250 IU, 500 IU, 1000 IU, 1500 IU powder and solvent for solution for injection.
Octocog alfa ( recombinant human coagulation factor VIII)
1. What ADVATE is and what it is used for
ADVATE contains the active substance octocog alfa, human coagulation factor VIII produced by recombinant DNA technology. Factor VIII is needed for the blood to form clots and stop bleeding. In patients with hemophilia A (congenital factor VIIIdeficiency ), this is absent or does not function normally.
ADVATE is used to treat and prevent bleeding in patients of all ages who have hemophilia A (a hereditary form of hemophilia caused by a factor VIII deficiency ).
ADVATE is manufactured without the addition of any human or animal protein throughout the manufacturing process.
2. What you need to know before using ADVATE
Do not use ADVATE
- If you are allergic to octocog alfa or any of the other ingredients of this medicine (listed in section 6).
- If you are allergic to mouse or hamster protein.
If you are not sure, ask your doctor.
Warnings and cautions
Talk to your doctor before using ADVATE. Tell your doctor if you have previously been treated with factor VIII products, especially if you have developed inhibitors, as there may be a greater risk of recurrence. Inhibitors are blocking antibodies to factor VIII, which reduce the effect of ADVATE in preventing or controlling bleeding. The development of inhibitors is a known complication in the treatment of hemophilia. Contact your doctor immediately if your bleeding is not controlled with ADVATE.
There is a small risk of you getting an anaphylactic reaction (a severe, sudden allergic reaction ) from ADVATE. You should be aware of early signs of allergic reactions such as rash, hives, general itching, swelling of the lips and tongue, difficulty breathing, pressure over the chest, general malaise, and dizziness. These symptoms can be an early symptom of anaphylactic shock, reactions that may also include severe dizziness, unconsciousness, and severe difficulty breathing.
If you experience any of these symptoms, stop the injection/infusion immediately, and contact your doctor. Severe symptoms, such as difficulty breathing and fainting, require immediate emergency treatment.
Patients developing factor VIII inhibitors
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 suffer from bleeding that cannot be controlled with ADVATE, tell your doctor immediately.
Children and young people
The information on warnings and precautions applies to both adults and children (from 0 to 18 years).
Other medicines and ADVATE
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.
Driving and using machines
ADVATE has no effect on the ability to drive and use machines.
ADVATE contains sodium
This medicine contains 0.45 mmol sodium (10 mg) per vial. This should be considered by patients on a low-salt diet.
Incorrect administration of ADVATE
Improper administration ( injection into an artery or outside the vein) should be avoided, as mild, short-term reactions at the injection site, such as bruising and erythema, may occur.
3. How to use ADVATE
Treatment with ADVATE will be initiated by a physician experienced in the management of patients with hemophilia A.
Your doctor will calculate the dose of an ADVATE (in international units or IU) 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 ADVATE works on you. Replacement treatment with ADVATE is usually a lifelong treatment.
Always use this medicine exactly as your doctor has told you. Consult a doctor if you are unsure.
Prevention of bleeding
The usual dose is 20 – 40 IU octocog alfa per kg body weight given every two to three days. In some cases, especially in young patients, more frequent injections or higher doses may be necessary.
Treatment of bleeding
The dose of octocog alfa is calculated depending on your body weight and the factor VIII levels to be achieved. The desired factor VIII level depends on the location and severity of the bleeding.
| Dose (IU) = body weight (kg) x desired factor VIII increase (% of normal) x 0.5 |
If you have the impression that ADVATE is not working properly, talk to your doctor.
Your doctor will perform appropriate laboratory tests to ensure that you have adequate factor VIII levels. This is especially important if you are having major surgery.
Use in children and adolescents (from 0 to 18 years)
When it comes to treating bleeding, the dose for children is the same as for adult patients. When it comes to preventing bleeding in children under 6 years of age, a dose of 20 to 50 IU per kg body weight is recommended 3 to 4 times a week. Administration of ADVATE to children ( intravenously ) does not differ from administration to adults. A central venous access device may be required to enable frequent infusion of factor VIII products.
Due to the reduced injection volume of ADVATE reconstituted in 2 ml, there is even less time to react to hypersensitivity reactions. Therefore, caution is recommended when injecting ADVATE reconstituted in 2 ml, especially for children.
How ADVATE is given
ADVATE is usually injected into a vein ( intravenously ) by your doctor or nurse. You or someone else can also give ADVATE 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 ADVATE than you should
Always take ADVATE exactly as your doctor has told you. Consult a doctor if you are unsure. If you inject more ADVATE than recommended, tell your doctor as soon as possible.
If you forget to take ADVATE
Do not inject 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 taking ADVATE
Do not stop using ADVATE 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.
If severe, sudden allergic (anaphylactic) reactions occur, discontinue injection immediately. You must contact your doctor immediately if you get any of the following early signs of allergic reactions:
- rash, hives, general itching,
- swelling of the lips and tongue,
- difficulty breathing, wheezing, pressure over the chest,
- general malaise,
- dizziness, unconsciousness.
Severe symptoms, such as difficulty breathing and fainting, require immediate emergency treatment.
In children who have not been previously treated with factor VIII drugs, it is very common for inhibitory antibodies to develop (see section 2) (affects more than 1 user in 10). However, for patients who have previously been treated with factor VIII(treatment for more than 150 days), the risk is less and the complication is less common (occurs in less than 1 in 100 users). If you or your child develop antibodies, the medicines may stop working properly and you or your child may suffer from persistent bleeding. If this happens, consult a doctor immediately.
A very common side effect is (occurring in more than 1 in 10)
Factors VIII inhibitors (in children not previously treated with factor VIII medicines).
Common adverse s (affects up to 1 in 10)
Headache and fever.
Less common side effects are (affects up to 1 in 100)
Inhibitors of factor VIII (in patients who have been treated with factor VIII -previously (treatment for more than 150 days)), dizziness, influenza, fainting, abnormal heart rhythm, red itchy lumps on the skin, chest discomfort, bruising at the injection site, reaction to the injection site, itching, increased sweating, unusual taste in the mouth, swelling, migraine, memory problems, chills, diarrhea, nausea, vomiting, shortness of breath, sore throat, infection of the lymph vessels, pallor, eye inflammation, eczema, profuse sweating, swollen legs, feet decreased proportion of red blood cells in the blood, increased number of a certain type of white blood cells ( monocytes ) and pain in the upper abdomen or lower chest.
In connection with surgery
catheter-related infection, decreased red blood cell count, swelling of extremities joints, prolonged bleeding after drainage removal, decreased factor VIII level, and postoperative bruising.
In connection with the device for central venous access
Catheter-related infection, systemic infection, and local blood clot at the catheter site.
Adverse reactions with an unknown frequency (cannot be calculated from the available data).
Potentially life-threatening reactions ( anaphylaxis ) and other allergic reactions (hypersensitivity), general symptoms (fatigue, weakness).
Additional side effects are in children
In addition to the development of inhibitors in pediatric patients not previously treated, as well as catheter-related complications, no age-specific differences in adverse reactions were observed during clinical trials.
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 ADVATE
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 after EXP. The expiration date is the last day of the specified month.
Store in a refrigerator (2 ° C – 8 ° C). Do not freeze.
During the shelf life, the powder vial can be stored at room temperature (at a maximum of 25 ° C) for up to 6 months. The expiry date for the medicine is then the end of this 6-month period or the expiry date which is printed on the bottle, whichever is the earlier. Note the end date of the 6-month period on the outer carton. Once the medicine has been stored at room temperature, it must not be put back in the refrigerator.
Keep the vial in the outer carton. Sensitive to light.
This product is for single use only. Dispose of the unused product appropriately.
Use the product immediately when the powder is completely dissolved.
Do not store the product in the refrigerator after preparation.
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 octocog alfa ( human coagulation factor VIII produced by recombinant DNA technology). Each vial of powder nominally contains 250, 500, 1000, or 1500 IU octocog alfa.
- The other ingredients are mannitol, sodium chloride, histidine, trehalose, calcium chloride, trometamol, polysorbate 80, and glutathione (reduced).
Vial with liquid: 2 ml sterile water for injections
What the medicine looks like and the contents of the pack
ADVATE is a white to off-white powder. After reconstitution, the solution is clear, colorless, and free of foreign particles. Each pack also contains a preparation aid (BAXJECT II).
Marketing Authorization Holder and Manufacturer
Marketing Authorisation Holder
Takeda Manufacturing Austria AG
Industriestrasse 67
A ‑ 1221 Vienna
Tel: +800 66838470
Email: medinfoEMEA@shire.com
Manufacturer
Baxalta Belgium Manufacturing SA
Boulevard René Branquart 80
B ‑ 7860 Lessines
Belgium
This leaflet was last modified on 04/2020
Other sources of information
Further information on this medicine is available on the European Medicines Agency web site:
Instructions for preparation and administration
Aseptic technique is necessary during the preparation of the solution and during administration.
Use only the sterile water for injections and the reconstitution aid provided with each package ADVATE. ADVATE must not be mixed with other medicines or solutions.
It is strongly recommended to note the name and batch number of the product each time ADVATE is administered to a patient.
Instructions for preparation
- Do not use this medicine after the expiry date which is stated on the label and carton.
- Do not use BAXJECT II if sterile protection or packaging is damaged or shows any signs of injury. This is indicated by the symbol:
- The solution must not be placed in the refrigerator after preparation.
- If the product is still stored in a refrigerator: remove both ADVATE powder and liquid vials from the refrigerator and allow them to reach room temperature (between 15 ° C and 25 ° C).
- Wash your hands thoroughly with soap and warm water
- Remove the caps from the powder and liquid vials.
- Clean the plugs with injection dryers. Place the bottles on a flat, clean surface.
- Open the packaging of the BAXJECT II by pulling off the paper cover without touching the inside (Fig. A). Do not remove BAXJECT II from its packaging. Do not use BAXJECT II if sterile protection or packaging is damaged or shows any signs of injury.
- Turn the package over and push the transparent plastic tip through the rubber stopper of the water bottle. Grasp the edges of the package and pull the package away from the BAXJECT II (Fig. B). Do not remove the blue cap from the BAXJECT II.
- Only sterilized water for injections and the reconstitution aid provided in the package should be used for reconstitution. Turn the entire system with BAXJECT II attached to the water bottle so that the water bottle ends up on top. Push the white plastic tip through the rubber stopper of the ADVATE powder bottle. The water will be sucked into the ADVATE powder bottle by vacuum (Fig. C).
- Carefully rotate the bottle until all the powder is dissolved. Make sure that the ADVATE powder is completely dissolved, otherwise not all the reconstituted solution can pass through the filter. The product dissolves quickly (usually in less than 1 minute). After reconstitution, the solution should be clear, colorless, and free of foreign particles.
Instructions for injection
For administration, a syringe with a Luer cap is required.
Important information:
- Do not try to inject the solution yourself unless you have been trained by your doctor or nurse to do so.
- Inspect the reconstituted solution for particulate matter and discoloration prior to administration (the solution should be clear, colorless, and free of foreign particles).
Do not use ADVATE if the solution is not completely clear or not completely dissolved.
- Remove the blue cap from the BAXJECT II. Do not draw air into the syringe. Connect the syringe to BAXJECT II (Fig. D).
- Turn the system over (so that the bottle of the reconstituted solution is on top). Pull the reconstituted solution into the syringe by slowly pulling out the plunger (Fig. E).
- Remove the syringe.
- Connect a “butterfly” needle to the syringe and inject the reconstituted solution into a vein. The solution should be administered slowly, at a rate determined according to the patient’s condition, and should not exceed 10 ml per minute. (See section 4 “Possible side effects”.)
- Dispose of the unused product appropriately.
The following information is intended for medical professionals only:
Treatment if necessary
In the event of the following hemorrhagic events, the factor VIII activity should not be less than the given plasma activity level (in% of normal or IU / dl) during the corresponding period. The following table can be used as a dosing guide for bleeding episodes and surgeries.
The dose and interval of administration should be adjusted according to the clinical effect of the individual case. In special circumstances (eg in the presence of a low titer inhibitor) higher doses than those calculated according to the formula may be required.
| Degree of bleeding / type of surgery | Required factor VIIIlevel (% or IU / dl) | Dose interval (hours) / duration of treatment (days) |
| Bleeding Early home osteoarthritis, muscle bleeding, or mouth bleeding. | 20 – 40 | Repeat injection once every 12-24 hours (8-24 hours for patients younger than 6 years) for at least 1 day until the bleeding episode (pain experienced) has ceased or healing has been achieved. |
| More extensive osteoarthritis, muscle bleeding or hematoma. | 30 – 60 | Repeat injection once every 12-24 hours (8-24 hours for patients younger than 6 years) for 3-4 days or longer until pain relief and acute movement restriction are lifted. |
| Life-threatening bleeding. | 60 – 100 | Repeat injection once every 8-24 hours (6-12 hours for patients younger than 6 years) until the critical condition is overcome. |
| Surgery LessIncluding tooth extraction. | 30 – 60 | Every 24 hours (12-24 hours for patients younger than 6 years) for at least 1 day, until healing is achieved. |
| Major | 80 – 100(pre- and postoperatively) | Repeat injection once every 8-24 hours (6-24 hours for patients younger than 6 years) until wound healing occurs, then continue treatment for at least another 7 days to maintain a factor VIIIactivity of 30-60% (IU / dl) |