Zirabev: What Is It and How Does It Work?

Zirabev is an anticancer drug with an active component, “bevacizumab-bvzr.” It is used to treat several types of cancer and belongs to the class of vascular endothelial growth factor (VEGF) inhibitors that targets VEGF proteins and blocks their activity. In cancer patients, the VEGF proteins overexpress and are typically involved in forming new blood vessels within the cancer cells to provide cells with oxygen and other nutrients needed for their growth and uncontrolled division. 

In 2019, the FDA approved Zirabev as a biosimilar version of Avastin (an already FDA-authorized biological drug) as it has the active substance, “bevacizumab.” Compared to Avastin, it offers the same effectiveness, works the same way, and shows the same side effects. 

What Is Zirabev Used To Treat?

Zirabev is used to treat six types of advanced forms of cancer with the following characteristics:

• Cancer that has spread to other areas or has not responded or been treated well previously
• Cancer that recurs (comes back) or becomes worse after previous treatment
• Cancer that cannot be removed with surgery
• Cancer that is resistant to platinum-based chemotherapy

Depending on the cancer stage and previous treatment’s failure, Zirabev can be either used as single-agent therapy or, in some cases, combined with chemotherapy agents. 

Metastatic Colorectal Cancer (mCRC)

Metastatic colorectal cancer is an advanced form of cancer that initially began in the colon or rectum but has spread to other body areas. If a patient has not previously been treated, Zirabev is used as a first-line treatment in combination with fluorouracil-based chemotherapy. 

In other cases, if the patient has been treated previously with bevacizumab (Zirabev, Avastin, or Mvasi), and their cancer did not respond well, Zirabev is then used as second-line treatment in combination with chemotherapy. 

Metastatic Renal Cell Carcinoma (mRCC)

Zirabev is used in combination with interferon-alpha to treat patients who have metastatic renal cancer (kidney cancer that has spread to other areas). 

Ovarian Cancer

Ovarian cancer represents a group of cancer that begins in the women’s ovaries and spreads to other areas, such as the fallopian tube and the peritoneum. 

Patients with this cancer are typically treated with Zirabev in combination with chemotherapy drugs (paclitaxel and carboplatin), followed by Zirabev alone. 

If a patient’s cancer is sensitive to platinum-based chemotherapy or comes back after six months, Zirabev is first used in combination with chemotherapy agents (paraplatin and either paclitaxel or gemcitabine), followed by Zirabev as a single-agent therapy. 

Metastatic Cervical Cancer

In this cancer, Zirabev is used in combination with chemotherapy agents (topotecan and paclitaxel or cisplatin and paclitaxel). 

Non-squamous, Non-small Cell Lung Cancer

Zirabev is used as a first-line treatment combined with chemotherapy agents (paclitaxel and carboplatin) in patients whose tumor is metastatic, persistent, and unresectable (the cancer cannot be removed via surgery). 

Recurrent Glioblastoma

Zirabev is used as a single agent to treat glioblastoma, an aggressive form of brain and spinal cord cancer. 

How Does Zirabev Work?

Zirabev works to slow down the growth of cancers. It contains an active component, “bevacizumab-bvzr,” which is a recombinant monoclonal (IgG1) antibody designed to recognize and bind to VEGF proteins (that typically encourages the blood vessel’s formation to provide cancer with essential nutrients to grow and divide).

Upon binding to VEGF protein, it inhibits VEGF activity. As a result, the blood vessels do not grow within the cancer cells. Due to a lack of nutrients and oxygen supply, cancer cells starve and do not progress further.

Dosage Form and Strength

Zirabev is available in a single-dose vial that is administered intravenously. The single-dose vial is available in:

• 100 mg/4 ml strength (contains 25 mg bevacizumab-bvzr/ml) 
• 400 mg/16 ml strength (contains 25 mg bevacizumab-bvzr/ml)

Zirabev Dosing Information

The doses are set according to the type of cancer being treated and the current body weight. The following are the recommended doses  according to the FDA:

For Metastatic Colorectal Cancer (mCRC)

Patients suffering from mCRC should take the following Zirabev doses in combination with intravenous fluorouracil-based chemotherapy:

• 5 mg/kg every two weeks in combination with bolus-IFL. 

• 10 mg/kg every two weeks in combination with FOLFOX4. 
• For a patient who showed progress with a bevacizumab product-containing regimen, 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks in combination with chemotherapy based on fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin. 

For Metastatic Renal Cancer

The recommended dose of Zirabev in combination with interferon-alpha is 10 mg/kg intravenously every 2 weeks. Zirabev can also be used as monotherapy at a dose of 10 mg/kg every 2 weeks. 

For Metastatic Cervical Cancer

The recommended dose is 15 mg/kg intravenously every three weeks in combination with topotecan and paclitaxel or with cisplatin and paclitaxel. 

For Ovarian Cancer

The recommended dose for ovarian cancer patients is adjusted according to their stage, treatment sensitivity, and resistance. 

• For advanced stage III/IV cancer followed by initial surgery, the dose of Zirabev in combination with paclitaxel and carboplatin is 15 mg/kg every 3 weeks for up to 6 cycles, followed by a single (Zirabev alone) dose of 15 mg/kg every 3 weeks for a total of up to 22 cycles.

• For platinum-resistant chemotherapy, the Zirabev dose in combination with topotecan, pegylated liposomal doxorubicin, or paclitaxel is 10 mg/kg every 2 weeks. In combination with just topotecan, the dose is 15 mg/kg every 3 weeks. 
• For platinum-sensitive chemotherapy, the recommended dose of Zirabev in combination with carboplatin and paclitaxel is 15 mg/kg every 3 weeks for 6 – 8 cycles, followed by a single (Zirabev alone) dose of 15 mg/kg every 3 weeks.

For Recurrent Glioblastoma

The recommended dose of Zirabev for patients with recurrent glioblastoma is 10 mg/kg intravenously every two weeks. 

For Non-squamous, Non-small Cell Lung Cancer

The recommended dose is 15 mg/kg intravenously every three weeks in combination with carboplatin and paclitaxel. 

Zirabev may affect how wounds heal. Because of this, it is recommended not to take the drug before or after surgery for 28 days until your wounds are healed completely. 

How Is Zirabev Given?

Zirabev is only given intravenously. 

Is Zirabev a Chemotherapy Drug?

No, it is not a chemotherapy drug but an immunotherapeutic drug (an antibody). However, it can be used in combination with chemotherapy drugs to get better results.

Possible Side Effects of Zirabev

Every patient reacts differently while receiving Zirabev IV infusions. Some of the common side effects they may experience during or after infusion includes:

• Headache, backache
• High blood pressure
• Inflammation of skin and nose
• Taste changes 
• Watery eyes
• Bleeding or nose bleeding
• Dry skin
• Cough, vomiting, or nausea
• Loss of appetite

Zirabev also has some severe and potentially fatal side effects which demand immediate medical attention, such as:

• Gastrointestinal perforation 
• Posterior reversible encephalopathy syndrome
• Kidney failure
• Complications in wound healing
• Infusion-related reactions causing hypertension, tremors, trouble breathing, and chest pain 
• Congestive heart failure
• Arterial thromboembolism
• Embryo-fetal toxicity
• Stroke or heart problem
• Venous thromboembolic events
• Ovarian failure

Zirabev Precautions

Zirabev therapy is not for everyone. You should consult your healthcare provider before taking Zirabev therapy if you:

• Are pregnant, as this drug causes embryo-fetal toxicity and can harm your unborn baby. 

• Are planning to become pregnant. If you’re receiving Zirabev treatment, then you must use birth control. 
• Are breastfeeding or planning to breastfeed. Since the data on Zirabev secretion in breast milk is limited, avoiding Zirabev is recommended. 
• Have a previous history of hypertension, heart failure, kidney disease, and diabetes or have undergone surgery recently.

Zirabev Cost 

The cost of Zirabev intravenous with the strength of 100 mg/4 ml (one vial) is about $613.40. For 400 mg/16 ml (one vial), the cost is about $2,453.60. The cost of this medication can vary and depends on the pharmacy you visit.