What is in this leaflet
Read this leaflet carefully before you start using ADVATE. This leaflet answers some common questions about ADVATE.
It does not contain all of the available information.
It does not take the place of talking to your doctor or pharmacist.
All medicines have risks and benefits. Your doctor has weighed the risks of you using ADVATE against the benefits they expect it will have for you.
If you have any concerns about taking this medicine ask your doctor or pharmacist.
Keep this leaflet. You may wish to read it again.
Information in this leaflet is subject to change over time.
Ask your doctor or visit the Health Authority website (in Australia: www.ebs.tga.gov.au; in New Zealand: www.medsafe.govt.nz) for the latest Consumer Medicine Information.
What is ADVATE used for
ADVATE belongs to the group of medicines called blood coagulation factor VIII.
It is used for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency).
ADVATE does not contain von Willebrand factor and is therefore not suitable for use in von Willebrand's disease.
ADVATE contains the active ingredient octocog alfa, which is a human recombinant coagulation factor VIII produced by recombinant DNA technology.
How does ADVATE work
Under normal physiological condition, factor VIII is essential for blood clotting and maintenance of a bleeding episode.
Individuals with haemophilia A disease, which is a hereditary disorder of blood coagulation have a low level of factor VIII in their blood circulation. As a result of factor VIII deficiency, the individual with this disease may have a heavy bleeding into joints, muscles or internal organs either spontaneously or as a result of accidental or surgical trauma.
ADVATE is similar to and works in the same way as plasma-derived factor VIII. As such, it can be used as a replacement therapy to correct the factor VIII deficiency in patients with haemophilia A.
Before you are given the ADVATE
ADVATE should not be given to you if:
- you are allergic (hypersensitive) to mouse, hamster proteins or any other ingredients in this product;
- you have tendency of allergic reaction or hypersensitivity to any human derived injection. Some of the symptoms of allergic reaction may include skin rash, swelling of the face, lips or tongue, which may cause difficulty swallowing or shortness of breath, tightness of the chest;
- the expiry date printed on the pack has passed;
- the packaging is torn or shows sign of tampering;
- the pack has been stored at room temperature for more than 6 months;
- the injection solution has been prepared for more than 3 hours.
You must tell your doctor if you:
- have any other illness.
Tell your doctor if you are pregnant or breast feeding, or planning to become pregnant or breast feed. There is no information on the use of ADVATE during pregnancy.
It is not known whether ADVATE passes into breast milk.
Your doctor will discuss the risks and benefits of using ADVATE if you are pregnant or breast feeding or if you have any plans to do so.
Taking other medicines
Tell your doctor or pharmacist or Haemophilia Treatment Centre if you are using any other medicines including any that you obtained without a prescription from your pharmacy, supermarket or health food shop.
No drug interactions have been reported with ADVATE, but your doctor or pharmacist or Haemophilia Treatment Centre will have more information on medicines to be careful with or avoid while using this medicine.
How ADVATE is given
Treatment with ADVATE should be given under the supervision of a specialist doctor experienced in the treatment of haemophilia A.
Follow all directions given to you by your doctor carefully. They may differ from the information contained in this leaflet.
Each time you use ADVATE, keep a record of the name and batch number of the medicine.
How much is given
Your doctor will decide how much ADVATE will be given to you depending on your need and condition. Each individual will receive a different dosage, which may vary between doctor visits.
The dose you receive will be based on:
- your body weight;
- the amount of antihaemophilic factor (AHF) your body is able to make;
- how much and how often and which sites (knees, muscles etc.) of your body are bleeding;
- whether your body may build up antibodies to this medicine. After a while your body may build up these antibodies, leading to a less effective treatment than the usual.
How it is given
ADVATE is given by a slow injection directly - into your vein.
ADVATE is usually administered in a hospital. Some individuals may be trained to use ADVATE at home.
Do not attempt to inject ADVATE by yourself unless you have received proper training on how to use the product by your doctor or other healthcare professional, e.g. a haemophilia nurse.
If you are unsure about how to use this medicine, contact your doctor or healthcare professional for advice.
Method of administration (use aseptic technique)
Aseptic (meaning clean and germ free) technique is required for the handling, preparing and administration of ADVATE.
Before the injection is given, ADVATE needs to be prepared into a solution for injection by mixing the powder with water for injections.
Detailed instructions for the preparation and administration of ADVATE are given at the end of this leaflet.
Follow carefully the instructions for use given at the end of this leaflet for preparing the solution for injection, and for injecting ADVATE.
Ask your doctor or Haemophilia Treatment Centre for help if you do not understand the instructions given in this leaflet.
Use only the reconstitution device provided with each pack to prepare the solution for injection.
Do not mix ADVATE with any other medicines or solvent other than the water for injections supplied with the pack.
After preparing the solution, use the solution straight away or within 3 hours.
Do not refrigerate the solution after it is prepared.
Before injection, check the solution to make sure it is clear, colourless and free of any visible particles.
Do not use the solution if it contains visible particles or looks cloudy.
Use a new syringe and needle for each injection.
How often is it given
Your doctor will tell you how often and what intervals ADVATE is to be administered.
If you miss / forget your injection
Do not inject a double dose to make up for the forgotten dose. If you inject a double dose, it will increase the chance of you getting an unwanted side effect.
Contact your doctor or Haemophilia Treatment Centre for advice and give the next injection as advised by your doctor.
If you use too much (overdose)
No symptoms of overdose with ADVATE have been reported.
Immediately telephone your doctor or the National Poisons Information Centre (in Australia: telephone 131 126; in New Zealand: telephone 0800 POISON or 0800 764 766) for advice, or go to accident and emergency at your nearest hospital, if you think that you or anyone else may have been given too much ADVATE.
Do this even if there are no signs of discomfort or poisoning.
You may need urgent medical attention.
While you are using ADVATE
Things you must do
Continue using your medicine for as long as your doctor tells you.
This medicine helps to control your condition, but does not cure it.
Attend all your doctor's appointments so that your progress can be checked.
Discuss with your doctor the progress you have experienced after the treatment, especially during the first few days. Your healthcare professional will take records of the progress and unexpected reactions.
You will have your blood tested before you start your treatment and regularly from time to time during your treatment to see how your treatment is working.
Monitor your bleeding and tell your doctor immediately if your bleeding is not controlled after using ADVATE.
While you are receiving the injection, tell your doctor or nurse immediately if you feel unwell. If you are giving the injection by yourself, stop the injection immediately if you feel unwell.
Allergic reaction may occur during an injection and if this occurs, you may need immediate medical attention.
If you are planning for any surgery or dental procedures, tell your doctor and dentist that you are using ADVATE.
Things you must not do
Do not give ADVATE to anyone else even if they appear to have the same condition as you.
Do not stop using ADVATE or change the dose without checking with your doctor.
Side Effects
Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using ADVATE.
All medicines can have side effects. Sometimes they are serious, most of the time they are not.
You may need medical attention if you get some of these side effects.
Do not be alarmed by this list of possible side effects, you may not experience any of them.
Ask your doctor or pharmacist to answer any questions you may have.
Tell your doctor immediately if your bleeding is not being controlled by ADVATE as expected. Inhibitor antibodies against the medicine may form during the course of treatment. If this happens, ADVATE may stop working properly. This is a very common side effect in patients who have not been previously treated with factor VIII medicines. In patients who have received previous treatment with factor VIII (for more than 150 days), the risk of developing inhibitor antibodies is uncommon.
Tell your doctor, nurse or pharmacist if you notice any of the following and they worry you:
- headache;
- fever.
The above list includes the common side effects of ADVATE.
- flu;
- sore throat;
- infection of the lymphatic vessels;
- dizziness;
- unusual taste in the mouth;
- memory impairment;
- migraines;
- fainting;
- tremor
- eye inflammation;
- fast or irregular heartbeats;
- bruise;
- hot flushes;
- looking pale;
- shortness of breath;
- pain in upper abdomen;
- diarrhoea;
- nausea;
- vomiting;
- increased or excessive sweating;
- itching, rash or hives;
- discomfort or pain in the chest;
- chills;
- feeling abnormal;
- swelling of hands, ankles or feet;
- injection site reactions;
- bleeding or bruising around the injection site;
- increased, decreased or abnormal level of certain blood test results.
The above list includes the uncommon side effects of ADVATE.
If any of the following happen suddenly, tell your doctor immediately or go to Emergency at the nearest hospital:
- rash, hives, wheals, generalised itching;
- swelling of your face, lips and tongue or any parts of the body;
- shortness of breath, difficulty in breathing, wheezing, tightness in the chest,
- general feeling of being unwell,
- dizziness and loss of consciousness.
The above list includes serious side effects which are early symptoms of an allergic response to the medicine, which in some cases could progress to anaphylaxis (including shock) and require urgent medical attention or hospitalisation.
Allergic reactions (hypersensitivity) have been reported in patients with an unknown frequency. If any of the above symptoms of allergic reaction occur during the ADVATE injection, stop the injection immediately.
Tell your doctor or Haemophilia Treatment Centre if you notice anything that is making you feel unwell.
After using ADVATE
Storage
All medicines should be kept where children cannot reach them.
Store ADVATE in the refrigerator at 2°C to 8°C.
Do not freeze ADVATE.
Keep ADVATE in the pack until it is time to use it. The packaging will protect the medicine from light.
Unopened vials stored in the pack can be kept in the refrigerator at 2°C to 8°C until its expiry date which is printed on the packaging.
If necessary, ADVATE can be kept in the sealed carton out of the refrigerator for a single period of up to 6 months when stored in a cool dry place where the temperature stays below 25°C.
Once ADVATE has been kept out of the refrigerator and stored at room temperature (below 25°C), do not return the product back to the refrigerator and use the product within 6 months. The medicine expires 6 months after the pack is stored at room temperature, or after the expiry date has passed, whichever is earlier.
Once the solution is prepared (after mixing the powder with the water for injections), use the solution straight away or within 3 hours.
Do not refrigerate the solution after it is prepared.
Disposal
Discard any solution left in the vial at the end of your injection. ADVATE is for single use in single patient only. It does not contain antimicrobial preservative.
Dispose the used vials and all materials in an appropriate container.
If your doctor tells you to stop using ADVATE or the expiry date has passed, ask your Haemophilia Treatment Centre what to do with any medicine that is left over.
Ask your doctor or Haemophilia Treatment Centre if you have any questions about how to dispose ADVATE.
Product descriptions
What ADVATE looks like
ADVATE is a white to cream colour powder in a single dose glass vial. After reconstitution, the solution is clear, colourless and free from foreign particles.
Each pack of ADVATE contains:
- 1 vial of ADVATE powder for injection;
- 1 vial of water for injections (which is a diluent to dissolve the powder for injection);
- 1 reconstitution device.
ADVATE is available in the following strengths, which may be supplied with either a 5 mL or 2 mL vial of water for injections:
- 250 IU (5 mL or 2 mL);
- 500 IU (5 mL or 2 mL);
- 1000 IU (5 mL or 2 mL);
- 1500 IU (5 mL or 2 mL);
- 2000 IU (5 mL);
- 3000 IU (5 mL);
- 4000 IU (5 mL).
No all presentations are marketed.
The 5 mL water for injections vial has a grey cap and the 2 mL water for injections vial has a clear colourless cap.
Ingredients
Active ingredient:
- octocog alfa [also known as antihaemophilic factor VIII; recombinant coagulation factor VIII (rhc)]
Inactive ingredients:
- trehalose dihydrate;
- histidine;
- mannitol;
- polysorbate 80;
- sodium chloride;
- calcium chloride dihydrate;
- glutathione;
- trometamol;
- water for injections (diluent).
Sponsor
ADVATE is supplied in Australia by:
Takeda Pharmaceuticals Australia Pty Ltd
Level 39, 225 George Street
Sydney NSW 2000
Australia
Telephone: 1800 012 612
www.takeda.com/en-au
ADVATE is supplied in New Zealand by:
Takeda New Zealand Limited
Level 10, 21 Queen Street
Auckland 1010
New Zealand
Telephone: 0508 169 077
www.takeda.com/en-au
Australian registration numbers
AUST R 100384
(ADVATE 250 IU)
AUST R 100385
(ADVATE 500 IU)
AUST R 100386
(ADVATE 1000 IU)
AUST R 100387
(ADVATE 1500 IU)
AUST R 136204
(ADVATE 2000 IU)
AUST R 150366
(ADVATE 3000 IU)
AUST R 214709
(ADVATE 4000 IU)
Date of preparation
This leaflet was prepared in October 2020.
Instructions for use
For intravenous use only
IMPORTANT:
Contact your doctor or local Haemophilia Treatment Centre if you have any questions or if you experience any problems with this procedure.
These instructions are intended only as a visual aid for those patients who have been instructed by their doctor or Haemophilia Treatment Centre on the proper way to self-inject the product.
Do not attempt to inject ADVATE by yourself unless you have been trained by your doctor or Haemophilia Treatment Centre.
Use only the water for injections and the BAXJECT II reconstitution device provided in the pack to prepare the solution for injection. If more than one vial of ADVATE is needed for the dose, reconstitute each vial of ADVATE using a separate BAXJECT II reconstitution device supplied in each pack.
Do not refrigerate the solution after reconstitution.
Use the reconstituted solution as soon as possible, within 3 hours after reconstitution.
Before administering the dose, visually inspect the reconstituted solution. The solution should appear clear and colourless.
Do not use the solution if there is any visible particulate matter or discolouration.
Use aseptic technique
In a quiet place, prepare a clean surface and gather all the materials you will need for the injection.
Remove ADVATE from the refrigerator and check the expiry date on the package.
Wash your hands and put on clean exam gloves. If you are self-injecting at home, the use of gloves is optional.
Using the BAXJECT II device
- Allow the ADVATE (factor concentrate powder) and the diluent vials to reach room temperature before use.
- Remove plastic caps from the ADVATE and diluent vials.
- Cleanse rubber stoppers with an alcohol wipe and allow the stoppers to dry before use.
- Open the BAXJECT II device package by peeling away the lid, without touching the inside (Figure A). Do not remove the device from the package.
Figure A
- Turn the package over. Press straight down to fully insert the clear plastic spike though the diluent vial stopper (Figure B).
Figure B
- Grip the BAXJECT II package at its edge and pull the package off the device (Figure C). Do not remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike.
Figure C
- Turn the system over so that the diluent vial is on top. Quickly insert the white plastic spike fully into the ADVATE vial stopper by pushing straight down (Figure D). The vacuum will draw the diluent into the ADVATE vial.
Figure D
- Swirl gently until ADVATE is completely dissolved. DO NOT SHAKE.
Administration
- Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device (Figure E). DO NOT INJECT AIR into the BAXJECT II device.
Figure E
- Turn the system upside down (ADVATE vial now on top). Draw the reconstituted solution into the syringe by pulling the plunder back slowly (Figure F).
Figure F
- Disconnect the syringe, attach a suitable needle and inject slowly into the vein over a period of up to 5 minutes (maximum infusion rate of 10 mL per minute).
- If more than one vial of ADVATE is to be used, the contents of multiple vials may be drawn into the same syringe.
ADVATE® and BAXJECT® are registered trademarks of Baxalta Incorporated.
TAKEDA® and the TAKEDA Logo® are registered trademarks of Takeda Pharmaceutical Company Limited.
Published by MIMS December 2020
In case of the haemorrhagic events as shown in Table 1, the factor VIII activity should not fall below the given plasma activity level (in % normal or IU/dL) in the corresponding period. Table 2 can be used to guide dosing in bleeding episodes and surgery.
In a post-hoc analysis, the overall rate of bleeding was correlated with the degree of compliance with the prescribed prophylactic regimen. Subjects who infused less than 25 IU Advate per kg per dose for more than 20% of prophylactic infusions or administered less than 3 infusions per week for more than 20% of study weeks (n = 37) experienced a 2.3-fold higher rate of bleeding in comparison with subjects who complied with prescribed prophylactic regimen at least 80% of the time and at ≥ 80% of the prescribed dose (n = 70).
The annualised bleed rates by age category during on-demand and either standard or PK-guided prophylaxis regimens are shown in Table 7.
As a secondary endpoint, the study assessed all Short Form Health Survey (SF-36v1) domains. The SF-36v1 is a valid and reliable measure of health-related quality of life that is comprised of 8 domain and 2 summary scores (Table 8).
