25 mg / ml concentrate for solution for infusion
bevacizumab
What Oyavas is and what it is used for
Oyavas contains the active substance 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 blocking the growth of the blood vessels that supply the tumor one with nutrients and oxygen.
Oyavas is a drug used to treat adult patients with advanced colon or rectal cancer. Oyavas is given in combination with chemotherapy containing fluoropyrimidine.
Oyavas is also used to treat adult patients with metastatic (spread) breast cancer. When used in patients with breast cancer, it will be given with a cytostatic drug called paclitaxel or capecitabine.
Oyavas is also used to treat adult patients with advanced non-small-cell lung cancer. Oyavas is then given together with a chemotherapy treatment that contains platinum.
Oyavas 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 epidermal growth factor receptor (EGFR). Oyavas is then given together with erlotinib.
Oyavas is also used to treat adult patients with advanced kidney cancer. When Oyavas is used in patients with kidney cancer, it will be given together with another type of medicine called interferon.
Oyavas is also used to treat adult patients with advanced ovarian, fallopian tubes, or primary peritoneal cancer. In the treatment of patients with ovarian, fallopian tubes, or primary peritoneal cancer, Oyavas should be given in combination with carboplatin and paclitaxel.
When used in adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer whose disease has returned at least 6 months after the last time they were treated with platinum-containing chemotherapy, Oyavas will be 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 platinum-containing chemotherapy, Oyavas will be given in combination with topotecan or pegylated liposomal doxorubicin.
Oyavas is also used to treat adult patients with persistent, recurrent, or metastatic cervical cancer. Oyavas 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 Oyavas
Do not use Oyavas
- if you are allergic to bevacizumab or any of the other ingredients of this medicine (listed in section 6).
- if you are allergic 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 Oyavas.
- Oyavas 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.
- Oyavas can 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 intestine may increase if you have residual, recurrent, or metastatic cervical cancer.
- Oyavas 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.
- Oyavas can increase the risk of developing a serious infection in your skin or underlying layers of the skin, especially if you have had a hole in the intestinal wall or problems with wound healing.
- Oyavas can 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 make sure your blood pressure is under control before starting treatment with Oyavas.
- If you have or have had an aneurysm (enlargement and weakening of a vessel wall) or a rupture in a vessel wall.
- Oyavas 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.
- Oyavas can also increase the risk of developing blood clots in your veins (a type of blood vessel).
- Oyavas can cause bleeding, especially tumor-related bleeding. Talk to your doctor if you or your family tend to suffer from bleeding problems or if for any reason you are taking medication to thin your blood.
- Oyavas can cause bleeding in and around your brain. Discuss this with your doctor if you have widespread cancer that affects your brain.
- Oyavas can increase the risk of bleeding in your lungs, including coughing and spitting blood. Talk to your doctor if you have noticed this before.
- Oyavas may increase the risk of developing a weak heart. Your doctor needs to know if you have ever been given anthracyclines (eg doxorubicin, a special type of chemotherapy used to treat certain cancers) or received radiation therapy to your chest, or if you have heart disease.
- Oyavas can cause infections and a decrease in the number of neutrophils (a type of blood cell that is important for your protection against bacteria).
- Oyavas 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 side effect called posterior reversible encephalopathy syndrome (PRES) has been associated with Oyavas treatment. If you have headaches, vision changes, confusion, or seizures with or without high blood pressure, consult your doctor.
- Bone tissue death ( osteonecrosis ) in bones other than the jaw has been reported in patients under 18 years of age treated with Oyavas. Pain in the mouth, teeth, and/or jaw, swelling or tenderness inside the mouth, numbness or a feeling of heaviness in the jaw, or if a tooth becomes loose, can be signs or symptoms of bone damage in the jaw (osteonecrosis). Tell your doctor and dentist immediately if you experience any of them.
Contact your doctor even if these statements above only applied to you earlier in your life.
Before you receive Oyavas or while you are being treated with Oyavas:
- 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 Oyavas, especially if you are also receiving or have received intravenous bisphosphonates.
You may be advised to have your teeth examined before starting treatment with Oyavas.
Oyavas have 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 Oyavas 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, which turns into a certain loss of vision,
- Increased pressure in the eye,
- Bleeding in the eye.
Children and young people
The use of Oyavas in children and adolescents under 18 years of age is not recommended as safety and benefit have not been established in these patient groups.
Other medicines and Oyavas
Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Combining Oyavas with 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 Oyavas with these medicines.
Tell your doctor if you use platinum- or taxane-based treatment for lung or spread breast cancer. These treatments in combination with Oyavas 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 this medicine if you are pregnant. Oyavas can harm your unborn baby as they can prevent the formation of new blood vessels. Your doctor will advise you to use contraception during treatment with Oyavas and for at least 6 months after the last dose of one of Oyavas.
If you are pregnant, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
You must not breastfeed during treatment with Oyavas and for at least 6 months after the last dose of one of Oyavas as this medicine may interfere with the growth and development of your baby.
Oyavas can impair female fertility. Contact your doctor for more information.
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.
Driving and using machines
Oyavas has not been shown to reduce your ability to drive or use tools or machines. However, drowsiness and fainting have been reported with the use of Oyavas. If you experience symptoms that affect your vision, concentration, or ability to react, do not drive or use machines until the symptoms have disappeared.
Oyavas contain sodium
This medicine contains less than 1 mmol sodium (23 mg) per vial, ie essentially ‘sodium-free’. is almost “sodium-free”.
How to use Oyavas
Dosage and dosing frequency
The dose of one Oyavas 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 Oyavas dose that is right for you. You will be treated with Oyavas 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 Oyavas can no longer prevent your tumor from growing. Your doctor will discuss this with you.
Method of administration and route of administration
Oyavas is a concentrated solution for infusion. Depending on the dose prescribed by your doctor, some or all of the contents of the Oyavas vial will be diluted with sodium chloride (saline) solution before use. A doctor or nurse will give you the diluted Oyavas 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.
Treatment with Oyavas 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 going to have surgery.
The treatment with Oyavas 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 tube-like 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 ( 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 get more Oyavas than you should
- you may develop severe migraines. If this happens, talk to a doctor, pharmacist, or nurse immediately.
If an Oyavasdos is missed
- Your doctor will decide when to take your next dose of Oyavas. You should discuss this with your doctor.
If you stop using Oyavas
Discontinuation of your treatment with Oyavas may stop the effect on tumor growth. Do not stop treatment with Oyavas 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.
The side effects listed below were seen when Oyavas was given chemotherapy. This does not necessarily mean that these side effects are caused by Oyavas.
Allergic reactions
If you get an allergic reaction, tell your doctor or healthcare professional immediately. Signs of an allergic reaction 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.
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 clot,
- feeling weak and lacking in energy,
- fatigue,
- diarrhea, nausea, vomiting, and abdominal pain.
Serious side effects, which may be common (may affect up to 1 in 10 people), include:
- holes in the intestine,
- hemorrhage, including hemorrhage 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, flaking of the 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 intestines, lungs and airways, 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 infections are in the deeper layers under the skin,
- fistula: an abnormal tube-like connection between internal organs and skin or other tissues that are not normally connected, including connections between the vagina and intestines in patients with cervical cancer.
Serious adverse reactions with an unknown frequency that have been reported (occurring in an unknown number of users) include:
- severe 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,
- 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 below for a 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,
- an enlargement and weakening of a vessel wall or a rupture in a vessel wall ( aneurysms and arterial dissections),
- 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 which may be associated with pain and inflammation in the surrounding tissue (see the list of side effects below for further recommendations),
- holes in the gallbladder (symptoms and signs may include abdominal pain, fever, and nausea/vomiting).
You should seek help as soon as possible if you get any of the following side effects.
Very common (may affect more than 1 user in 10) side effects that were not serious include:
- constipation,
- loss of appetite,
- fever,
- eye problems (including increased tear flow),
- speech disorders,
- change of taste,
- Runny nose,
- dry skin, flaking, and inflammation of the skin, change in skin color,
- weight loss,
- nosebleed.
Common (may affect up to 1 in 10 people) side effects that were not serious include:
- voice change and hoarseness.
Patients older than 65 years have an increased risk of developing the following side effects:
- blood clots in the arteries that can lead to stroke (blood clot or cerebral hemorrhage) or heart attack,
- a decrease in the number of white blood cells in the blood and a decrease in the number of platelets that help the blood clot,
- diarrhea,
- feeling sick,
- headache,
- fatigue,
- high blood pressure,
Oyavas can also cause changes in laboratory tests performed by your doctor. These include decreased white blood cell count, especially neutrophils (a type of white blood cell that helps protect against infections ) in the blood, protein in the urine, decreased blood potassium, sodium or phosphorus (a mineral), elevated 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.
How to store Olav
Keep this medicine out of the sight and reach of children.
Use before the expiry date which is stated on the label and carton after 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. Do not use Oyavas if you notice 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, monobasic sodium phosphate (monohydrate), disodium phosphate, polysorbate 20, and water for injections (see section 2 “Oyavas contains sodium”).
What the medicine looks like and the contents of the pack
Oyavas is a concentrate solution for infusion (sterile concentrate). The concentrate is a colorless to pale yellow or pale brown liquid with opalescence 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 pack of Oyavas contains one vial.
Marketing Authorization Holder and Manufacturer
Marketing Authorisation Holder
STADA Arzneimittel AG
Stadastrasse 2‑18
61118 Bad Vilbel
Germany
Manufacturer
GH GENHELIX SA
Leon Technological Park
Edifício GENHELIX
C / Julia Morros, s / n
Armunia, 24009 León, Spain
Contact the representative of the marketing authorization holder to find out more about this medicine:
STADA Nordic ApS
Tel: +45 44859999