with 5 ml water for injections
1 filter transfer device 20/20
One inner box containing:
1 disposable 10 ml syringe
1 venipuncture set
2 alcohol swabs
1 non- sterile plaster
Not all pack sizes may be marketed.
Immediate containers
| 250 IU | Glass vial with a rubber stopper, an orange plastic disc, and a green striped aluminium cap |
| 500 IU | Glass vial with a rubber stopper, a blue plastic disc, and a green striped aluminium cap |
| 1000IU | Glass vial with a rubber stopper, a green plastic disc, and a green striped aluminium cap |
| 1500IU | Glass vial with a rubber stopper, a turquoise plastic disc, and a green striped aluminium cap |
| 2000IU | Glass vial with a rubber stopper, a purple plastic disc, and a green striped aluminium cap |
| 2500IU | Glass vial with a rubber stopper, a light grey plastic disc, and a green striped aluminium cap |
| 3000IU | Glass vial with a rubber stopper, a yellow plastic disc, and a green striped aluminium cap |
Marketing Authorisation Holder and Manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
35041 Marburg
Germany
For any information about this medicine, please contact the local representative of the
Marketing Authorisation Holder:
CSL Behring UK Ltd.
Tel: +44 (0)1444 447405
This leaflet was last revised in 10/2019.
Detailed information on this medicine is available on the European Medicines Agency web site:
The following information is intended for healthcare professionals only:
Treatment monitoring
During the course of treatment, appropriate determination of factor VIII levels is advised to guide the dose to be administered and the frequency of repeated injections. Individual patients may vary in their responses to factor VIII, demonstrating different half-lives and recoveries. Dose based on bodyweight may require adjustment in underweight or overweight patients. In the case of major surgical interventions in particular, precise monitoring of the substitution therapy by means of coagulation analysis (plasma factor VIII activity) is indispensable.
When using an in vitro thromboplastin time (aPTT)-based one stage clotting assay for determining factor VIII activity in patients’ blood samples, plasma factor VIII activity results can be significantly affected by both the type of aPTT reagent and the reference standard used in the assay. Also there can be significant discrepancies between assay results obtained by aPTT-based one stage clotting assay and the chromogenic assay according to Ph. Eur. This is of importance particularly when changing the laboratory and/or reagents used in the assay.
Plasma factor VIII activity in patients receiving AFSTYLA using either the chromogenic assay or the one-stage clotting assay should be monitored to guide the dose administered and the frequency of repeat injections. The chromogenic assay result most accurately reflects the clinical haemostatic potential of AFSTYLA and is preferred. The one-stage clotting assay result underestimates the factor VIII activity level compared to the chromogenic assay result by approximately 45%. If the one-stage clotting assay is used, multiply the result by a conversion factor of 2 to determine the patient’s factor VIII activity level.
Posology
The dose and duration of the substitution therapy depend on the severity of the factor VIII deficiency, on the location and extent of the bleeding and on the patient's clinical condition.
The number of units of factor VIII administered is expressed in International Units (IU), which are related to the current WHO concentrate standard for factor VIII products. Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or in preferably International Units (relative to an International Standard for factor VIII in plasma).
One International Unit (IU) of factor VIII activity is equivalent to that quantity of factor VIII in one ml of normal human plasma.
Potency assignment is determined using a chromogenic substrate assay.
Plasma factor VIII levels can be monitored using either a chromogenic substrate assay or a one-stage clotting assay.
On demand treatment
The calculation of the required dose of factor VIII is based on the empirical finding that 1 International Unit (IU) factor VIII per kg body weight raises the plasma factor VIII activity by 2 IU/dl. The required dose is determined using the following formula:
Dose (IU) = body weight (kg) x Desired factor VIII rise (IU/dl or % of normal) x 0.5 (IU/kg per IU/dl)
The amount to be administered and the frequency of administration should always be oriented to the clinical effectiveness in the individual case.
In the case of the following haemorrhagic events, the factor VIII activity should not fall below the given plasma activity level (in % of normal or IU/dl) within the corresponding period. The following table can be used to guide dosing in bleeding episodes and surgery:
| Degree of haemorrhage / Type of surgical procedure | Factor VIII level required (%) (IU/dl) | Frequency of doses (hours) / Duration of therapy (days) |
| Haemorrhage | ||
| Early haemarthrosis, muscle bleeding or oral bleeding | 20 –40 | Repeat injection every 12 to 24 hours. At least 1 day, until the bleeding episode as indicated by pain is resolved or healing is achieved. |
| More extensive haemarthrosis, muscle bleeding or haematoma | 30 – 60 | Repeat injection every 12 to 24 hours for 3–4 days or more until pain and acute disability are resolved. |
| Life threatening haemorrhages | 60 – 100 | Repeat injection every 8 to 24 hours until threat is resolved. |
| Surgery | ||
| Minor surgery including tooth extraction | 30 – 60 | Inject every 24 hours, at least 1 day, until healing is achieved. |
| Major surgery | 80 – 100 (pre- and postoperative) | Repeat injection every 8 to 24 hours until adequate wound healing, then therapy for at least another 7 days to maintain a factor VIII activity of 30% to 60% (IU/dl). |
Prophylaxis
The recommended starting regimen is 20 to 50 IU/kg of AFSTYLA administered 2 to 3 times weekly. The regimen may be adjusted based on patient response.
Paediatric population
The recommended starting regimen in children (0 to <12 years of age) is 30 to 50 IU per kg of AFSTYLA administered 2 to 3 times weekly. More frequent or higher doses may be required in children <12 years of age to account for the higher clearance in this age group. For adolescents of 12 years of age and above, the dose recommendations are the same as for adults.
Elderly
Clinical studies of AFSTYLA did not include subjects over 65 years of age.
10