Stivant (Bevacizumab) for Treatment of Cancer

What is Stivant and what is it used for?

Stivant contains the active substance bevacizumab, which is a humanized monoclonal antibody. Bevacizumab binds to a protein called human vascular endothelial growth factor, which is found on the lining of blood and lymph vessels in the body. This growth factor causes blood vessels to grow within the tumours, these blood vessels provide the tumour with nutrients and oxygen. Once bevacizumab binds to VEGF, the tumour growth is prevented by blocking the growth of the blood vessels which provide the nutrients and oxygen to the tumour.

• 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 capecitabine or paclitaxel.

• Treatment of adult patients with advanced cancer in the large bowel, i.e., in the colon or rectum. Stivant will be administered in combination with chemotherapy treatment containing a fluoropyrimidine medicine.

• Treatment of adult patients with advanced NSCLC or non-small cell lung cancer when cancer cells have specific mutations of a protein called epidermal growth factor receptor. Stivant will be administered in combination with erlotinib.

• Treatment of adult patients with advanced NSCLC or non-small cell lung cancer. Stivant will be administered together with a chemotherapy regimen containing platinum.

• 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.

• Treatment of adult patients with recurrent, persistent, or metastatic cervical cancer. Stivant will be given in combination with cisplatin and paclitaxel or, alternatively, topotecan and paclitaxel in patients who cannot receive platinum therapy.

• Treatment of adult patients with fallopian tube, advanced epithelial ovarian, or primary peritoneal cancer. When used for patients with fallopian tube, advanced epithelial ovarian, or primary peritoneal cancer, it will be administered in combination with paclitaxel and carboplatin.
  • When used for those adult patients with fallopian tube, advanced epithelial ovarian, 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, Stivant will be administered in combination with carboplatin and gemcitabine or with carboplatin and paclitaxel.
  • When used for those adult patients with fallopian tube, advanced epithelial ovarian, or primary
    peritoneal cancer whose disease came back before 6 months after the last time they were
    treated with a chemotherapy regimen containing a platinum agent, Stivant will be administered
    in combination with topotecan, paclitaxel, or pegylated liposomal doxorubicin.

Do not use Stivant if

• You are allergic (hypersensitive) to bevacizumab or to any of the other ingredients of this medicine.

• You are allergic (hypersensitive) to Chinese hamster ovary (CHO) cell products or to other recombinant human or humanized antibodies.

• You are pregnant.

• You are under 18 years of age.

• Stivant may increase the risk of developing holes in the gut wall. If you have conditions causing inflammation inside the abdomen (e.g. stomach ulcers, diverticulitis, colitis associated with chemotherapy), please discuss this with your doctor.

• Stivant 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.

• Stivant 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.

• Stivant 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.

• Stivant can increase high blood pressure. If you have high blood pressure which is not well controlled with blood pressure medicines, please consult your doctor.

• Stivant also 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 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.

• Stivant can also increase the risk of developing blood clots in your veins.

• Stivant may cause bleeding, especially tumor-related bleeding. Please consult your doctor if you or your family tend to suffer from bleeding problems or if you are taking medicines to thin the blood for any reason.

• It is possible that Stivant 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 Stivant can increase the risk of bleeding in your lungs, including coughing or spitting blood. Please discuss with your doctor if you noticed this previously.

• Stivant can increase the risk of developing a weak heart. It is important that your doctor knows if you have ever received anthracyclin or had radiotherapy to your chest, or if you have heart disease.

• This medicine may cause infections and a decreased number of neutrophils.

• It is possible that Stivant can cause hypersensitivity and/ or infusion-related reactions. Please let your doctor 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 Stivant treatment. If you have headaches, vision changes, confusion, or seizure with or without high blood pressure, please contact your doctor.

• 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.

• 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 Stivant, 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 Stivant.

• If you are pregnant or planning to become pregnant. Stivant can harm your unborn baby. Make sure to use effective contraception during treatment with Stivant and for at least 6 months after the last dose of Stivant.

• If you are breastfeeding or planning to breastfeed. You must not breastfeed your baby during treatment with Stivant and for at least 6 months after the last dose of Stivant as it can pass into your breast milk.

The dosage of Stivant 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 Stivant that is right for you. You will be treated with Stivant once every 2 or 3 weeks. The number of infusions that you receive will depend on how well you respond to the treatment; you should continue to receive this medicine until Stivant fails to stop your tumour growing.

It is available in 80mg/4ml concentrate for solution for infusion, 200mg/10ml concentrate for solution for
infusion, and 400mg/20ml concentrate for solution for infusion

Stivant is a concentrated solution for infusion. Depending on the dose prescribed for you, some or all of the contents of the Stivant vial will be diluted with sodium chloride solution before use. A doctor will give you this diluted Stivant 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.

• 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

• severe high blood pressure which cannot be controlled by blood pressure medicines, or a sudden severe rise in blood pressure,

• a hole in your gut wall,

• presence of protein in your urine accompanied by swelling of your body,

• 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,

• a blood clot in your arteries,

• serious infections of the skin or deeper layers under the skin,

• any severe bleeding.

• a blood clot in the blood vessels of your lungs,

If too much Stivant is given, you may develop a severe migraine. If this happens you should talk to your doctor immediately.

• Allergic reactions: If you have an allergic reaction, tell your doctor 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, chills, shivering, feeling sick (nausea), or being sick (vomiting). You should seek help immediately if you suffer from any of the below-mentioned side effects.

• 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,

• Diarrhea, nausea, vomiting, and abdominal pain.

• Perforation of the gut,

• Bleeding, including bleeding in the lungs in patients with non-small cell lung cancer, bloody discharge after cough

• 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,

• Heart failure,

• Blocking of the veins of the legs by a blood clot,

• 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

• Inflammation of the moist lining of mouth and gut, lungs and air passages, reproductive, and urinary tracts,

• Dry mouth in combination with thirst and/or reduced or darkened urine,

• 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,

• Localized pus collection,

• Infection, and in particular infection in the blood or bladder,

• Reduced blood supply to the brain or stroke,

• Nose bleed,

• Sleepiness,

• An increase in heart rate (pulse),

• Blockage in the gut or bowel,

• Abnormal urine test (protein in the urine),

• 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 the gut in patients with cervical cancer.

• Shortness of breath or low levels of oxygen in the blood,

• Infections of the skin or deeper layers under the skin,

• 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),

• 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,

• A brain condition with symptoms including seizures (fits), headache, confusion, and changes in vision (Posterior Reversible Encephalopathy Syndrome or PRES),

• A negative effect on a woman’s ability to have children

• Symptoms that suggest changes in normal brain function (headaches, vision changes, confusion, or seizures), and high blood pressure,

• 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 stomach or intestines,

• A hole in the cartilage wall separating the nostrils of the nose,

• 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 (feces) or blood in your vomit),

• Hole in the gall bladder (symptoms and signs may include abdominal pain, fever, and nausea/ vomiting).

• 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,

• Bleeding from the lower part of the large bowel,

• 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, inflammation of the skin, and change in skin colour,

• Nose bleeds.

• Loss of body weight,

• Voice changes and hoarseness.

• Reduction in the number of white cells in the blood and cells that help the blood clot,

• Blood clots in the arteries may lead to a stroke or a heart attack,

• Diarrhea,

• Headache,

• Sickness,

• Fatigue,

• High blood pressure

• Presence of protein in the urine,

• Decreased blood potassium, sodium, or phosphorous (a mineral),

• 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,

• 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 hemoglobin (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.

• Keep this medicine out of reach of children.

• Store in a refrigerator (2-8˚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 Stivant if you notice any particulate matter or discoloration prior to administration.

The active substance is Bevacizumab.

The other ingredients are Trehalose dihydrate, Sodium Phosphate, Polysorbate 20, and Water for Injections.