25 mg / ml concentrate for solution for infusion
bevacizumab
What MVASI is and what it is used for
MVASI contains the active ingredient bevacizumab, which is a humanized monoclonal antibody (a type of protein normally produced by the immune system to help protect the body against infections and cancer). Bevacizumab selectively binds to a protein called VEGF ( human vascular endothelial growth factor), which is found inside the body’s blood and lymph vessels. VEGF protein causes blood vessels to grow in tumors and these blood vessels supply the tumor with nutrients and oxygen. When bevacizumab is bound to VEGF, the growth of the tumor is prevented by the growth of the blood vessels that supply the tumor with nutrients, and oxygen is blocked.
MVASI is a drug used to treat adult patients with advanced colon or rectal cancer. MVASI is given together with chemotherapy containing fluoropyrimidine.
MVASI is also used to treat adult patients with metastatic (spread) breast cancer. When used in patients with breast cancer, it is given together with a cytostatic drug called paclitaxel or capecitabine.
MVASI is also used to treat adult patients with advanced non-small-cell lung cancer. MVASI is then given together with a chemotherapy treatment that contains platinum.
MVASI is also used to treat adult patients with advanced non-small-cell lung cancer when the cancer cells have a specific mutation in a protein called the epidermal growth factor receptor (EGFR). MVASI is then given together with erlotinib.
MVASI is also used to treat adult patients with advanced kidney cancer. When MVASI is used in patients with kidney cancer, it is given together with another type of medicine called interferon.
MVASI is also used to treat adult patients with advanced ovarian, fallopian tubes, or primary peritoneal cancer. In the treatment of patients with ovarian, fallopian tube, or primary peritoneal cancer, MVASI is given in combination with carboplatin and paclitaxel.
When used in adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer whose disease has returned at least 6 months after the last time they were treated with a platinum-containing chemotherapy drug, MVASI is given in combination with carboplatin and gemcitabine or with carboplatin and paclitaxel.
When used in adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer whose disease has returned earlier than 6 months after the last time they were treated with a platinum-containing chemotherapy drug, MVASI is given in combination with paclitaxel, or topotecan, or pegylated liposomal doxorubicin.
MVASI is also used to treat adult patients with residual, recurrent, or metastatic cervical cancer. MVASI is then given in combination with paclitaxel and cisplatin or paclitaxel and topotecan in patients who are unable to receive platinum therapy.
What you need to know before using MVASI
Do not use MVASI
- if you are allergic (hypersensitive) to bevacizumab or any of the other ingredients of this medicine (listed in section 6).
- if you are allergic (hypersensitive) to products from Chinese hamster ovary (CHO) cells or recombinant human or humanized antibodies .
- if you are pregnant.
Warnings and cautions
Talk to your doctor, pharmacist, or nurse before using MVASI.
- It is possible that MVASI may increase the risk of developing holes in the intestinal wall. If you have diseases that cause inflammation inside the abdomen (eg diverticulitis , stomach ulcers , colitis associated with chemotherapy), tell your doctor.
- MVASI may increase the risk of developing an abnormal connection or passage between two organs or blood vessels (such a connection is called a fistula ). The risk of developing connections between the vagina and any part of the bowel may increase if you have residual, recurrent or metastatic cervical cancer.
- MVASI may increase the risk of bleeding, or increase the risk of problems with wound healing after surgery. If you are going to have surgery, if you have undergone major surgery within the last 28 days or if you still have unhealed surgical wounds, you should not use this medicine.
- MVASI can increase the risk of developing a serious infection of the skin or underlying layers of the skin, especially if you have had a hole in the intestinal wall or problems with wound healing.
- MVASI may increase the incidence of high blood pressure . If you suffer from high blood pressure that is not well controlled by blood pressure medication, talk to your doctor as it is important to ensure that your blood pressure is under control before starting treatment with MVASI.
- MVASI increases the risk of getting protein in your urine, especially if you already suffer from high blood pressure .
- The risk of getting blood clots in your arteries (a type of blood vessel) can increase if you are over 65, if you have diabetes , or if you have previously had blood clots in your arteries . Talk to your doctor as blood clots can lead to heart attack and stroke .
- MVASI can also increase the risk of developing blood clots in your veins (a type of blood vessel).
- MVASI can cause bleeding, especially tumor-related bleeding. Talk to your doctor if you or your family seem to be suffering from bleeding problems or if for any reason you are taking medication to thin the blood.
- It is possible that MVASI can cause bleeding in and around your brain. Discuss this with your doctor if you have a widespread cancer that affects your brain.
- It is possible that MVASI may increase the risk of bleeding in your lungs, including coughing and spitting blood. Talk to your doctor if you have noticed this before.
- MVASI may increase the risk of developing a weak heart. It is important that your doctor knows if you have ever received anthracyclines (eg doxorubicin, a special type of chemotherapy used to treat certain cancers) or have had radiation therapy to your chest, or if you have heart disease.
- MVASI can cause infections and a decrease in the number of neutrophils (a type of blood cell that is important for your protection against bacteria).
- It is possible that MVASI may cause hypersensitivity and / or infusion reactions (reactions related to your injection of this medicine). Tell your doctor, pharmacist or nurse if you have previously had problems after injections , such as dizziness / fainting, shortness of breath, swelling or rash.
- A rare neurological adverse reaction known as posterior reversible encephalopathy syndrome (PRES) has been associated with MVASI treatment. If you have headaches, vision changes, confusion or seizures with or without high blood pressure , consult your doctor.
- If you have or have had an aneurysm (enlargement and weakening of a vessel wall) or a rupture in a vessel wall.
Consult a doctor even if any of the above only applied to you earlier in your life.
Before you receive MVASI or while you are being treated with MVASI:
- If you have or have had pain in your mouth, teeth and / or jaw, swelling or soreness inside your mouth, numbness or a feeling of heaviness in your jaw, or if a tooth becomes loose, talk to your doctor and dentist immediately.
- If you need dental treatment or dental surgery, tell your dentist that you are being treated with MVASI (bevacizumab), especially if you are also receiving or have received intravenous bisphosphonates .
You may be advised to have your teeth examined before starting treatment with MVASI.
Children and young people
The use of MVASI in children and adolescents under 18 years of age is not recommended as safety and benefit have not been established in these patient groups.
Bone tissue death ( osteonecrosis ) in bones other than the jaw has been reported in patients under 18 years of age treated with bevacizumab.
Other medicines and MVASI
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
The combination of MVASI and another medicine called sunitinib malate (prescribed for cancer of the kidneys and gastrointestinal tract) can cause serious side effects. Talk to your doctor to make sure you are not combining these medicines.
Tell your doctor if you use platinum- or taxane-based treatment for lung or spread breast cancer. These treatments in combination with MVASI may increase the risk of serious side effects.
Tell your doctor if you have recently received, or are receiving, radiation therapy.
Pregnancy, breastfeeding and fertility
You must not use MVASI if you are pregnant. MVASI can harm your unborn baby as it can prevent the formation of new blood vessels. Your doctor will advise you to use contraception during treatment with MVASI and for at least 6 months after the last dose of one of MVASI.
Tell your doctor immediately if you are pregnant, become pregnant during treatment with this medicine, or plan to become pregnant shortly.
You must not breastfeed during treatment with MVASI and for at least 6 months after the last dose of one of MVASI as this medicine may interfere with your baby’s growth and development.
MVASI can impair female fertility. Contact your doctor for more information.
Consult a doctor, pharmacist, or nurse before taking any medicine.
Driving and using machines
MVASI has not been shown to reduce the ability to drive or use tools or machines. However, drowsiness and fainting have been reported with the use of MVASI. If you experience symptoms that affect your vision, concentration, or ability to react, do not drive or use machines until the symptoms have disappeared.
MVASI contains sodium
MVASI 25 mg / ml concentrate for solution for infusion (4 ml)
This medicine contains 5.4 mg of sodium (the main ingredient in table salt/table salt) per 4 ml vial. This corresponds to 0.3% of the maximum recommended daily intake of sodium for adults.
MVASI 25 mg / ml concentrate for solution for infusion (16 ml)
This medicine contains 21.7 mg sodium (the main ingredient in table salt/table salt) per 16 ml vial. This corresponds to 1.1% of the highest recommended daily intake of sodium for adults.
How to use MVASI
Dosage and dosing frequency
Dose one of MVASI depends on your body weight and the type of cancer to be treated. The recommended dose is 5 mg, 7.5 mg, 10 mg, or 15 mg per kg of your body weight. Your doctor will prescribe the MVASI dose that is right for you. You will be treated with MVASI once every two or three weeks. The number of infusions you receive depends on how you respond to the treatment; you should continue to use this medicine until MVASI can no longer prevent your tumor from growing. Your doctor will discuss this with you.
Method of administration
MVASI is a concentrate for infusion solution. Depending on the dose prescribed by your doctor, some or all of the contents of the MVASI vial will be diluted with sodium chloride (saline) solution before use. A doctor or nurse will give you the diluted MVASI solution as an intravenous infusion (a drip into a vein). The first infusion will be given over 90 minutes. If you tolerate this well, the second infusion will be given for 60 minutes. Later infusions can be given for 30 minutes.
MVASI treatment should be temporarily discontinued
- if you develop severe high blood pressure that requires treatment with blood pressure medication,
- if you have problems with wound healing after surgery,
- if you are having surgery.
Treatment with MVASI should be stopped completely if you develop
- severe high blood pressure that can not be controlled with blood pressure medication; or a sudden increase in blood pressure,
- protein in the urine and at the same time swelling in the body,
- a hole in your intestinal wall,
- an abnormal tubular connection or passage between the trachea and esophagus, between internal organs and the skin, between the vagina and any part of the intestine or between other tissues that should not normally be connected to each other ( fistula ), and which your doctor considers serious,
- severe infection of the skin or underlying layers of the skin,
- a blood clot in your arteries ,
- a blood clot in the blood vessels of the lungs,
- any severe bleeding.
If you take more MVASI than you should
- you may develop severe migraines . If this happens, talk to your doctor, pharmacist or nurse immediately.
If you miss a dose of MVASI
- your doctor will decide when you should receive your next dose of MVASI . You should discuss this with your doctor.
If you stop using MVASI
If you stop your treatment with MVASI, the effect on tumor growth may cease. Do not stop treatment with MVASI unless you have discussed this with your doctor.
If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.
Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you get any side effects, talk to your doctor, pharmacist, or nurse. This also applies to any side effects not mentioned in this information.
The side effects listed below were seen when MVASI was co-administered with chemotherapy drugs. This does not necessarily mean that these side effects are caused by MVASI.
Allergic reactions
If you get an allergic reaction, tell your doctor or healthcare professional immediately. These signs may include difficulty breathing or chest pain. You may also get redness on the skin or rash, chills, tremors, nausea, or vomiting.
You should seek immediate help if you get any of the side effects listed below.
The serious side effects, which can be very common (may affect more than 1 in 10 people), include:
- high blood pressure ,
- feeling of numbness or tingling in the hands or feet,
- decreased number of blood cells in the blood, including white blood cells that help protect against infection (this can occur along with fever), and platelets that help the blood to clot,
- feeling weak and lacking in energy,
- fatigue,
- diarrhea, nausea, vomiting and abdominal pain.
The serious side effects, which can be common (may affect up to 1 in 10 people), include:
- holes in the intestine,
- haemorrhage, including haemorrhage in the lungs of patients with non- small cell lung cancer ,
- blockage of the arteries with a blood clot,
- blockage of the veins with a blood clot,
- blockage of the blood vessels in the lungs with a blood clot,
- blockage of the veins in the legs with a blood clot,
- heart failure ,
- problems with wound healing after surgery,
- redness, scaly skin, tenderness, pain, or blisters on fingers or feet,
- decreased number of red blood cells in the blood,
- lack of energy,
- gastrointestinal problems,
- muscle and joint pain, muscle weakness,
- dry mouth in combination with thirst and / or decreased or dark-colored urine,
- inflammation of the mucous membranes of the mouth and stomach, lungs and respiratory tract, reproductive organs and urinary tract,
- sores in the mouth and esophagus, which can be painful and cause difficulty swallowing,
- pain, including headache, back pain and pain in the pelvis and anal region,
- localized warp formation,
- infection , and in particular infection of the blood or bladder,
- decreased blood supply to the brain, or stroke (blood clot in the brain or cerebral hemorrhage),
- somnolence,
- nosebleed,
- increase in heart rate ( pulse one),
- blocked gastrointestinal passage,
- abnormal urine samples ( protein in the urine),
- shortness of breath or low oxygen levels in the blood,
- skin infections or infection are in the deeper layers under the skin,
- fistula: an abnormal tubular connection between internal organs and skin or other tissues that are not normally connected to each other, including connections between the vagina and the intestine in patients with cervical cancer.
Serious side effects with an unknown frequency (cannot be calculated from the available data) include:
- severe infections of the skin or deeper layers under the skin, especially if you have had holes in the abdominal wall or problems with wound healing,
- allergic reactions (signs may include difficulty breathing, flushing, rash, low or high blood pressure , low blood oxygen level, chest pain, or nausea / vomiting),
- a negative effect on women’s ability to have children (see section after the list of side effects for further recommendations),
- a condition of the brain with symptoms that include seizures (seizures), headaches, confusion and changes in vision (posterior reversible encephalopathy syndrome or PRES),
- signs indicating changes in normal brain function (headache, vision changes, confusion or seizures) and high blood pressure ,
- blood clots in very small blood vessels in the kidney,
- abnormally high blood pressure in the blood vessels in the lungs, which causes the right side of the heart to work harder than normal,
- a hole in the septum (the cartilage wall that separates the nostrils) in the nose,
- a hole in the stomach or intestine,
- an open wound or hole in the lining of the stomach or small intestine (signs may include abdominal pain, feeling of bloating, black tarry stools or blood in the stools or bloody vomiting),
- bleeding from the lower part of the colon,
- gums in the gums with an exposed jawbone that does not heal and may be associated with pain and inflammation in the surrounding tissue (see section after the list of side effects for further recommendations),
- holes in the gallbladder (symptoms and signs may include abdominal pain, fever and nausea / vomiting),
- an enlargement and weakening of a vessel wall or a rupture in a vessel wall ( aneurysms and arterial dissections).
You should seek help as soon as possible if you get any of the following side effects.
The very common (may affect more than 1 in 10 people) side effects, which were not serious, include:
- constipation,
- loss of appetite,
- fever,
- eye problems (including increased tear flow),
- speech disorders,
- change of taste,
- Runny nose,
- dry skin, scaly skin and inflammation of the skin, change in skin color,
- weight loss,
- nosebleeds.
The common (may affect up to 1 in 10 people) side effects, which were not serious, include:
- voice change and hoarseness.
Patients older than 65 years have an increased risk of experiencing the following side effects:
- blood clots in the arteries that can lead to stroke (blood clot or cerebral hemorrhage) or heart attack,
- reduction in the number of white blood cells in the blood and reduction in the number of platelets that help the blood to clot,
- diarrhea,
- feeling sick,
- headache,
- fatigue,
- high blood pressure .
MVASI can also cause changes in laboratory tests performed by your doctor. These include decreased white blood cell counts, especially neutrophils (a type of white blood cell that helps protect against infections ) in the blood, protein in the urine, decreased levels of potassium, sodium, or phosphorus (a mineral) in the blood, high blood sugar, elevated alkaline phosphatase (an enzyme ) in the blood, elevated serum creatinine (a protein measured by a blood test to check how your kidneys are working), decreased hemoglobin (found in red blood cells and carrying oxygen), which can be serious.
Pain in the mouth, teeth, and/or jaw, swelling or tenderness inside the mouth, numbness or a feeling of heaviness in the jaw, or that a tooth becomes loose. These may be signs and symptoms of damage to the jawbone ( osteonecrosis ). Tell your doctor and dentist immediately if you experience any of them.
Fertile women (women who have a regular menstrual cycle) may notice that their period becomes irregular or absent and may notice impaired fertility. If you are considering having children, discuss this with your doctor before starting treatment.
MVASI has been developed and manufactured to treat cancer by injection into the bloodstream. It has not been developed or manufactured for injection into the eye. It is therefore not approved for use in this way. When bevacizumab is injected directly into the eye (unauthorized use) the following side effects may occur:
- infection or inflammation of the eyeball,
- redness of the eye, small particles or dots / spots in the field of vision , eye pain,
- to see flashes of light in connection with dots / spots that develop into a certain loss of vision,
- increased pressure in the eye,
- bleeding in the eye.
How to store MVASI
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 carton and the label of the vial after the abbreviation EXP. The expiration date is the last day of the specified month.
Store in a refrigerator (2 ° C ‑ 8 ° C).
Do not freeze.
Keep the vial in the outer carton. Sensitive to light.
Infusion solutions should be used immediately after dilution. If it is not used immediately, the responsibility for shelf life and storage lies with the user. This storage should normally not be longer than 24 hours at 2 ° C to 8 ° C unless the solution has been prepared in a sterile environment. Once diluted in a sterile environment, MVASI is stable for 35 days at 2 ° C to 8 ° C plus a further 48 hours at temperatures not exceeding 30 ° C.
Do not use MVASI if you see particles or discoloration before 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.
Contents of the pack and other information
Content declaration
- The active substance is bevacizumab. Each ml of concentrate contains 25 mg of bevacizumab, equivalent to 1.4 to 16.5 mg / ml when diluted as recommended.Each 4 ml vial contains 100 mg of bevacizumab, equivalent to 1.4 mg / ml when diluted as recommended.Each 16 ml vial contains 400 mg of bevacizumab, equivalent to 16.5 mg / ml when diluted as recommended.
- The other ingredients are trehalose dihydrate, sodium phosphate, polysorbate and water for injections.
What the medicine looks like and contents of the pack
MVASI is a concentrated solution for infusion. The concentrate is a clear to slightly opalescent, colorless to slightly yellowish liquid in a glass vial with a rubber stopper. Each vial contains 100 mg bevacizumab in 4 ml solution or 400 mg bevacizumab in 16 ml solution. Each MVASI pack contains one vial.
Marketing Authorization Holder and Manufacturer
Amgen Technology (Ireland) UC,
Pottery Road,
Dun Laoghaire,
Co. Dublin,
Ireland