Avastin (bevacizumab) concentrate for infusions 400 mg/16 ml. №1 vial

Description

Ingredients

active substance: bevacizumab;

1 vial (4 ml concentrate for solution for infusion) contains 100 mg (25 mg/ml) bevacizumab or

1 vial (16 ml of concentrate for solution for infusion) contains 400 mg (25 mg/ml) of bevacizumab;

excipients: α,α-trehalose dihydrate; sodium dihydrogen phosphate, monohydrate; anhydrous sodium hydrogen phosphate; polysorbate 20; water for injections.

Medicinal form

Concentrate for solution for infusions.

The main physical and chemical properties: clear or opalescent liquid, colorless or light brown.

Pharmacotherapeutic group

Antineoplastic agents. Monoclonal antibodies and antibody-drug conjugates. Inhibitors of vascular endothelial growth factor / vascular endothelial growth factor receptors.

Code ATH L01F G01.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

Bevacizumab is a recombinant humanized monoclonal antibody produced by DNA technology in Chinese hamster ovary cells. Bevacizumab binds to vascular endothelial growth factor (VEGF), a key factor in vasculogenesis and angiogenesis, thereby inhibiting the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells . Neutralization of the biological activity of vascular endothelial growth factor leads to a decrease in the vascularization of tumors, normalizes vessels not affected by the tumor, inhibits the formation of new vessels in the tumor, thus inhibiting tumor growth.

Administration of bevacizumab or its parent murine antibody in a xenograft model of malignant tumors in athymic mice produced active antitumor activity against human tumors, including colon, breast, brain, pancreatic, and prostate tumors. The progression of the metastatic disease was inhibited, and the permeability of the microvascular bed was also reduced.

Indications

Treatment of metastatic colorectal cancer:

• in combination with chemotherapy based on fluoropyrimidine derivatives.

Treatment of metastatic breast cancer:

• first line treatment in combination with paclitaxel;
• first-line treatment in combination with capecitabine (when treatment with other chemotherapy regimens, including taxanes or anthracyclines, is considered inappropriate). Avastin should not be prescribed to patients who have received adjuvant taxane and anthracycline regimens within the past 12 months.® in combination with capecitabine.

Treatment of unresectable advanced, metastatic or recurrent non-small cell lung cancer, excluding predominantly non-squamous cell lung cancer:

• first-line treatment in combination with chemotherapy based on platinum derivatives.

Treatment of advanced unresectable, metastatic or recurrent non-squamous non-small cell lung cancer with EGFR-activating mutations (EGFR — epidermal growth factor receptor) in adult patients:

• first-line treatment in combination with erlotinib.

Treatment of advanced and/or metastatic renal cell carcinoma in adult patients:

• the first line of therapy in combination with interferon alfa-2a.

Treatment of advanced (stages IIIB, IIIC and IV according to the classification of the International Federation of Obstetrics and Gynecology (FIGO) epithelial ovarian cancer, fallopian tube and primary peritoneal cancer in adult patients:

• first line therapy in combination with carboplatin and paclitaxel.

Treatment of the first recurrence of epithelial cancer of the ovaries, fallopian tube and primary peritoneal cancer sensitive to treatment with platinum drugs:

• in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel in adult patients who have not received prior therapy with bevacizumab or other VEGF inhibitors or agents that target the VEGF receptor.

Treatment of recurrent epithelial ovarian, fallopian tube and primary peritoneal cancer resistant to treatment with platinum drugs:

• in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin in adult patients who have received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or drugs that target the VEGF receptor.

Treatment of persistent, recurrent or metastatic cervical cancer:

• in combination with paclitaxel and cisplatin or, alternatively, paclitaxel and topotecan in adult patients who cannot receive therapy with platinum drugs.

Treatment of recurrent glioblastoma (stage IV according to WHO):

• as monotherapy after previous temozolomide therapy.

Contraindications

Hypersensitivity to bevacizumab or any other component of the medicinal product, preparations based on Chinese hamster ovary cells, or other recombinant human or humanized antibodies. Pregnancy.

Method of application and dosage

Treatment with Avastin can be carried out only under the supervision of a doctor who has experience in the use of anticancer therapy.

It is not recommended to reduce the dose of bevacizumab due to adverse reactions. If necessary, treatment with the drug Avastin (bevacizumab)must be completely or temporarily stopped.

Standard dosing regimen

Metastatic colorectal cancer

5 mg/kg or 10 mg/kg of body weight once every 2 weeks or 7.5 mg/kg or 15 mg/kg of body weight once every 3 weeks as an intravenous infusion.

Treatment with Avastin (bevacizumab) it is recommended to continue until the progression of the underlying disease or the development of unacceptable toxicity.

Metastatic breast cancer

10 mg/kg of body weight once every 2 weeks or 15 mg/kg of body weight once every 3 weeks as an intravenous infusion.

Treatment with Avastin it is recommended to continue until the progression of the underlying disease or the development of unacceptable toxicity.

Non-small cell lung cancer

First-line treatment of non-squamous non-small cell lung cancer in combination with chemotherapy based on platinum derivatives

In combination with chemotherapy based on platinum derivatives for up to 6 courses of treatment, followed by the use of the drug Avastin as monotherapy before the appearance of signs of progression of the main disease.

7.5 mg/kg or 15 mg/kg of body weight once every 3 weeks as an intravenous infusion.

Clinical benefit in patients with non-small cell lung cancer has been demonstrated at both doses — 7.5 mg/kg and 15 mg/kg.

Treatment with Avastin (bevacizumab) it is recommended to continue until the progression of the underlying disease or the development of unacceptable toxicity.

First-line treatment of non-squamous non-small cell lung cancer with EGFR-activating mutations in combination with erlotinib

EGFR mutation testing should be performed before starting combined treatment with Avastin and erlotinib. It is important to use a validated and reliable method in order to avoid false results.

The recommended dose of the drug Avastin when used in combination with erlotinib is 15 mg/kg of body weight once every 3 weeks as an intravenous infusion.

It is recommended to continue combined treatment with Avastin® and erlotinib until disease progression.

For information on the dosage and method of use of erlotinib, refer to the instructions for medical use of erlotinib.

Disseminated and/or metastatic renal cell carcinoma

10 mg/kg of body weight once every 2 weeks as an intravenous infusion.

Treatment with Avastin it is recommended to continue until the progression of the underlying disease or the development of unacceptable toxicity.

Epithelial cancer of the ovaries, fallopian tube and primary cancer of the peritoneum

The first line of treatment: in combination with carboplatin and paclitaxel for up to 6 courses of treatment, followed by the use of Avastin as monotherapy until progression of the underlying disease or for a maximum of 15 months or until the development of unacceptable toxicity, whichever occurs first.

The recommended dose of the drug Avastin is 15 mg/kg of body weight once every 3 weeks as an intravenous infusion.

Treatment of relapse of the disease:Avastin (bevacizumab) prescribed in combination with carboplatin and gemcitabine for 6 to 10 courses of treatment or in combination with carboplatin and paclitaxel for 6 to 8 courses of treatment followed by Avastin long-term as monotherapy until disease progression. The recommended dose of the drug Avastin is 15 mg/kg of body weight once every 3 weeks as an intravenous infusion.

Treatment of recurrent disease resistant to platinum drugs:Avastin (bevacizumab) used in combination with one of the following drugs: paclitaxel, topotecan (when used weekly) or pegylated liposomal doxorubicin. The recommended dose of the drug Avastin in such cases, it is 10 mg/kg of body weight once every 2 weeks as an intravenous infusion. When Avastin prescribed in combination with topotecan (on days 1–5 every 3 weeks), the recommended dose of the drug is 15 mg/kg of body weight once every 3 weeks as an intravenous infusion. The recommended duration of treatment is until disease progression or unacceptable toxicity.

Cervical cancer

Avastin® used in combination with one of the following chemotherapy regimens: paclitaxel and cisplatin or paclitaxel and topotecan.

The recommended dose of the drug Avastin® is 15 mg/kg of body weight, which is administered once every 3 weeks as an intravenous infusion.

It is recommended to continue treatment until the progression of the underlying disease or the development of unacceptable toxicity.

Recurrent glioblastoma

The recommended dose of the drug Avastin (bevacizumab) is 10 mg/kg of body weight every 2 weeks as an intravenous infusion. It is recommended to continue treatment with Avastin to the progression of the disease. A dose of 15 mg/kg every 3 weeks is not supported by the available data.

Special groups of patients

Elderly patients: elderly patients do not need dose adjustment.

Renal dysfunction:safety and efficacy of bevacizumab in patients with impaired renal function have not been studied.

Liver dysfunction:the safety and efficacy of bevacizumab in patients with impaired liver function have not been studied.

Children

The safety and efficacy of bevacizumab in children (under 18 years of age) have not been established. Available data are listed in the Adverse Reactions and Pharmacological Properties sections, but do not allow for any dosage recommendations.

There are no relevant data on the use of bevacizumab in children for the treatment of colorectal cancer, breast cancer, lung cancer, ovarian cancer, fallopian tube cancer, and primary peritoneal, cervical, and kidney cancer.

Method of introduction

The initial dose of the drug is administered over 90 minutes as an intravenous infusion. If the first infusion is well tolerated, then the second administration can be carried out within 60 minutes. If the infusion for 60 minutes is well tolerated, then all subsequent administrations can be carried out within 30 minutes.

Don’t administer the drug Avastin (bevacizumab) through intravenous jet or bolus.

Dose reduction due to adverse reactions is not recommended. In the presence of indications, therapy should be permanently canceled or temporarily suspended.

Precautions regarding the use and administration of the drug Avastin

Avastin should be prepared for use by medical specialists in aseptic conditions to ensure the sterility of the prepared solution. For the preparation of the drug Avastin a sterile needle and syringe are used for administration.

Avastin in the form of infusions cannot be administered or diluted with glucose solutions. The drug cannot be mixed with other drugs, with the exception of 0.9% sodium chloride solution for injection.

The required amount of bevacizumab should be withdrawn and diluted to the required volume for administration with 9 mg/ml (0.9%) sodium chloride solution for injection. The concentration of bevacizumab in the prepared solution should be in the range of 1.4–16.5 mg/ml. In most cases, the required amount of the drug Avastin (bevacizumab) can be diluted with 0.9% sodium chloride solution for injections to a total volume of 100 ml.

Before use, the solution must be inspected for the presence of mechanical inclusions and discoloration.

Avastin intended for single use only, as the medicine does not contain a preservative. Any unused product or waste material should be disposed of in accordance with local requirements.

No incompatibility of the drug Avastin (bevacizumab) was observed with bags made of polyvinyl chloride or polyolefin, as well as with systems for infusion.

The chemical and physical stability of the prepared solution is maintained for 48 hours at a temperature of 2 to 30 °C in 9 mg/ml (0.9%) sodium chloride solution for injection. From a microbiological point of view, the drug should be used immediately. If the drug is not used immediately, the user is responsible for the storage time and conditions of the prepared solution. The finished solution can be stored for no more than 24 hours at a temperature of 2 to 8 °C, if the dilution is carried out in controlled and validated aseptic conditions.