ZIRABEV CONCENTRATE FOR SOLUTION FOR INFUSION 100 MG/4 ML
4.1 Therapeutic indications
Metastatic Carcinoma of the Colon or Rectum (mCRC)
ZIRABEV, in combination with fluoropyrimidine-based chemotherapy, is indicated for treatment of patients with metastatic carcinoma of the colon or rectum.
Metastatic Breast Cancer (mBC)
ZIRABEV, in combination with paclitaxel, is indicated for the treatment of patients who have not received chemotherapy for metastatic human epidermal growth factor receptor 2 (HER2)-negative breast cancer.
ZIRABEV, 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 ZIRABEV in combination with capecitabine.
The effectiveness of bevacizumab in metastatic breast cancer 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 bevacizumab in breast cancer.
Non-Small Cell Lung Cancer (NSCLC)
ZIRABEV, 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.
ZIRABEV, 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
ZIRABEV, as a single agent, is indicated for the treatment of patients with glioblastoma after relapse or disease progression following prior therapy.
The effectiveness of bevacizumab 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 bevacizumab.
Advanced and/or Metastatic Renal Cell Cancer (mRCC)
ZIRABEV, in combination with interferon alfa-2a, is indicated for first-line treatment of patients with advance and/or metastatic renal cell cancer.
Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer
ZIRABEV, in combination with carboplatin and paclitaxel, is indicated for the front-line treatment of advanced (International Federation of Gynecology and Obstetrics [FIGO] stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer.
ZIRABEV, 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 vascular endothelial growth factor (VEGF)-targeted angiogenesis inhibitors.
ZIRABEV, 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
ZIRABEV, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of persistent, recurrent, or metastatic carcinoma of the cervix.
4.3 Contraindications
ZIRABEV 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.
4.2 Posology and method of administration
Posology
Standard Dosage
Metastatic Carcinoma of the Colon or Rectum (mCRC)
The recommended dose of ZIRABEV, 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 5-fluorouracil/leucovorin/oxaliplatin (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 bevacizumab-containing regimen (see section 5.1 Pharmacodynamic properties – Study ML18147 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
It is recommended that ZIRABEV treatment be continued until progression of the underlying disease. Patients previously treated with ZIRABEV can continue with ZIRABEV treatment following first progression (see section 5.1 Pharmacodynamic properties – 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 ZIRABEV, 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 ZIRABEV 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
ZIRABEV is administered in addition to platinum-based chemotherapy for up to 6 cycles of treatment followed by ZIRABEV as a single agent until disease progression.
The recommended dose of ZIRABEV 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 ZIRABEV 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 ZIRABEV 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 ZIRABEV is 10 mg/kg of body weight given once every 2 weeks.
It is recommended that ZIRABEV treatment be continued until progression of the underlying disease.
Advanced and/or Metastatic Renal Cell Cancer (mRCC)
The recommended dose of ZIRABEV is 10 mg/kg of body weight given once every 2 weeks as an intravenous infusion.
It is recommended that ZIRABEV treatment be continued until progression of the underlying disease.
Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer
The recommended dose of ZIRABEV 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 ZIRABEV 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 ZIRABEV 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 ZIRABEV 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 5.1 Pharmacodynamic properties – 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 5.1 Pharmacodynamic properties – 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 ZIRABEV 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 5.1 Pharmacodynamic properties – 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 ZIRABEV treatment be continued until progression of the underlying disease.
Special Dosage Instructions
Paediatric Use
The safety and efficacy of bevacizumab in children and adolescents (<18 years) have not been established (see section 4.4 Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). ZIRABEV is not recommended for use in children and adolescents due to a lack of data on safety and efficacy (see also section 5.3 Preclinical safety data – 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 4.8 Undesirable effects – Clinical Trials – 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 bevacizumab have not been studied in patients with renal impairment.
Hepatic Impairment
The safety and efficacy of bevacizumab have not been studied in patients with hepatic impairment.
Method of Administration
Substitution by any other biological medicinal product requires the consent of the prescribing physician.
The safety and efficacy of alternating or switching between ZIRABEV and products that are biosimilar but not deemed interchangeable to ZIRABEV has not been established. Therefore, the benefit/risk of alternating or switching need to be carefully considered.
ZIRABEV should be prepared by a healthcare professional using aseptic technique. Withdraw the volume of ZIRABEV equivalent to the required dose per body weight and dilute in a total volume of 100 ml of sterile, pyrogen-free 0.9% sodium chloride. For further instructions, see sections 6.4 Special precautions for storage and 6.6 Special precautions for disposal and other handling – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.
No incompatibilities between ZIRABEV and polyvinyl chloride or polyolefin bags have been observed.
ZIRABEV infusions should not be administered or mixed with dextrose or glucose solutions (see section 6.2 Incompatibilities – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
Do not administer as an intravenous push or bolus.
The initial ZIRABEV 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.
The initial dose of ZIRABEV should be administered following chemotherapy, all subsequent doses can be given before or after chemotherapy.
ZIRABEV is not formulated for intravitreal use (see section 4.4 Special warnings and precautions for use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).
