drug-medicine : avastin

PACKAGE LEAFLET: INFORMATION FOR THE USER

Avastin 25 mg/ml concentrate for solution for infusion

Bevacizumab

Read all of this leaflet carefully before you start using this medicine.

Keep this leaflet. You may need to read it again.
If you have any further questions, ask your doctor or pharmacist.
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell you doctor or pharmacist.

In this leaflet:

1. What Avastin is and what it is used for
2. Before you use Avastin
3. How to use Avastin
4. Possible side effects
5. How to store Avastin
6. Further information

1. WHAT AVASTIN IS AND WHAT IT IS USED FOR

Avastin is used for the treatment of advanced cancer in the large bowel, i.e., in the colon or rectum.

This medicine will be administered with chemotherapy, containing medicines called 5-fluorouracil and folinic acid. A medicine called irinotecan might also be part of the chemotherapy.

Avastin is also used for the treatment of metastatic breast cancer. When used for patients with breast cancer, it will be administered with a chemotherapy called paclitaxel.

Avastin contains the active substance bevacizumab, which is a humanised monoclonal antibody.

Monoclonal antibodies are proteins which specifically recognise and bind to other unique proteins in the body. Bevacizumab binds selectively to a protein called human vascular endothelial growth factor (VEGF), which is found on the lining of blood and lymph vessels in the body. VEGF causes blood vessels to grow within tumours, these blood vessels provide the tumour with nutrients and oxygen.

Once bevacizumab is bound to VEGF, it stops VEGF working properly. This has the effect of preventing tumour growth by blocking the growth of the blood vessels providing the nutrients and oxygen to the tumour.

Each pack of Avastin concentrate for solution for infusion contains one vial. This vial contains either 4 ml or 16 ml of a slightly opaque, colourless to pale brown sterile liquid concentrate. The concentrate must be diluted before use to make a solution for intravenous infusion.

2. BEFORE YOU USE AVASTIN

Do not use Avastin if:

you are allergic (hypersensitive) to bevacizumab or to any of the other ingredients of Avastin.
you are allergic (hypersensitive) to Chinese hamster ovary (CHO) cell products or to other recombinant human or humanised antibodies.
you have cancer in your brain which has not been treated.
you are pregnant.

Take special care with Avastin:

if you have conditions causing inflammation inside the abdomen (e.g. diverticulitis, stomach ulcers, colitis associated with chemotherapy), as it is possible that Avastin may increase the risk of developing holes in the gut wall.
if you are going to have an operation, if you have had major surgery within the last 28 days or if you still have an unhealed wound following surgery, you should not receive this medicine as Avastin can increase the risk of bleeding or increase the risk of problems with wound healing after surgery.
if you have high blood pressure which is not well controlled with blood pressure medicines as Avastin can increase the incidence of high blood pressure.
if you have high blood pressure, as you may have a higher risk of having protein in your urine.
if you are over 65 years old and also have had blood clots in your arteries (a type of blood vessel) in the past, as these factors can increase the risk of further blood clots in the arteries.
if you or your family tend to suffer from bleeding problems or you are taking medicines to thin the blood for the treatment of blood clots.
if you have been coughing or spitting blood or had any bleeding in your lungs.
if you have ever received anthracyclines (for example doxorubicin, a specific type of chemotherapy used to treat some cancers) or had radiotherapy to your chest, as Avastin can increase the risk of developing a weak heart.

Please consult your doctor, even if these statements were applicable to you at any time in the past.

Using other medicines

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

If you are also taking irinotecan, another chemotherapy agent which may be used for the treatment of advanced cancer of the large bowel, your doctor may change the dose of irinotecan that you are given if you suffer from severe diarrhoea or a severe reduction in the number of white cells in your blood.

Pregnancy and breast feeding

You must not use this medicine if you are pregnant. Avastin may cause damage to your unborn baby as it may stop the formation of new blood vessels. Your doctor should advise you about using contraception during treatment with Avastin and for at least 6 months after the last dose of Avastin.

Tell your doctor straightaway if you are pregnant, become pregnant during treatment with this medicine, or plan to become pregnant in the near future.

You must not breast-feed your baby during treatment with Avastin and for at least 6 months after the last dose of Avastin, as this medicine may interfere with the growth and development of your baby.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines:

Avastin has not been shown to impair your ability to drive or to use any tools or machines.

3. HOW TO USE AVASTIN

Dosage and frequency of administration

The dose of Avastin needed depends on your body weight and the kind of cancer to be treated. The recommended dose is 5, 10 or 15 mg per kilogram of your body weight. Your doctor will prescribe a dose of Avastin that is right for you. You will be treated with Avastin once every 2 or 3 weeks. The number of infusions that you receive will depend on how you are responding to treatment; you should continue to receive this medicine until Avastin fails to stop your tumour growing. Your doctor will discuss this with you.

Method and route of administration

Avastin is a concentrate for solution for infusion. Depending on the dose prescribed for you, some or all of the contents of the Avastin vial will be diluted with saline solution before use. A doctor or nurse will give you this diluted Avastin solution by intravenous infusion. The first infusion will be given to you over 90 minutes following the administration of your chemotherapy medicines. If this is well-tolerated the second infusion may be given over 60 minutes. Later infusions may be given to you over 30 minutes. After the first dose, Avastin can be administered before or after your chemotherapy medicines.

Whilst you receive this medicine:

The administration of Avastin should be temporarily discontinued:

if you develop severe high blood pressure requiring treatment with blood pressure medicines,
if you have problems with wound healing following surgery,
if you undergo surgery.

The administration of Avastin should be permanently discontinued if you develop:

severe high blood pressure which cannot be controlled by blood pressure medicines; or a sudden severe rise in blood pressure,
presence of protein in your urine accompanied by swelling of your body,
a hole in your gut wall,
a blood clot in your arteries,
any severe bleeding.

If too much Avastin is given:

you may develop a severe migraine. If this happens you should talk to your doctor or pharmacist immediately.

If a dose of Avastin is missed:

your doctor will decide when you should be given your next dose of Avastin. You should discuss this with your doctor.

If you stop treatment with Avastin:

Stopping your treatment with Avastin may stop the effect on tumour growth. Do not stop treatment with Avastin unless you have discussed this with your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

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

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

The side effects listed below were seen when Avastin was given together with chemotherapy. This does not necessarily mean that these side effects were strictly caused by Avastin.

Side effects described as very common were experienced in more than 1 in 10 patients.

Side effects described as common were experienced by up to 1 in 10 patients.

The common (up to 1 in 10 patients) most serious side effects are:

perforation of the gut,
bleeding, including bleeding in the lungs in patients with non-small cell lung cancer,
blocking of the arteries by a blood clot.

The severe side effects, which may be very common (more than 1 in 10 patients), include:

high blood pressure,
problems with wound healing after surgery,
feeling of numbness or tingling in hands or feet.
decreased number of white cells in the blood that help to fight against infections,
lack of energy or tiredness.

The severe side effects which may be common (up to 1 in 10 patients), include:

decreased number of cells in the blood, these include white cells (which may occur with a fever), red cells and cells that help the blood to clot,
bleeding associated with the tumour,
lack of energy,
abdominal pain,
dry mouth in combination with thirst and/or reduced or darkened urine,
diarrhoea,
pain, including headache,
blood clots in the veins of the legs or difficulties in getting the blood to clot,
localised pus collection,
infection, and in particular infection in the blood or bladder,
reduced blood supply to the brain,
blood clots in the arteries, which can lead to a stroke and a heart attack,
falling asleep or fainting
problems with the heart with breathing difficulties,
increase in heart rate (pulse),
blockage in the gut or bowel,
abnormal urine test (protein in the urine),
shortness of breath or low levels of oxygen in the blood.

Rarely, such side effects as seizures (fits), headache, confusion or changes in vision may occur.

You should seek help immediately if you suffer from any of the above mentioned side effects.

The very common (more than 1 in 10 patients) side effects which were not severe, include:

high blood pressure,
pain,
lack of energy,
constipation, bleeding from the lower part of the large bowel, inflammation of the mouth,
loss of appetite,
protein in the urine,
nose bleed,
fever.

The common (up to 1 in 10 patients) side effects which were not severe, include:

shortness of breath,
nose bleed,
runny nose,
dry skin, flaking and inflammation of the skin, change in skin colour,
change in the sense of taste,
problems with eye (tearing).

Other less common side effects of any severity which have been reported are heart failure and bleeding from the lining of the mouth or vagina.

There have been very rare reports of patients developing a hole in the septum of the nose – the structure, which separates the nostrils.

Some side effects are more common in elderly patients. These side effects include blood clot in the arteries which can lead to a stroke or a heart attack. In addition, elderly patients have a higher risk of a reduction in the number of white cells in the blood.

You should seek help as soon as possible if you suffer from any of the above mentioned side effects.

Avastin may also cause changes in laboratory tests carried out by your doctor. These include; a decreased number of white cells in the blood, in particular neutrophils (one type of white blood cell which helps protect against infections) in the blood; presence of protein in the urine; decreased blood potassium, sodium or phosphorous (a mineral); increased blood sugar; increased blood alkaline phosphatase (an enzyme); decreased haemoglobin (found in red blood cells, which carry oxygen), which may be severe.

5. HOW TO STORE AVASTIN

Keep out of the reach and sight of children.

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Keep the vial in the outer carton.

Do not use after the expiry date which is stated on the outer carton and on the vial label after the abbreviation EXP. The expiry date refers to the last day of that month.

Infusion solutions should be used immediately after dilution. Discard any unused medicine.

6. FURTHER INFORMATION

What Avastin contains

The active substance is bevacizumab.
The other ingredients are trehalose dihydrate, sodium phosphate, polysorbate 20 and water for injections.

What Avastin looks like and contents of the pack

Avastin is a clear, colourless to pale brown liquid in a glass vial with a rubber stopper. Each vial contains 100 mg bevacizumab in 4 ml of solution or 400 mg bevacizumab in 16 ml of solution.

Medicine: avastin