Patient leaflet - ZIRABEV 100 MG / 4 ML CONCENTRATE FOR SOLUTION FOR INFUSION
1. what zirabev is and what it is used foreiejiueouoo |iu/6iu gg aeqejiz
Zirabev 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). 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. The VEGF protein causes blood vessels to grow within tumours, these blood vessels provide the tumour with nutrients and oxygen. Once bevacizumab is bound to VEGF, tumour growth is prevented by blocking the growth of the blood vessels which provide the nutrients and oxygen to the tumour.
Zirabev is a medicine used for the treatment of adult patients with advanced cancer in the large bowel, i.e., in the colon or rectum. Zirabev will be administered in combination with chemotherapy treatment containing a fluoropyrimidine medicine.
Zirabev is also used for the treatment of adult patients with metastatic breast cancer. When used for patients with breast cancer, it will be administered with a chemotherapy medicinal product called paclitaxel or capecitabine.
Zirabev is also used for the treatment of adult patients with advanced non-small cell lung cancer. Zirabev will be administered together with a chemotherapy regimen containing platinum.
Zirabev is also used for the treatment of adult patients with advanced non-small cell lung cancer when cancer cells have specific mutations of a protein called epidermal growth factor receptor (eGfR). Zirabev will be administered in combination with erlotinib.
Zirabev is also used for treatment of adult patients with advanced kidney cancer. When used for patients with kidney cancer, it will be administered with another type of medicine called interferon.
Zirabev is also used for the treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer. When used for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer, it will be administered in combination with carboplatin and paclitaxel.
When used for those adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease has come back at least 6 months after the last time they were treated with a chemotherapy regimen containing a platinum agent, Zirabev will be administered in combination with carboplatin and gemcitabine or with carboplatin and paclitaxel.
When used for those adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease has come back before 6 months after the last time they were treated with a chemotherapy regimen containing a platinum agent, Zirabev will be administered in combination with paclitaxel, or topotecan, or pegylated liposomal doxorubicin.
Zirabev is also used for the treatment of adult patients with persistent, recurrent or metastatic cervical cancer. Zirabev will be administered in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in patients who cannot receive platinum therapy.
2. what you need to know before you use zirabev
Do not use Zirabev
- if you are allergic (hypersensitive) to bevacizumab or to any of the other ingredients of this medicine (listed in section 6).
- if you are allergic (hypersensitive) to Chinese hamster ovary (CHO) cell products or to other recombinant human or humanised antibodies.
- if you are pregnant.
Warnings and precautions
Talk to your doctor, pharmacist or nurse before using Zirabev
- Your doctor should record the brand name and batch number of your medication.
- It is possible that Zirabev 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.
- Zirabev 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.
- This medicine 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.
- Zirabev 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.
- Zirabev 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 Zirabev treatment.
- If you have or have had an aneurysm (enlargement and weakening of a blood vessel wall) or a tear in a blood vessel wall.
- This medicine increases the risk of having protein in your urine especially if you already have high blood pressure.
- The risk of developing blood clots in your arteries (a type of blood vessel) can increase if you are over 65 years old, if you have diabetes, or if you have had previous blood clots in your arteries. Please talk to your doctor since blood clots can lead to heart attack and stroke.
- Zirabev can also increase the risk of developing blood clots in your veins (a type of blood vessel).
- This medicine may cause bleeding, especially tumour-related bleeding. Please consult your doctor if you or your family tend to suffer from bleeding problems or you are taking medicines to thin the blood for any reason.
- It is possible that Zirabev may cause bleeding in and around your brain. Please discuss this with your doctor if you have metastatic cancer affecting your brain.
- It is possible that Zirabev can increase the risk of bleeding in your lungs, including coughing or spitting blood. Please discuss with your doctor if you noticed this previously.
- Zirabev can increase the risk of developing a weak heart. It is important that your doctor knows 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, or if you have heart disease.
- This medicine may cause infections and a decreased number of your neutrophils (a type of blood cell important for your protection against bacteria).
- It is possible that Zirabev can cause hypersensitivity and/or infusion reactions (reactions related to your injection of the medicine). Please let your doctor, pharmacist or nurse know if you have previously experienced problems after injections, such as dizziness/feeling of fainting, breathlessness, swelling or skin rash.
- A rare neurological side effect named posterior reversible encephalopathy syndrome (PRES) has been associated with bevacizumab treatment. If you have headache, vision changes, confusion or seizure with or without high blood pressure, please contact your doctor.
Please consult your doctor, even if these above statements were only applicable to you in the past.
Before you are given Zirabev or while you are being treated with Zirabev:
- if you have or have had 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 tell your doctor and dentist immediately.
- if you need to undergo an invasive dental treatment or dental surgery, tell your dentist that you are being treated with Zirabev, in particular when you are also receiving or have received an injection of bisphosphonate into your blood.
You may be advised to have a dental check-up before you start treatment with Zirabev.
Children and adolescents
Zirabev use is not recommended in children and adolescents under the age of 18 years because the safety and benefit have not been established in these patient populations.
Death of bone tissue (osteonecrosis) in bones other than the jaw have been reported in patients under 18 years old when treated with bevacizumab.
Other medicines and Zirabev
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines.
Combinations of Zirabev with another medicine called sunitinib malate (prescribed for renal and gastrointestinal cancer) may cause severe side effects. Discuss with your doctor to make sure that you do not combine these medicines.
Tell your doctor if you are using platinum- or taxane-based therapies for lung or metastatic breast cancer. These therapies in combination with Zirabev may increase the risk of severe side effects.
Please tell your doctor if you have recently received, or are receiving, radiotherapy.
Pregnancy, breast-feeding and fertility
You must not use this medicine if you are pregnant. Zirabev 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 Zirabev and for at least 6 months after the last dose of Zirabev.
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 Zirabev and for at least 6 months after the last dose of Zirabev, as this medicine may interfere with the growth and development of your baby.
Zirabev may impair female fertility. Please consult your doctor for more information.
Ask your doctor, pharmacist or nurse for advice before taking any medicine.
Driving and using machines
Bevacizumab has not been shown to reduce your ability to drive or to use any tools or machines. However, sleepiness and fainting have been reported with bevacizumab use. If you experience symptoms that affect your vision or concentration, or your ability to react, do not drive and use machines until symptoms disappear.
Zirabev contains sodium
This medicine contains 3.0 mg sodium (main component of cooking/table salt) in each 4 ml vial. This is equivalent to 0.15% of the recommended maximum daily dietary intake of sodium for an adult.
This medicine contains 12.1 mg sodium (main component of cooking/table salt) in each 16 ml vial. This is equivalent to 0.61% of the recommended maximum daily dietary intake of sodium for an adult.
Depending on your body weight and your dose of Zirabev, you could receive multiple vials. This should be taken into consideration if you are on a low salt diet.
3. how to use zirabev
Dose and frequency of administration
The dose of Zirabev 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 Zirabev that is right for you. You will be treated with Zirabev 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 Zirabev fails to stop your tumour growing. Your doctor will discuss this with you.
Method and route of administration
Zirabev is a concentrate for solution for infusion. Depending on the dose prescribed for you, some or all of the contents of the Zirabev vial will be diluted with sodium chloride solution before use. A doctor or nurse will give you this diluted Zirabev 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 Zirabev 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 Zirabev 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,
- any severe bleeding.
If too much Zirabev is given
- you may develop a severe migraine. If this happens you should talk to your doctor, pharmacist or nurse immediately.
If a dose of Zirabev is missed
- your doctor will decide when you should be given your next dose of Zirabev. You should discuss this with your doctor.
If you stop treatment with Zirabev
Stopping your treatment with Zirabev may stop the effect on tumour growth. Do not stop treatment with Zirabev unless you have discussed this with your doctor.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.
4. possible side effects
blood clot in the arteries which can lead to a stroke or a heart attack,
5. how to store zirabev
Keep this medicine out of the sight and reach of children.
Do not use this medicine 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. 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, Zirabev is stable for a period of up to 35 days at 2°C to 8°C after dilution and a period of up to 48 hours at temperatures not exceeding 30°C. Do not use Zirabev if you notice any particulate matter or discolouration prior to administration.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.
6. contents of the pack and other information
What Zirabev contains
- The active substance is bevacizumab. Each ml of concentrate contains 25 mg of bevacizumab.
Each 4 ml vial contains 100 mg of bevacizumab.
Each 16 ml vial contains 400 mg of bevacizumab.
- The other ingredients are sucrose, succinic acid, disodium edetate, polysorbate 80, sodium hydroxide (for pH adjustment), and water for injections (see section 2 “Zirabev contains sodium”).
What Zirabev looks like and contents of the pack
Zirabev is a concentrate for solution for infusion. The concentrate is a clear to slightly opalescent, 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. Each pack of Zirabev contains one vial.
Marketing Authorisation Holder
Pfizer Limited, Ramsgate Road, Sandwich, Kent, CT13 9NJ,
United Kingdom
Manufacturer
Pfizer Service Company BV, Hoge Wei 10, Zaventem, 1930, Belgium
For any information about this medicine, please contact:
Medical Information, Pfizer Ltd, Walton Oaks, Dorking Road, Tadworth, Surrey, KT20 7NS.
Telephone 01304 616161