For doctors
What is it and how is it used?
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.

Avastin is a medicine used for the treatment of advanced cancer in the large bowel, i.e., in the colon or rectum. Avastin will be administered in combination with chemotherapy treatment containing a fluoropyrimidine medicine.

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 drug called paclitaxel.

Avastin is also used for the treatment of advanced non-small cell lung cancer. Avastin will be administered together with a chemotherapy regimen containing platinum.

Avastin is also used for treatment of advanced kidney cancer. When used for patients with kidney cancer, it will be administered with another type of medicine called interferon.

What do you have to consider before using it?
Do not use Avastin if:

Take special care with Avastin:

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

Before you are given Avastin or while you are being treated with Avastin:

You may be advised to have a dental check-up before you start treatment with Avastin.

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.

Please tell your doctor if you have recently received, or are receiving, radiotherapy.

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.

How is it used?
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 mg, 7.5 mg, 10 mg 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 sodium chloride 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. If this is well-tolerated the second infusion may be given over 60 minutes. Later infusions may be given to you over 30 minutes.

The administration of Avastin should be temporarily discontinued

The administration of Avastin should be permanently discontinued if you develop

If too much Avastin is given

If a dose of Avastin is missed

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 medicine, ask your doctor or pharmacist.

What are 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.

These side effects may occur with certain frequencies, which are defined as follows:

Allergic reactions
If you have an allergic reaction, tell your doctor or a member of the medical staff straight away. The signs may include: difficulty in breathing or chest pain. You could also experience redness or flushing of the skin or a rash, increased muscle tension, feeling sick (nausea) or being sick (vomiting).

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

The common side effects are:

The severe side effects, which may be very common, include:

The severe side effects, which may be common, include:

The severe side effects, which may be rare, include:

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

The very common side effects, which were not severe, include:

The common side effects, which were not severe, include:

Other less common side effects of any severity which have been reported are heart failure, bleeding from the lining of the mouth or vagina, abnormal tube-like connection between internal organs and skin or other tissues that are not normally connected and ulcers in the digestive system (the signs may include abdominal pain, feeling bloated, black tarry stools or blood in your stools (faeces) or blood in your vomit).

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, and cells that help the blood clot. Other side effects reported with a higher frequency in elderly patients were diarrhoea, sickness, headache and fatigue.

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.

Pain in the mouth, teeth and/or jaw, swelling or sores inside the mouth, numbness or a feeling of heaviness in the jaw, or loosening of a tooth. These could be signs and symptoms of bone damage in the jaw (osteonecrosis). Tell your doctor and dentist immediately if you experience any of them.

Outside of the approved use of Avastin for cancer treatment, the following side effects may occur when Avastin is injected directly into the eye (unapproved use):

How should it be stored?
Keep out of the reach and sight of children.

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.

Store in a refrigerator (2°C–8°C).
Do not freeze.
Keep the vial in the outer carton in order to protect from light.

Infusion solutions should be used immediately after dilution. Do not use Avastin if you notice any particulate matter or discoloration prior to administration.

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.

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For doctors
What is it?
Avastin is a concentrate that is made up into a solution for infusion (drip into a vein). It contains the active substance bevacizumab.

What is it used for?
Avastin is used with other anticancer medicines to treat the following types of cancer:

The medicine can only be obtained with a prescription.

How is it used?
Avastin treatment should be supervised by a doctor who has experience in the use of cancer treatments.

The first infusion of Avastin should last 90 minutes, but subsequent infusions may be given over a shorter period if the first infusion is tolerated well. The dose is between 5 and 15 mg per kilogram body weight every two or three weeks, depending on the type of cancer being treated. The treatment is continued until the disease gets worse. The doctor may decide to interrupt or stop treatment if the patient develops certain side effects. See the summary of product characteristics (also part of the EPAR) for more information.

How does it work?
The active substance in Avastin, bevacizumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) in the body. Bevacizumab has been designed to attach to vascular endothelial growth factor (VEGF), a protein that circulates in the blood and makes blood vessels grow. By attaching to VEGF, Avastin stops it having an effect. As a result, the cancer cells cannot develop their own blood supply and are starved of oxygen and nutrients, helping to slow down the growth of tumours.

How has it been studied?
In cancer of the colon or rectum, the effects of adding Avastin to chemotherapy including a fluoropyrimidine have been studied in three main studies. The first two studies involved patients whose metastatic disease was being treated for the first time (‘first-line’ treatment): the first study (in 923 patients) and the second study (in 1,401 patients) compared Avastin with placebo (a dummy treatment) when given in combination with chemotherapy. The third study involved 829 patients who had failed previous treatment including a fluoropyrimidine and irinotecan (another anticancer medicine).

In breast cancer, Avastin has been studied in one main study which compared the effects of Avastin with paclitaxel to paclitaxel alone in 722 patients.

In lung cancer, Avastin has been studied in 878 patients. The study compared the effects of Avastin with platinum-based chemotherapy to chemotherapy alone.

In kidney cancer, Avastin has been studied in 649 patients with advanced or metastatic disease. The study compared Avastin with placebo when given in combination with interferon alfa-2a.

In all of the studies, the main measure of effectiveness was either overall survival or progression-free survival (how long the patients lived without their disease getting worse).

What benefits has it shown during the studies?
In cancer of the colon or rectum, Avastin increased both overall and progression-free survival when it was added to fluoropyrimidine-containing chemotherapy. In the first study of previously untreated patients, the average overall survival was 20.3 months in the patients adding Avastin and 15.6 months in those receiving chemotherapy alone. In the second study, progression-free survival was 9.4 months in the patients receiving Avastin and 8.0 months in those receiving placebo. In previously treated patients, overall survival was 13.0 months in the patients adding Avastin and 10.8 months in those receiving chemotherapy alone.

In breast cancer, adding Avastin also increased progression-free survival. When it was added to paclitaxel, the average progression-free survival was 11.4 months, compared with 5.8 months in those receiving paclitaxel alone.

In lung cancer, the average overall survival was 12.3 months in the patients taking Avastin with paclitaxel and carboplatin, and 10.3 months for those taking paclitaxel and carboplatin alone.

In kidney cancer, the average progression-free survival was 10.2 months in the patients receiving Avastin and 5.4 months in those receiving placebo.

What is the risk associated?
The most common side effects with Avastin (seen in more than 1 patient in 10) are neutropenia and febrile neutropenia (low white blood cell counts with or without fever), leucopenia (low white blood cell counts), thrombocytopenia (low blood platelet counts), peripheral sensory neuropathy (nerve damage in the hands and feet), hypertension (high blood pressure), diarrhoea, nausea (feeling sick), vomiting, asthenia (weakness), fatigue (tiredness), loss of appetite, dysgeusia (taste disturbances), headache, eye disorders, increased lacrimation (tear production), dyspnoea (difficulty breathing), epistaxis (nosebleeds), rhinitis (blocked nose), constipation, stomatitis (inflammation of the lining of the mouth), rectal haemorrhage (bleeding from the rectum), exfoliative dermatitis (flaky skin), dry skin, skin discoloration, arthralgia (joint pain), proteinuria (protein in the urine), pyrexia (fever), pain and mucosal inflammation (inflammation of the moist body surfaces). For the full list of all side effects reported with Avastin, see the package leaflet.

Avastin should not be used in people who may be hypersensitive (allergic) to bevacizumab or any of the other ingredients, to Chinese hamster ovary cell products or other recombinant antibodies. It must not be given to pregnant women.

Why has it been approved?
The CHMP decided that Avastin’s benefits are greater than its risks and recommended that it be given marketing authorisation.

In metastatic breast cancer, Avastin is approved for use in combination with paclitaxel. Formerly Avastin was also approved for use in combination with docetaxel (another anticancer medicine), but in December 2010 this indication was removed following a review of the relevant data.1

Further information
The European Commission granted a marketing authorisation valid throughout the European Union for Avastin to Roche Registration Limited on 12 January 2005. After five years, the marketing authorisation was renewed for a further five years. europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Avastin, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 02-2011.

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Name

Avastin 25 mg/ml concentrate for solution for infusion

Composition

Each ml contains 25 mg of bevacizumab.
Each vial contains 100 mg of bevacizumab in 4 ml and 400 mg in 16 ml respectively, corresponding to 1.4 to 16.5 mg/ml when diluted as recommended.

Bevacizumab is a recombinant humanised monoclonal antibody produced by DNA technology in Chinese Hamster ovary cells.

For a full list of excipients, see section 6.1.

Pharmaceutical Form

Concentrate for solution for infusion.

Clear to slightly opalescent, colourless to pale brown liquid.

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