Bonmab

Clear or slightly opalescent from colorless to light brown liquid.
Each mL of concentrate contains: Bevacizumab 25 mg corresponding to 1.4 to 16.5 mg/mL when diluted as recommended.
Each 4 mL vial contains: Bevacizumab 100 mg corresponding to 1.4 mg/mL when diluted as recommended.
Each 16 mL vial contains: Bevacizumab 400 mg corresponding to 16.5 mg/mL when diluted as recommended.
Excipients/Inactive Ingredients: The other ingredients are trehalose dihydrate, sodium phosphate, polysorbate 20 and water for injections.

Monoclonal antibodies.
Pharmacology: Mechanism of Action: Bevacizumab binds VEGF and prevents the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. The interaction of VEGF with its receptors leads to endothelial cell proliferation and new blood vessel formation in in vitro models of angiogenesis.
Administration of Bevacizumab to xenotransplant models of colon cancer in nude (athymic) mice caused reduction of microvascular growth and inhibition of metastatic disease progression.
Pharmacokinetics: Distribution: Volume of distribution: 46 mL/kg.
Elimination: Estimated half-life: Approximately 20 days.

Bevacizumab is a vascular endothelial growth factor inhibitor indicated for the treatment of: Adult patients with advanced cancer in the large bowel, in combination with fluoropyrimidine-based chemotherapy treatment.
Adult patients with metastatic breast cancer, in combination with Paclitaxel or Capecitabine chemotherapy medicinal products.
Adult patients with advanced non-small cell lung cancer, administered together with a Platinum-containing chemotherapy regimen.
Adult patients with advanced non-small cell lung cancer when cancer cells have specific mutations of a protein called epidermal growth factor receptor (EGFR), administered in combination with Erlotinib.
Adult patients with advanced kidney cancer, administered in combination with Interferon.
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 and will be administered in combination with Carboplatin and Gemcitabine.
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 and will be administered in combination with paclitaxel, or topotecan, or pegylated liposomal doxorubicin.
Adult patients with relapsed glioblastoma. When used for patients with glioblastoma, it will be administered as a single agent.
Adult patients with persistent, recurrent or metastatic cervical cancer, Bevacizumab will be administered in combination with Paclitaxel and Cisplatin or alternatively, Paclitaxel and topotecan in patients who cannot receive platinum therapy.

The dose of Bevacizumab needed depends on the 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 kilogram of a patient's body weight. Treatment with Bevacizumab will be once every 2 or 3 weeks.

The highest dose tested in humans (20 mg/kg of body weight, intravenous every 2 weeks) was associated with severe migraine in several patients.

Bevacizumab is contraindicated in patients who are allergic or hypersensitive to Bevacizumab or to any of the other ingredients of this medicine, in patients who are allergic or hypersensitive to Chinese hamster ovary (CHO) cell products or to other recombinant or humanized antibodies, and in pregnant women.

Gastrointestinal Perforations and Fistula: Discontinue for gastrointestinal perforations, tracheoesophageal fistula, grade 4 fistula, or fistula formation involving any organ.
Surgery and Wound Healing Complications: Discontinue in patients who develop wound healing complications that require medical intervention or necrotizing fasciitis.
Withhold for at least 28 days prior to elective surgery. Do not administer Bevacizumab for at least 28 days after surgery, and until the wound is fully healed.
Hemorrhage: Severe or fatal hemorrhages have occurred. Do not administer for recent hemoptysis. Discontinue for Grade 3-4 hemorrhage.
Arterial Thromboembolic Events (ATE): Discontinue for severe ATE.
Venous Thromboembolic Events (VTE): Discontinue for Grade 4 VTE.
Hypertension: Monitor blood pressure and treat hypertension. Withhold if not medically controlled; resume once controlled. Discontinue for hyper tensive crisis or hyper tensive encephalopathy.
Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue.
Renal Injury and Proteinuria: Monitor urine protein. Discontinue for nephrotic syndrome. Withhold until less than 2 grams of protein in urine.
Infusion-Related Reactions: Decrease rate for infusion-related reactions. Discontinue for severe infusion-related reactions and administer medical therapy.
Embryo-Fetal Toxicity: May cause fetal harm. Advise females of potential risk to the fetus and the need for the use of effective contraception.
Ovarian Failure: Advise females of the potential risk.
Congestive Heart Failure (CHF): Discontinue Bevacizumab in patients who develop CHF.
Driving and using other machines: Bevacizumab has not been shown to reduce the ability to drive or to use any tools or machines. However, sleeplessness and fainting have been reported with the use of Bevacizumab. If you experience symptoms that affect vision or concentration or ability to react, do not drive and use machines until symptoms disappear.

Pregnancy: Bevacizumab may cause damage to the unborn baby as it may stop the formation of new blood vessels.
Breastfeeding: Discontinue breastfeeding during the treatment with Bevacizumab and for at least 6 months after the last dose of Bevacizumab as it may interfere with the growth and development of the baby.
Fertility: Bevacizumab may impair fertility.

The side effects listed as follows are seen when Bevacizumab was given together with chemotherapy. This does not necessarily mean that these side effects were strictly caused by Bevacizumab.
Allergic reactions: Signs may include: difficulty in breathing or chest pain, redness or flushing of the skin or a rash, chills and shivering, feeling sick (nausea), or being sick (vomiting).
Severe side effects which may be very common (affects more than 1 user in 10), include: high blood pressure feeling of numbness or tingling in hands or feet, decreased number of cells in the blood, including white blood 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.
Severe side effects which may be common (affects 1 to 10 users in 100) include: 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 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 an pain in the pelvis and regions, localized 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.
Severe side effects of unknown frequency (frequency cannot be estimated from the available data), 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 as follows 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, 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 (see the paragraphs as follows the list of side effects for further recommendations), hole in the gall bladder (symptoms and signs may include abdominal pain, fever, and nausea/vomiting).
Very common (affects more than 1 user in 10) side effects, which were not severe, include: constipation, loss of appetite, fever, and 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 color, and loss of body weight.
Common (affects 1 to 10 users in 100) side effects, which were not severe include: 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, diarrhea, sickness, headache, fatigue, high blood pressure.
Bevacizumab may also cause changes in laboratory tests carried out. These include a decreased number of white cells in the blood, in particular, neutrophils (one type of white blood cell that helps protect against infections) in the blood; presence of protein in the urine; decreased blood potassium, sodium, or phosphorus (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 hemoglobin (found in red blood cells, which carry oxygen), which may be severe.

Combinations of Bevacizumab with Sunitinib maleate (prescribed for renal and gastrointestinal cancer) may cause severe side effects. Platinum or taxane-based therapies for lung or metastatic breast cancer, in combination with Bevacizumab, may increase the risk of severe side effects.

Special precautions for disposal and other handling: Bevacizumab should be prepared by a healthcare professional using aseptic technique to ensure the sterility of the prepared solution.
The necessary amount of bevacizumab should be withdrawn and diluted to the required administration volume with sodium chloride 9 mg/mL (0.9%) solution for injection. The concentration of the final bevacizumab solution should be kept within the range of 1.4 mg/mL to 16.5 mg/mL. In the majority of the occasions the necessary amount of Bevacizumab can be diluted with 0.9% sodium chloride solution for injection to a total volume of 100 mL. Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration.
Bevacizumab is for single use only, as the product contains no preservatives.
Any unused medicinal product or waste material should be disposed in accordance with local requirements.

Store at temperatures between 2-8°C. Protect from light.
Infusion solutions should be used immediately after dilution. Do not use Bevacizumab if you notice any particulate matter or discoloration prior to administration. Do not throw away any medicines via wastewater or household waste.

Targeted Cancer Therapy

L01FG01 - bevacizumab ; Belongs to the class of VEGF/VEGFR (Vascular Endothelial Growth Factor / Receptors) inhibitors. Used in the treatment of cancer.

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