AVAMAB CONCENTRATE FOR SOLUTION FOR INFUSION 400MG/16ML [SIN17102P]

Product Info

AVAMAB CONCENTRATE FOR SOLUTION FOR INFUSION 400MG/16ML

[SIN17102P]

Therapeutic Indications
Metastatic carcinoma of the colon or rectum(mCRC)
Avamab in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of patients with metastatic carcinoma of the colon or rectum.

Metastatic Breast Cancer (mBC)
Avamab in combination with paclitaxel is indicated for the treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer. Avamab in combination with capecitabine is indicated for first-line treatment of patients with HER2-negative metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate. Patients who have received taxane and anthracycline-containing regimens in the adjuvant setting within the last 12 months should be excluded from treatment with Avamab in combination with capecitabine. The effectiveness of Avamab in metastatic breast cancer (mBC) is based on an improvement in progression-free survival. Currently, no data are available that demonstrate an improvement in disease-related symptoms or increased survival with Avamab in breast cancer.

Non-Small Cell Lung Cancer (NSCLC)
Avamab, in combination with carboplatin and paclitaxel, is indicated for first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous, non-small cell lung cancer. Avamab, in combination with erlotinib, is indicated for first-line treatment of patients with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations.

Malignant Glioma (WHO Grade IV) – Glioblastoma
Avamab, as a single agent is indicated for the treatment of patients with glioblastoma after relapse or disease progression following prior therapy. The effectiveness of Avamab in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with Avamab.

Advanced and/or metastatic Renal Cell Cancer (mRCC)
Avamab in combination with interferon alfa-2a is indicated for first-line treatment of patients with advanced and/or metastatic renal cell cancer.

Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer
Avamab, in combination with carboplatin and paclitaxel is indicated for the front-line treatment of advanced (FIGO stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer. Avamab, in combination with carboplatin and gemcitabine or in combination with carboplatin and paclitaxel is indicated for the treatment of patients with recurrent, platinum-sensitive, epithelial ovarian, fallopian tube, or primary peritoneal cancer who have not received prior bevacizumab or other VEGF-targeted angiogenesis inhibitors.

Avamab in combination with paclitaxel, topotecan or pegylated liposomal doxorubicin is indicated for the treatment of patients with recurrent, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor targeted agents.

Cervical Cancer
Avamab in combination with paclitaxel and cisplatin or paclitaxel and topotecan is indicated for the treatment of persistent, recurrent, or metastatic carcinoma of the cervix.

VII. Dosage and Method of Administration
Standard Dosage
Metastatic carcinoma of the colon or rectum (mCRC)
The recommended dose of Avamab, administered as an intravenous infusion, is as follows:
First-line treatment: 5 mg/kg of body weight given once every 2 weeks or 7.5 mg/kg of body weight given once every 3 weeks
Second-line treatment : 10 mg/kg of body weight given every 2 weeks with FOLFOX-4.
5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks when used in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy regimen in patients who have progressed on a first-line Avamab- containing regimen (see section study ML18147 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
It is recommended that Avamab treatment be continued until progression of the underlying disease. Patients previously treated with Avamab can continue with Avamab treatment following first progression (see section study ML18147 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Metastatic breast cancer (mBC)
The recommended dose of Avamab, administered as an intravenous infusion, is as follows:
In combination with paclitaxel: 10 mg/kg of body weight given once every 2 weeks
In combination with capecitabine: 15 mg/kg of body weight given once every 3 weeks
It is recommended that Avamab treatment be continued until progression of the underlying disease.

Non-small cell lung cancer (NSCLC)
First-line treatment of NSCLC in combination with platinum-based chemotherapy
Avamab is administered in addition to platinum-based chemotherapy for up to 6 cycles of treatment followed by Avamab as a single agent until disease progression. The recommended dose of Avamab is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.
First-line treatment of NSCLC with EGFR activating mutations in combination with erlotinib
The recommended dose of Avamab when used in addition to erlotinib is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion. It is recommended that the treatment with Avamab in addition to erlotinib is continued until disease progression. Please refer to the full prescribing information for erlotinib for patient selection and posology.

Malignant Glioma (WHO Grade IV) – Glioblastoma
The recommended dose of Avamab is 10 mg/kg of body weight given once every 2 weeks. It is recommended that Avamab treatment be continued until progression of the underlying disease.

Advanced and/or metastatic Renal Cell Cancer (mRCC)
The recommended dose of Avamab is 10 mg/kg of body weight given once every 2 weeks as an intravenous infusion. It is recommended that Avamab treatment be continued until progression of the underlying disease.

Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer
The recommended dose of Avamab administered as an intravenous infusion is as follows.
Front-line treatment:
15 mg/kg of body weight given once every 3 weeks when administered in addition to carboplatin and paclitaxel for up to 6 cycles of treatment followed by continued use of Avamab as single agent until disease progression or for a maximum of 15 months or until unacceptable toxicity, whichever occurs earlier.

Treatment of recurrent disease:
Platinum sensitive:
15 mg/kg of body weight given once every 3 weeks when administered in combination with carboplatin and paclitaxel for 6 cycles and up to 8 cycles followed by continued use of Avamab as a single agent until disease progression. Alternatively, 15 mg/kg every 3 weeks when administrated in combination with carboplatin and gemcitabine for 6 cycles and up to 10 cycles followed by continued use of Avamab as single agent until disease progression.

Platinum resistant:
10 mg/kg body weight given once every 2 weeks when administered in combination with one of the following agents – paclitaxel, topotecan (given weekly) or pegylated liposomal doxorubicin (see section Study MO22224 for chemotherapy regimens – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Alternatively, 15 mg/kg every 3 weeks when administered in combination with topotecan given on days 1 – 5, every 3 weeks (see section Study MO22224 for chemotherapy regimen – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). It is recommended that treatment be continued until disease progression.

Cervical Cancer
The recommended dose of Avamab is 15 mg/kg every 3 weeks as an intravenous infusion administered in combination with one of the following chemotherapy regimens: paclitaxel and cisplatin, or paclitaxel and topotecan (see section study GOG-0240 for further details on the chemotherapy regimens – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). It is recommended that Avamab treatment be continued until progression of the underlying disease.

Special Dosage Instructions
Pediatric Use: The safety and efficacy of Avamab in children and adolescents (<18 years) have not been established (see section Use in Special Populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Avamab is not recommended for use in children and adolescents due to a lack of data on safety and efficacy (see also section Nonclinical Safety – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Geriatric Use: No dose adjustment is required in patients ≥ 65 years of age. However, there was an increased risk of adverse events in patients above 65 years of age (See section Elderly patients – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Renal impairment: The safety and efficacy of Avamab have not been studied in patients with renal impairment.
Hepatic impairment: The safety and efficacy of Avamab have not been studied in patients with hepatic impairment.

Method of administration
Avamab is for intravenous use. The initial dose should be delivered over 90 minutes as an intravenous infusion. If the first infusion is well tolerated, the second infusion may be administered over 60 minutes. If the 60-minute infusion is well tolerated, all subsequent infusions may be administered over 30 minutes.
It should not be administered as an intravenous push or bolus. Dose reduction for adverse reactions is not recommended. If indicated, therapy should either be permanently discontinued or temporarily suspended as described in section Special Warnings and Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information. Avamab is not formulated for intravitreal use. (see section Special Warnings and Special Precautions for Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)

Precautions to be taken before handling or administering the medicinal product
For instructions on dilution of the medicinal product before administration, see section Special precautions for disposal and other handling. Avamab infusions should not be administered or mixed with glucose solutions. It must not be mixed with other medicinal products except those mentioned in section Special precautions for disposal and other handling.

Special precautions for disposal and other handling
Do not shake the vial.
Avamab should be prepared by a healthcare professional using aseptic technique to ensure the sterility of the prepared solution. A sterile needle and syringe should be used to prepare Avamab. 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 Avamab can be diluted with sodium chloride 9 mg/mL (0.9%) solution for injection to a total volume of 100 mL.
No incompatibilities between Avamab and polyvinyl chloride or polyolefin bags or infusion sets have been observed.Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration. Avamab 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.

Diluted medicinal product
Chemical and physical in-use stability has been demonstrated for 30 days at 2°C to 8°C plus an additional 48 hours at temperature not exceeding 30°C in sodium chloride 9 mg/mL (0.9%) solution for injection. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

VI. Contraindications
Avamab is contraindicated in:

• Patients with known hypersensitivity to any components of the product

• Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanised antibodies.

• Pregnancy