Bevacizumab Solution

What BEVACIZUMAB EQUITY is
BEVACIZUMAB EQUITY contains the active substance bevacizumab, which is a humanised monoclonal antibody (a type of protein that is normally made by the immune system to help defend the body from infection and cancer).

What BEVACIZUMAB EQUITY is used for
BEVACIZUMAB EQUITY is used for the treatment of adult patients with:

• Advanced cancer in the large bowel, i.e., in the colon or rectum. BEVACIZUMAB EQUITY will be administered in combination with chemotherapy treatment containing a fluoropyrimidine medicine.
• Metastatic breast cancer. When used for patients with breast cancer, BEVACIZUMAB EQUITY will be administered with a chemotherapy medicine called paclitaxel.
• Advanced, metastatic and recurrent adenocarcinoma of the lung. BEVACIZUMAB EQUITY will be administered together with a chemotherapy regimen containing platinum.
• Advanced, metastatic kidney cancer. When used for patients with kidney cancer, it will be administered with another type of medicine called interferon.

BEVACIZUMAB EQUITY should not be administered to you if:

• you are hypersensitive (allergic) to bevacizumab or to any of the other ingredients of BEVACIZUMAB EQUITY (listed in section 6)
• you are hypersensitive (allergic) to Chinese hamster ovary (CHO) cell products or to other recombinant human or humanised antibodies
• you are pregnant or breastfeeding your baby
• you have untreated cancer that has spread from the original tumour to the central nervous system.

BEVACIZUMAB EQUITY must not be administered together with a medicine called sunitinib. It must also not be injected into the eye.

Warnings and precautions

Talk to your doctor or healthcare professional before being given BEVACIZUMAB EQUITY.

• It is possible that BEVACIZUMAB EQUITY may increase the risk of developing holes in the gut wall. If you have conditions causing inflammation inside the abdomen (e.g. diverticulitis, stomach ulcers, colitis associated with chemotherapy), please discuss this with your doctor.
• BEVACIZUMAB EQUITY may increase the risk of developing an abnormal connection or passageway between two organs or vessels. The risk of developing connections between the vagina and any parts of the gut can increase if you have persistent, recurrent or metastatic cervical cancer.
• BEVACIZUMAB EQUITY can increase the risk of bleeding or increase the risk of problems with wound healing after surgery. 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.
• BEVACIZUMAB EQUITY may increase the risk of developing serious infections of the skin or deeper layers under the skin, especially if you had holes in the gut wall or problems with wound healing.
• BEVACIZUMAB EQUITY can increase the incidence of high blood pressure. If you have high blood pressure which is not well controlled with blood pressure medicines, please consult your doctor as it is important to make sure that your blood pressure is under control before starting BEVACIZUMAB EQUITY treatment.

You will not be expected to give yourself BEVACIZUMAB EQUITY. It will be given to you by a person who is qualified to do so. They will watch you closely while you are being given BEVACIZUMAB EQUITY. This is in case you get any side effects.

Dosage and frequency of administration

The dose of BEVACIZUMAB EQUITY 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 BEVACIZUMAB EQUITY that is right for you. You will be treated with BEVACIZUMAB EQUITY 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 BEVACIZUMAB EQUITY until it fails to stop your tumour growing. Your doctor will discuss this with you.

Method and route of administration

BEVACIZUMAB EQUITY is a concentrate for solution for infusion. Depending on the dose prescribed for you, some or all of the contents of the BEVACIZUMAB EQUITY vial will be diluted with sodium chloride solution before use. A doctor or nurse will give you this diluted BEVACIZUMAB EQUITY solution by intravenous infusion (a drip into your vein). 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 BEVACIZUMAB EQUITY 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, or if you undergo surgery.

The administration of BEVACIZUMAB EQUITY 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, an abnormal tube-like connection or passage between the windpipe and the gullet, between internal organs and skin, between the vagina and any parts of the gut or between other tissues that are not normally connected (fistula), and are judged by your doctor to be severe, serious infections of the skin or deeper layers under the skin, a blood clot in your arteries, a blood clot in the blood vessels of your lungs, or any severe bleeding.

BEVACIZUMAB EQUITY can have side effects. Not all side effects reported for BEVACIZUMAB EQUITY are included in this leaflet. Should your general health worsen or if you experience any untoward effects while being treated with BEVACIZUMAB EQUITY, please consult healthcare provider for advice.

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

If any of the following happens, stop using BEVACIZUMAB EQUITY and tell your doctor immediately or go to the casualty department at your nearest hospital:

• swelling of the hands, feet, ankles, face, lips and mouth or throat, which may cause difficulty in swallowing or breathing,
• rash or itching,
• fainting,
• chills or shivering,
• feeling sick (nausea) or being sick (vomiting).

These are all very serious side effects. If you have them, you may have had a serious reaction to BEVACIZUMAB EQUITY. You may need urgent medical attention or hospitalisation.

You should seek help immediately if you suffer from any of the below mentioned side effects. Severe side effects, which may be frequent, include:

• high blood pressure,
• feeling of numbness or tingling in hands or feet,
• decreased number of cells in the blood, including white cells that help to fight against infections (this may be accompanied by fever), and cells that help the blood to clot,
• feeling weak and having no energy,
• tiredness,
• diarrhoea, nausea, vomiting and abdominal pain,
• 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,
• blocking of the veins by a blood clot,
• blocking of the blood vessels of the lungs by a blood clot,
• blocking of the veins of the legs by a blood clot,
• heart failure,
• problems with wound healing after surgery,
• redness, peeling, tenderness, pain, or blistering on the fingers or feet,
• decreased number of red cells in the blood,
• lack of energy,
• stomach and intestinal disorder,
• muscle and joint pain, muscular weakness,
• dry mouth in combination with thirst and/or reduced or darkened urine,
• inflammation of the moist lining of mouth and gut, lungs and air passages, reproductive, and urinary tracts,
• sores in the mouth and the tube from the mouth to the stomach, which may be painful and cause difficulty swallowing,
• pain, including headache, back pain and pain in the pelvis and anal regions,
• localised pus collection,
• infection, and in particular infection in the blood or bladder,
• reduced blood supply to the brain or stroke,
• sleepiness,
• nose bleed,
• 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,
• infections of the skin or deeper layers under the skin,
• fistula: abnormal tube-like connection between internal organs and skin or other tissues that are not normally connected, including connections between vagina and the gut in patients with cervical cancer.

Severe side effects of unknown frequency, include:

• serious infections of the skin or deeper layers under the skin, especially if you had holes in the gut wall or problems with wound healing,
• allergic reactions (the signs may include difficulty breathing, facial redness, rash, low blood pressure or high blood pressure, low oxygen in your blood, chest pain, or nausea/vomiting),
• a negative effect on a woman’s ability to have children (see the paragraphs below the list of side effects for further recommendations),
• a brain condition with symptoms including seizures (fits), headache, confusion, and changes in vision (Posterior Reversible Encephalopathy Syndrome or PRES),
• symptoms that suggest changes in normal brain function (headaches, vision changes, confusion, or seizures), and high blood pressure,
• an enlargement and weakening of a blood vessel wall or a tear in a blood vessel wall (aneurysms and artery dissections),
• clogging of a very small blood vessel(s) in the kidney,
• abnormally high blood pressure in the blood vessels of the lungs which makes the right side of the heart work harder than normal,
• a hole in the cartilage wall separating the nostrils of the nose,
• a hole in the stomach or intestines,
• an open sore or hole in the lining of the stomach or small intestine (the signs may include abdominal pain, feeling bloated, black tarry stools or blood in your stools (faeces) or blood in your vomit),
• bleeding from the lower part of the large bowel,
• lesions in the gums with an exposed jaw bone that does not heal and may be associated with pain and inflammation of the surrounding tissue (see the paragraphs below the list of side effects for further recommendations),
• hole in the gall bladder (symptoms and signs may include abdominal pain, fever, and nausea/vomiting).

You should seek help as soon as possible if you suffer from any of the below mentioned side effects. Frequent side effects, which were not severe, include:

• constipation,
• loss of appetite,
• fever,
• problems with the eyes (including increased production of tears),
• changes in speech,
• change in the sense of taste,
• runny nose,
• dry skin, flaking and inflammation of the skin, change in skin colour,
• loss of body weight,
• nose bleeds.
• voice changes and hoarseness.

Patients older than 65 years have an increased risk of experiencing the following side effects:

• blood clot in the arteries which can lead to a stroke or a heart attack,
• reduction in the number of white cells in the blood, and cells that help the blood clot,
• diarrhoea,
• sickness,
• headache,
• fatigue,
• high blood pressure.

BEVACIZUMAB EQUITY 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); increased serum creatinine (a protein measured by a blood test to see how well your kidneys are working); 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.

Pre-menopausal women (women who have a menstrual cycle) may notice that their periods become irregular or are missed and may experience impaired fertility. If you are considering having children you should discuss this with your doctor before your treatment starts.

• Store all medicines out of reach of children.
• Store in a refrigerator (2 °C – 8 °C).
• Do not freeze.
• Keep the container in the outer carton in order to protect from light.
• Infusion solutions should be used immediately after dilution. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2 °C to 8 °C, unless the infusion solutions have been prepared in a sterile environment. When dilution has taken place in a sterile environment, BEVACIZUMAB EQUITY is stable for 48 hours at 2 °C to 30 °C.
• Do not use BEVACIZUMAB EQUITY if you notice any particulate matter or discolouration prior to administration.
• Do not use this medicine after the expiry date which is stated on the carton and the vial after “EXP”. The expiry date refers to the last day of that month.
• Return all unused medicine to your pharmacist.
• Do not dispose of unused medicine in drains or sewerage systems (e.g. toilets).