ADVATE 3000 IU powder and solvent for solution for injection

 

What is it and how is it used?

ADVATE contains the active substance octocog alfa, human coagulation factor VIII produced by recombinant DNA technology. Factor VIII is necessary for the blood to form clots and stop bleedings. In patients with haemophilia A (inborn factor VIII deficiency), it is missing or not working properly.

ADVATE is used in patients with haemophilia A for prevention or treatment of spontaneous or surgery-related bleeding.

ADVATE is prepared without the addition of any human- or animal-derived protein in the cell culture process, purification or final formulation.

What do you have to consider before using it?

Do not use ADVATE

  • if you are allergic (hypersensitive) to octocog alfa or any of the other ingredients of ADVATE
  • if you are allergic to mouse or hamster proteins If you are unsure about this, ask your doctor.

Take special care with ADVATE
You should tell your doctor if you have been previously treated with Factor VIII products, especially if you developed inhibitors, since there might be a higher risk that it happens again. Inhibitors are blocking antibodies against factor VIII that reduce the efficacy of ADVATE to prevent or control bleeding. Development of inhibitors is a known complication in the treatment of haemophilia A. If your bleeding is not controlled with ADVATE, tell your doctor immediately.

There is a rare chance that you may experience an anaphylactic reaction (a severe, sudden allergic reaction) to ADVATE. You should be aware of the early signs of allergic reactions such as rash, hives, wheals, generalised itching, swelling of lips and tongue, difficulty in breathing, wheezing, tightness in the chest, general feeling of being unwell, and dizziness. These symptoms can constitute an early

symptom of an anaphylactic shock, manifestations of which may additionally include extreme dizziness, loss of consciousness, and extreme difficulty in breathing.
If any of these symptoms occur, stop the injection immediately and contact your doctor. Severe symptoms, including difficulty in breathing and (near) fainting, require prompt emergency treatment.

Taking other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding
Tell your doctor if you are pregnant or breast-feeding.
Your doctor will decide if ADVATE may be used during pregnancy and breast-feeding.

Driving and using machines
ADVATE has no influence on your ability to drive or to use machines.

Important information about some of the ingredients of ADVATE
This medicinal product contains 0.45 mmol sodium (10 mg) per vial. To be taken into consideration by patients on a controlled sodium diet.

How is it used?

Treatment with ADVATE will be started by a doctor who is experienced in the care of patients with haemophilia A.

Your doctor will calculate your dose of ADVATE (in international units or IU) depending on your condition and body weight, and on whether it is used for prevention or treatment of bleeding. The frequency of administration will depend on how well ADVATE is working for you. Usually, the replacement therapy with ADVATE is a life-long treatment.

Prevention of bleeding
The usual dose of octocog alfa is 20 to 40 IU per kg body weight, administered every 2 to 3 days. However, in some cases, especially in younger patients, more frequent injections or higher doses may be necessary.

Treatment of bleeding
The dose of octocog alfa is calculated depending on you body weight and the factor VIII levels to be achieved. The target factor VIII levels will depend on the severity and location of the bleeding. Dose (IU) = body weight (kg) x desired Factor VIII rise (% of normal) x 0.5

If you have the impression that the effect of ADVATE is insufficient, talk to your doctor. Your doctor will perform appropriate laboratory tests to make sure that you have adequate Factor VIII levels. This is particularly important if you are having major surgery.

Patients developing Factor VIII inhibitors
If your plasma Factor VIII fails to reach expected levels with ADVATE, or if bleeding is not adequately controlled, it could be due to the development of Factor VIII inhibitors. This will be checked by your doctor. You might need a higher dose of ADVATE or even a different product to control bleedings. Do not increase the total dose of ADVATE to control your bleeding without consulting your doctor.

How ADVATE is given
ADVATE is usually injected into a vein (intravenously) by your doctor or nurse. You or someone else might also administer ADVATE as an injection, but only after receiving adequate training. Detailed instructions for self-administration are given at the end of this package leaflet.

If you use more ADVATE than you should
Always take ADVATE exactly as your doctor has told you. You should check with your doctor if you are not sure. If you inject more ADVATE than recommended, tell your doctor as soon as possible.

If you forget to use ADVATE
Do not inject a double dose to make up for a forgotten dose. Proceed with the next injection as scheduled and continue as advised by your doctor.

If you stop using 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.

What are possible side effects?

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

If severe, sudden allergic reactions (anaphylactic) occur, the injection must be stopped immediately. You must contact your doctor immediately if you have any of the following early symptoms of allergic (hypersensitivity) reactions:

  • rash, hives, wheals, generalised itching,
  • swelling of lips and tongue,
  • difficulty in breathing, wheezing, tightness in the chest,
  • general feeling of being unwell,
  • dizziness and loss of consciousness. Severe symptoms, including difficulty in breathing and (nearly) fainting, require prompt emergency treatment.

Side effects may occur with certain frequencies, which are defined as follows:
very common: affects more than 1 user in 10
common: affects 1 to 10 users in 100
uncommon: affects 1 to 10 users in 1,000
rare: affects 1 to 10 users in 10,000
very rare: affects less than 1 user in 10,000
not known: frequency cannot be estimated from the available data.

Common side effects
dizziness, headache and fever.

Uncommon side effects
itching, increased sweating, unusual taste in the mouth, hot flushes, migraines, memory impairment, chills, diarrhoea, nausea, vomiting, shortness of breath, sore throat, infection of the lymphatic vessels, whitening of skin, eye inflammation, rashes, excessive sweating, foot and leg swelling, increase in enzymes that track liver function, reduced percentage of red blood cells and pain in the upper abdomen or lower chest.

Related to surgery
catheter-related infection, decreased red cell blood count, swelling of limbs and joints, prolonged bleeding after drain removal, decreased Factor VIII level and post-operative bruise.

Rare side effects
Since the medicine has been on the market, there have been rare reports of severe and potentially life-threatening reactions (anaphylaxis) and other allergic reactions (see above).

If any of these side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

How should it be stored?

Keep out of the reach and sight of children.

Do not use ADVATE after the expiry date, which is stated on the label after EXP. The expiry date refers to the last day of that month.

Store in a refrigerator (2°C – 8°C). Do not freeze.

During the shelf life the powder vial may be kept at room temperature (up to 25°C) for a single period not exceeding 6 months. Please record the beginning of storage at room temperature on the product carton. The product may not be returned to refrigerated storage after storage at room temperature.

Keep the vial in the outer carton in order to protect from light.

This product is for single use only. Discard any unused solution appropriately.
Use the product immediately once the powder is completely dissolved.
Do not refrigerate the solution after preparation.

Medicines should not be disposed of via waste water or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What is it?

Advate is a powder and solvent that are mixed together to make a solution for injection. Advate contains the active substance octocog alfa (human coagulation factor VIII).

What is it used for?

Advate is used for the treatment and prevention of bleeding in patients with haemophilia A (an inherited bleeding disorder caused by lack of factor VIII). Advate is intended for either short-term or long-term use.
The medicine can only be obtained with a prescription.

How is it used?

Advate should be started by a doctor who has experience in the treatment of haemophilia. Advate is given by injection into a vein at a rate of up to 10 ml per minute. The dose and frequency depend on whether Advate is used to treat haemorrhage (bleeding) or to prevent it during surgery. The dose is also adjusted depending on the severity of the haemorrhage or the type of surgery. Full details on how to calculate the doses are included in the Package Leaflet.

How does it work?

The active substance in Advate, octocog alfa, is a blood coagulation factor protein. In the body, factor VIII is one of the substances (factors) involved in blood coagulation (clotting). Patients with haemophilia A lack factor VIII, and this causes blood coagulation problems, such as bleeding in the joints, muscles or internal organs. Advate is used to replace the missing factor VIII. It corrects the factor VIII deficiency and gives temporary control of the bleeding disorder.
Octocog alfa is not extracted from human plasma but produced by a method known as ‘recombinant DNA technology’: it is made by a cell that has received a gene (DNA), which makes it able to produce human coagulation factor VIII.

How has it been studied?

Advate is similar to another medicine approved in the European Union (EU) called Recombinate, but it is prepared differently so that there are no human- or animal-derived proteins in the medicine. Because of this, the main study done with Advate compared it with Recombinate in 111 patients with haemophilia A to show that the two medicines are equivalent. The study went on to look at the number of bleeding episodes and rated Advate’s effectiveness in stopping bleeding on a scale from ‘none’ to ‘excellent’ in 107 patients, all of whom received Advate.
Three additional studies looked at the use of the medicine in the prevention of bleeding and in surgery in patients with severe or moderately severe haemophilia A, including one study in 53 children under the age of six years.

What benefits has it shown during the studies?

In the main study, the effectiveness of Advate in the prevention of bleeding was rated as ‘excellent’ or ‘good’ in 86% of the 510 new bleeding episodes. In addition, 81% of these bleeding episodes required only a single treatment with Advate.
The additional studies confirmed Advate’s effectiveness, including in children under six years of age.

What is the risk associated?

Haemophilia A patients may develop antibodies (inhibitors) to factor VIII. An antibody is a protein produced by the body in reaction to unknown agents as part of the natural defence system of the body. If antibodies develop, Advate will not work effectively. The most common side effects with Advate (seen in between 1 to 10 patients in 100) are dizziness, headache, pyrexia (fever) and the presence of antibodies against factor VIII. Hypersensitivity (allergic reactions) has sometimes been seen in patients treated with factor VIII-containing products. For the full list of all side effects reported with Advate, see the Package Leaflet.
Advate should not be used in people who may be hypersensitive (allergic) to human coagulation factor VIII, to mouse or hamster protein, or to any of the other ingredients.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Advate’s benefits are greater than its risks for the treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). The Committee recommended that Advate be given marketing authorisation.

Further information

The European Commission granted a marketing authorisation valid throughout the EU for Advate to Baxter AG on 2 March 2004. The marketing authorisation was renewed on 2 March 2009.