Cizumab 400 Solution for Infusion

Cizumab contains its active substance called Bevacizumab. It is an antiangiogenic antineoplastic agent and vascular endothelial growth factor inhibitor. It is not recommended in paediatric. It is used in the treatment of colon and rectum cancer, lung cancer, breast cancer, brain tumor, Kidney cancer.

Used in the treatment of colorectal cancer, breast cancer, non-squamous non-small cell lung cancer, glioblastoma. It can be given with other chemotherapy agents like 5-fluorouracil. It is not used in children.

It is an antiangiogenic used in the treatment of different cancers like cancer or tumor of brain, breast, uterus, colon, rectum and lungs. It is used only in adults.

Colorectal Cancer

Colon cancer is also known as bowel cancer, colorectal cancer, or rectal cancer. It is a type of cancer that develops from any part of the colon or rectum. The most common Signs and symptoms are blood in the stool, a change in bowel movements, weight loss, and fatigue.

• Metastatic colorectal cancer
• Metastatic Non-squamous non-small cell lung cancer which is unresectable and locally advanced or recurrent
• Metastatic renal cell carcinoma
• Metastatic cervical cancer is persistent or recurrent
• Metastatic breast cancer
• Primary peritoneal cancer
• Epithelial ovarian and fallopian tube cancer
• Glioblastoma which is recurrent
• Hepatocellular carcinoma

Cizumab contains its active substance called Bevacizumab. Bevacizumab is an antineoplastic and an antiangiogenic agent that inhibits the function of vascular endothelial growth factor which is necessary for the supply of oxygen and nutrients to the abnormal cancerous cells. In other words, abnormal tumor cells send out VEGF into the blood that attached itself to endothelial surface VEGF thus forming new pathway for steady supply of nutrients and oxygen, the more oxygen the abnormal cell receives the better it grows and spread. Bevacizumab is a mAb that attaches itself to the circulating VEGF present in bloodstream thus inhibiting the process of angiogenesis, thus starves the abnormal cells, which in turn induces apoptosis and cell death.

Cizumab contains its active substance called Bevacizumab. Bevacizumab is an antineoplastic and an antiangiogenic agent that inhibits the function of vascular endothelial growth factor which is necessary for the supply of oxygen and nutrients to the abnormal cancerous cells. In other words, abnormal tumor cells send out VEGF into the blood that attached itself to endothelial surface VEGF thus forming a new pathway for a steady supply of nutrients and oxygen, the more oxygen the abnormal cell receives the better it grows and spread. Bevacizumab is a mAb that attaches itself to the circulating VEGF present in the bloodstream thus inhibiting the process of angiogenesis, thus starves the abnormal cells, which in turn induces apoptosis and cell death.

• if you are allergic to Cizumab or its constituents
• if you have a bleeding disorder
• if you have heart disease
• if you have a kidney disorder
• if you are going to have surgery
• if you are pregnant
• if you are breastfeeding

Common side effects that occur 1:10 patients: hypertension, peripheral neuropathy, co-infection, easy bruising and bleeding, fatigue, weakness, diarrhoea, nausea, vomiting, abdominal pain, constipation, loss of appetite, weight loss, fever, watery eyes, change in voice, change in taste perception, runny nose, proteinuria, rash, itching of the skin, muscle and joint pain

Uncommon side effects that occur 1:100 patients: thrombus formation (DVT/PE), intestinal perforation, intestinal fistula formation, heart failure, eczema and erythema of palm and soles, anaemia, increased thirst, difficulty micturition, mucosal inflammation of the intestine, full-body ache, lethargy.

• Is Cizumab safe during pregnancy?

No, taking Cizumab during pregnancy is not recommended thus inform your physician if you are pregnant or plan to get pregnant

• Can Bevacizumab be taken while breastfeeding?

No, in general, it is suggested that drugs and their metabolites can pass via breastfeeding thus it is suspected that Bevacizumab can also pass via breastfeeding.

• Does Bevacizumab cause fertility problems?

Yes, Bevacizumab decreases male and female fertility, consult your physician.

•  What type of cancer can Bevacizumab Infusion be used for?

It is mainly approved in the treatment of colon or rectal cancer. It is also used in other types of cancer includes lung, kidney, ovarian, cervical cancer

• Does a person taking Bevacizumab Infusion still need chemotherapy?

Yes, chemotherapy is needed along with this medication to work better

• How Bevacizumab Infusion works differently from chemotherapy?

Usually, this chemotherapy targets the cancer cells but this Infusion that it also prevents the growth of blood vessels which is responsible for tumours.

Alcohol

Alcohol intake may cause side effects thus caution is required. Kindly consult with your doctor.

Driving or operating machinery

Driving or operating heavy machinery may cause side effects thus caution is required. kindly consult with your doctor.

Pregnancy

It is unsafe to use during pregnancy it may cause embryo-fetal toxicity. Kindly consult with your doctor.

Breast Feeding

It is unsafe to use during breastfeeding. It may cause toxicity to the child. Kindly consult with your doctor.

Kidney Problem

It is safe to use for the patient with mild to moderate kidney problems.No dose adjustment required for severe kidney disease patients. Kindly consult with your doctor.

Liver Disease

It is safe to use in a patient with liver disease, dose adjustment is required. Kindly consult with your doctor.

Cizumab is used only in the presence of the physician.

It must be given intravenously as a slow infusion drip

It is given in separate doses – the first dose is given in approximately 90mins and the following doses are given in 30 to 60mins if there is no adverse reaction

It must be taken at the same time once a day as prescribed by your physician.

After therapy has been initiated, do not take more or less of this drug than prescribed or stop taking it without your physicians’ approval. Skipping or changing your dose without approval may cause adverse effects making the condition more difficult to treat, or worsen side effects.

If you are pregnant or breastfeeding inform your physician as they are not advisable.

• In metastatic colorectal cancer the recommended dosage
• as the first line of treatment is 5mg or 10mg per Kg given with IV 5-fluorouracil provided every 2 weeks
• 5mg/kg when given with bolus IFL
• 10mg/kg when given with FOLFOX4
• as the second line of treatment is 5mg/kg given every 2 weeks or 7.5mg/kg every 3 weeks with IV 5-fluorouracil and irinotecanoxaliplatin-based chemotherapy
• In metastatic non-squamous non-small cell lung cancer which is inoperable, either locally advanced or recurrent the recommended dosage is 15mg/kg given with carboplatin and paclitaxel every 3 weeks
• In metastatic renal cell carcinoma, the recommended dosage is 10mg/kg given with interferon alpha2a every 2 weeks
• In metastatic cervical cancer which is recurrent or persistent, the recommended dosage is 15mg/kg given with paclitaxel and cisplatin/topotecan every 3 weeks
• In an ovarian or fallopian tube or peritoneal cancer, the recommended dosage is based on the type if it is
• Platinum resistant – 10mg/kg given every 2 weeks with paclitaxel/ doxorubicin/ topotecan given weekly or 15mg/kg given every 3 weeks with topotecan
• Platinum sensitive – 15mg/kg given every 3 weeks as monotherapy until the disease regress
• In glioblastoma which is recurrent, the recommended dosage is 10mg/kg given every 2 weeks
• In metastatic breast cancer which is HER-2 negative, the usage is revoked by FDA since 2011 but off lable 1.25mg in 0.05ml solution is given once a month
• In metastatic hepatocellular carcinoma which is unresectable, the recommended dosage is 15mg/d with atezolizumab 1,200mg/kg is given every 3 weeks

Dosage modification is required in the case of gastrointestinal perforation or fistula formation, necrotizing fasciitis, haemorrhage, arterial-venous thromboembolic events, hypertensive crisis, posterior reversible encephalopathy syndrome, nephrotic syndrome, congestive heart failure and severe infusion reaction.

Cessation of dosage is required in the case of delayed wound healing, hemoptysis, uncontrolled hypertension, proteinuria >2gm/24 hrs

It is not recommended in children.

Cizumab has only been used in few patients 65 years or older. Dosage and usage are similar to adults.Kindly consult with your doctor.

• Allergice reactions - It can be mild hypersensitivity and angioedema to severe like Stevens-Johnson Syndrome and toxic epidermal necrolysis.
• Immunization with a live vaccine
• Gastrointestinal perforation or fistula formation
• Slow wound healing
• Haemorrhage – minor or major/ internal or external
• Arterial venous thrombotic events
• Heart event – hypertension to congestive heart failure
• Reversible posterior leukoencephalopathy syndrome
• Renal toxicity – proteinuria
• Infusion reaction
• Co-infection – neutropenia

• If you have any allergy
• If you have a liver problem
• If you have a kidney problem
• If you have a heart problem
• If you have a bleeding problem
• If you are pregnant or breastfeeding

It can be given intravenously with 0.9% NaCl if compatible; if not compatible can use any dextrose containing solution. Do not shake the vial before use. Store the vials at 8ºC for 8 hrs. The first infusion takes 90mins if no reaction is observed, if followed by a second infusion that takes 60mins, the rest of the following infusion takes approximately 30 mins.

Drug-Drug Interaction

Palifermin + Bevacizumab

Use alternative drug because the use of palifermin increase the toxicity of bevacizumab by other

Daunorubicin + Bevacizumab

Therapy should be administered with caution because the combination of this drug may increase the risk or developing cardiotoxicity

Dichlorphenamide + Bevacizumab

Therapy should be administered with caution because the combination of this drug decreases the serum potassium level

Siponimod + Bevacizumab

Therapy should be administered with caution because the combination of this drug increases the risk of immunosuppressive effect and also increase the risk for developing an infection

Drug-Food Interaction

Consuming grapefruit and grapefruit juice may alter the effect of bevacizumab in the blood level. Kindly avoid this while you are receiving this medicine. Kindly consult with your doctor

Drug-Disease Interaction

Bleeding:

Therapy should be administered with caution because the use of bevacizumab will increase the risk of bleeding by impairing the mechanism of wound healing and increase the complication. So, it should be avoided 28 days before surgery

Hypertension:

Therapy should be administered with caution because the use of this drug itself will increase blood pressure. Discontinue the medication if you experience hypertensive crisis and encephalopathy

Proteinuria:

Therapy should be administered with caution in patients with renal dysfunction because the use of vascular endothelial growth factor receptors increases the severity of proteinuria 

Thromboembolic disorders:

Therapy should be administered with caution in patients who are having a history of venous thromboembolism because the use of this drug can cause venous and arterial thromboembolism.

In the case of Overdosage.Kindly consult with your doctor

In case of the missed dose.Kindly consult with your doctor

Keep the medication out of children’s reach

Keep the medication away from pets

Once expired dispose immediately

Store at 8ºC

Cizumab is an antiangiogenic drug

It is used to control and treat several cancers that are metastatic and recurrent.

Do not use this medication while pregnant and lactation period.

Don’t use this medication with liver disease or renal diseases or cardiac disorders.

• Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006. Bevacizumab. [Updated 2019 Jul 20]. [Accessed 18 Feb. 2020] (online) Available from: https://www.ncbi.nlm.nih.gov/books/NBK501731/
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• [Internet]. Accessdata.fda.gov. 2018 [cited 2 April 2018]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/125085s0169lbl.pdf
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