250 IU / 2 ml, 500 IU / 2 ml, 1000 IU / 2 ml of powder and solvent for injection, solution
rurioktokog alpha pegol (pegylated recombinant human coagulation factor VIII)
1. What ADYNOVI is and what it is used for
ADYNOVI contains the active substance rurioctococcal alpha pegol, pegylated human coagulation factor VIII. The human coagulation factor VIII has been modified to last longer. Factor VIII is needed for the blood to coagulate and stop bleeding. In patients with hemophilia A (congenital factor VIII deficiency ), factor VIII is missing or does not work normally.
ADYNOVI is used to treat and prevent bleeding in patients from the age of 12 with hemophilia A (a hereditary form of hemophilia caused by a factor VIII deficiency ).
2. What you need to know before using ADYNOVI
Do not use ADYNOVI
- if you are allergic to rurioktokog alfa pegol, oktokog alfa, or any of the other ingredients of this medicine (listed in section 6)
- if you are allergic to mouse or hamster proteins.
Consult a doctor if you are unsure.
Warnings and cautions
Talk to your doctor before using ADYNOVI.
There is a small risk that you may get an anaphylactic reaction (a severe, sudden allergic reaction ) when you use ADYNOVI. You should know the early signs of allergic reactions such as rash, hives, general itching, swelling of the lips and tongue, difficulty breathing, wheezing, chest tightness, general malaise, and dizziness. These may be early symptoms of anaphylactic shock. Other symptoms may include severe dizziness, unconsciousness and extreme difficulty breathing.
If any of these symptoms occur, stop the injection immediately and consult a doctor. Severe symptoms, including difficulty breathing and (almost) fainting, require immediate urgent treatment.
If you suffer from heart disease, tell your doctor about this, as there is an increased risk of complications related to coagulation (the ability of the blood to clot).
Patients developing factor VIII inhibitors
The development of inhibitors ( antibodies ) is a known complication that can occur during treatment with any factor VIII drug. The inhibitors prevent the treatment from working properly, especially at high levels. You or your child will be closely monitored for the development of inhibitors. If you or your child suffer from bleeding that cannot be controlled with ADYNOVI, tell your doctor immediately.
Complications related to catheters
If you need a central venous catheter (CVAD), your doctor should consider the risk of CVAD-related complications, including local infections, the presence of bacteria in the blood, and blood clots at the catheter site.
Children and young people
ADYNOVI can only be used in adolescents and adults (12 years and older). The information about warnings and precautions also applies to young people.
Other medicines and ADYNOVI
Tell your doctor 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 for advice before using this medicine. Hemophilia A is rare in women. Therefore, there is no experience with the use of ADYNOVI during pregnancy and lactation.
Driving and using machines
ADYNOVI has no effect on the ability to drive and use machines.
ADYNOVI contains sodium
This medicine contains 0.45 mmol sodium (10 mg) per vial. This should be taken into consideration for patients prescribed a low-salt diet
3. How to use ADYNOVI
Treatment with ADYNOVI will be initiated and supervised by a physician experienced in the management of patients with hemophilia A.
Your doctor will calculate the dose of ADYNOVI that is right for you depending on your condition, your weight, and whether it is used to prevent or treat bleeding. How often the treatment is given depends on how well ADYNOVI works for you. Replacement treatment with ADYNOVI is usually a lifelong treatment.
Always use this medicine exactly as your doctor has told you. Ask your doctor if you are unsure.
Prevention of bleeding
The usual dose of ADYNOVI is 40 to 50 IU per kg body weight administered twice a week.
Treatment of bleeding
Dose one of ADYNOVI is calculated based on your body weight and the factor VIIIlevels to be achieved. The target levels for factor VIII depend on the severity of the bleeding and its occurrence.
Talk to your doctor if you think the effect of ADYNOVI is not enough.
Your doctor will perform appropriate laboratory tests to ensure that you have the correct factor VIII level. This is especially important if you are having major surgery.
Use for children and adolescents
ADYNOVI can only be used for adolescents and adults (12 years and older). Dose one for adolescents is also calculated by body weight and is the same as for adults.
How ADYNOVI is given
ADYNOVI is usually injected into a vein ( intravenously ) by a doctor or nurse. You or someone else can also administer ADYNOVI as an injection, but only after the necessary training. Detailed instructions on how to give yourself the medicine can be found at the end of this leaflet.
If you use more ADYNOVI than you should
Always use ADYNOVI exactly as your doctor has told you. Consult a doctor if you are unsure. If you have been given more ADYNOVI than recommended, talk to your doctor as soon as possible.
If you forget to use ADYNOVI
Do not take a double dose to make up for a forgotten dose. Take the next dose as planned and continue according to your doctor’s prescription.
If you stop using ADYNOVI
Do not stop using ADYNOVI without consulting your doctor.
If you have any further questions on the use of this product, ask your doctor.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
A sudden and severe allergic reaction (anaphylactic shock ) must injection stopped immediately. If you get any of the following early symptoms of an allergic reaction, contact your doctor immediately :
- rash, hives, general itching
- swelling of the lips and tongue
- difficulty breathing, wheezing, pressure over the chest
- general malaise
- dizziness and unconsciousness.
Severe symptoms, including difficulty breathing and (almost) fainting, require immediate urgent treatment.
In patients previously treated with factor VIII (more than 150 days of treatment), inhibitory antibodies (inhibitors) may be formed (see section 2). This complication is classified as uncommon (affects less than 1 user in 100). If this happens, your medication may stop working properly and you may experience persistent bleeding. Contact a doctor immediately if this happens.
Common side effects are (may affect up to 1 in 10 people)
Headache, nausea, diarrhea, rash
Less common side effects are (may affect up to 1 in 100 people)
Redness, allergic reaction (hypersensitivity)
Antibodies (inhibitors) to factor VIII (in patients who have previously received factor VIII treatment (more than 150 days of treatment))
Additional side effects in children
The frequency, type, and severity of side effects in children are expected to be the same as in adults.
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 ADYNOVI
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. The expiration date is the last day of the specified month.
Store in a refrigerator (2 ° C – 8 ° C).
Do not freeze.
Store the blister pack in the outer carton. Sensitive to light.
During the shelf life, the powder vial can be stored at room temperature (up to 30 ° C) for a maximum continuous period of 3 months. The expiry date for the medicine is then the end of this 3-month period, or alternatively the expiry date which is stated on the vial, whichever is the earlier. Note the end date of the 3-month period on the outer carton. The drug must not be stored in a refrigerator after it has been stored at room temperature. The solution must not be stored in the refrigerator after reconstitution.
Use the medicine within 3 hours after the powder has completely dissolved.
This medicine is for single use only. Dispose of the remaining solution appropriately.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. Contents of the packaging and other information
Content declaration
- The active substance is rurioctococcal alpha pegol (pegylated human coagulation factor VIII produced by recombinant DNA technology). Each vial of powder nominally contains 250, 500, or 1000 IU rurioctococcal alpha pegol.
- The solution for injection contains 2 ml of sterile water for injections.
- The other ingredients are mannitol, trehalose dihydrate, histidine, glutathione, sodium chloride, calcium chloride dihydrate, tris (hydroxymethyl) aminomethane, polysorbate 80. ADYNOVI contains sodium, see section 2.
What the medicine looks like and contents of the pack
ADYNOVI is supplied as a powder and solvent for solution for injection. The powder is white to an off-white granular powder. The solution liquid is a clear and colorless solution. After reconstitution, the solution is clear, colorless, and free of foreign particles.
Marketing Authorization Holder and Manufacturer
Salesman
Baxalta Innovations GmbH
Industriestrasse 67
A-1221 Vienna
Tel: +44 (0) 1256 894 959
Email: medinfoEMEA@shire.com
Manufacturer
Baxalta Belgium Manufacturing SA
Boulevard René Branquart 80
B ‑ 7860 Lessines
Belgium
This leaflet was last modified 03/2018
Other sources of information
Further information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu/
The following information is intended for healthcare professionals only:
Instructions for preparation and administration
ADYNOVI must not be mixed with any other medicinal product or solvent.
It is strongly recommended that the name and batch number of the medicine be recorded each time ADYNOVI is given. Detachable labels are on the blister pack.
Instructions for preparation
- Do not use this medicine after the expiry date which is stated on the labels and carton.
- Do not use unless the blister lid is completely closed
- The solution must not be stored in the refrigerator after reconstitution.
- If the medicine is still stored in a refrigerator: remove the closed blister (containing vials of powder and solvent combined with the reconstitution system) from the refrigerator and allow it to reach room temperature (between 15 ° C and 25 ° C).
- Wash your hands thoroughly with soap and warm water.
- Open the blister pack with ADYNOVI by pulling off the top. Remove the BAXJECT III system from the blister.
- Place the powder vial on a flat surface with the solvent vial on top (Fig. 1). The solvent vial has a blue stripe. Do not remove the blue cap until instructed to do so at a later stage.
- Hold the powder vial in the BAXJECT III system with one hand and firmly push the solvent vial down with the other hand until the system is fully compressed and the solvent drains into the powder vial (Fig. 2). Do not tilt the system until all the solvent has drained into the powder vial.
- Check that all solvent has been transferred. Gently swirl the bottle until all the powder has dissolved (Fig. 3). Make sure that the powder is completely dissolved, otherwise not all prepared solution can pass through the filter. The drug dissolves rapidly (usually in less than 1 minute). After reconstitution, the solution should be clear, colorless, and free of foreign particles.
Instructions for injection
The aseptic technique (very clean conditions) must be used during the injection.
NOTE!
- Inspect the reconstituted solution for particles and discoloration before injection(the solution should be clear, colorless, and free from particles). The medicine must not be used if the solution is not completely clear or if the powder has not completely dissolved.
- Remove the blue cover from the BAXJECT III. Do not draw air into the syringe. Connect the syringe to the BAXJECT III. The use of a syringe with a Luer cap is recommended.
- Turn the system upside down (so that the powder vial is on top). Withdraw the reconstituted solution into the syringe by slowly withdrawing the plunger.
- Disconnect the syringe and then attach a butterfly needle to it and inject the reconstituted solution into a vein. The solution should be administered slowly, at a rate that is determined by the patient’s comfort level but does not exceed 10 ml per minute. (See section 4 “Possible side effects”).
- Dispose of the remaining solution appropriately.
The following information is intended for healthcare professionals only:
Treatment if necessary
The calculation of the required dose of factor VIII has based on the empirical finding that 1 IU factor VIII per kg body weight increases the activity of factor VIII in plasma by 2 IU / dl. The required dose is determined using the following formula. The table below can be used as a guide for dosing during bleeding episodes and surgical procedures
| Table 1 Guidance for dosing during bleeding episodes and surgical procedures | ||
| Degree of bleeding/type of surgery | Required factor VIIIlevel (% or IU / dl) | Dose interval (hours) / duration of treatment (number of days) |
| Bleeding | ||
| Early osteoarthritis, muscle bleeding, or bleeding in the mouth. | 20 – 40 | Repeat the injections every 12 to 24 hours. At least 1 day until the bleeding episode (perceived pain) has stopped or healing has been achieved. |
| More extensive osteoarthritis, muscle bleeding or hematoma. | 30 – 60 | Repeat the injectionsevery 12 to 24 hours for 3-4 days or longer until pain relief is achieved and the acute movement restriction is lifted. |
| Life-threatening bleeding. | 60 – 100 | Repeat the injections every 8 to 24 hours until the critical condition is over. |
| Surgical procedure | ||
| LessIncluding tooth extraction. | 30 – 60 | Every 24 hours for at least 1 day, until healing is achieved. |
| Major | 80 – 100 (pre- and postoperatively) | Repeat the injectionsevery 8 to 24 hours until wound healing occurs, then continue treatment for at least another 7 days to maintain a factor VIIIactivity of 30% –60% (IU / dl). |
Prophylaxis
For long-term prophylaxis, a dose of 40 to 50 IU ADYNOVI per kg body weight twice a week at 3-4 day intervals is recommended. Adjusting the dose you and the administration range can be considered depending on the achievement of FVIII levels and individual bleeding tendency (see section 5.2).
Pediatric population
The dosage one for use, when needed, is the same for pediatric patients (12 to 18 years) as for adult patients. Prophylactic treatment of patients from 12 to <18 years of age is the same as for adult patients. The long-term safety of ADYNOVI in children under 12 years of age has not yet been established. Adjusting the dose you and the administration range can be considered depending on the achievement of FVIII levels and individual bleeding tendency (see section 5.2).