Posology : מינונים

4.2     Posology and method of administration
Zirabev must be administered under the supervision of a physician experienced in the use of antineoplastic medicinal products.

Posology

Metastatic carcinoma of the colon or rectum (mCRC)
The recommended dose of Zirabev, administered as an intravenous infusion, is either 5 mg/kg or 10 mg/kg of body weight given once every 2 weeks or 7.5 mg/kg or 15 mg/kg of body weight given once every 3 weeks.

It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity.

Metastatic breast cancer (mBC)

The recommended dose of Zirabev is 10 mg/kg of body weight given once every 2 weeks or 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.

It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity.

Non-small cell lung cancer (NSCLC)

First-line treatment of non-squamous 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 7.5 mg/kg or 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.

Clinical benefit in NSCLC patients has been demonstrated with both 7.5 mg/kg and 15 mg/kg doses (see section 5.1).

It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity.

First-line treatment of non-squamous NSCLC with EGFR activating mutations in combination with erlotinib

EGFR mutation testing should be performed prior to initiation of treatment with the combination of Zirabev and erlotinib. It is important that a well-validated and robust methodology is chosen to avoid false negative or false positive determinations.

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.

For the posology and method of administration of erlotinib, please refer to the full erlotinib prescribing information.

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 treatment be continued until progression of the underlying disease or until unacceptable toxicity.

Malignant Glioma (WHO Grade IV)- Glioblastoma

The recommended dose of Zirabev administered as an intravenous infusion is 10 mg/kg of body weight given once every 2 weeks or 15 mg/kg of body weight given once every 3 weeks.

It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity.

Epithelial ovarian, fallopian tube and primary peritoneal cancer

Front-line treatment: Zirabev is 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.

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

Treatment of platinum-sensitive recurrent disease: Zirabev is administered 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. The recommended dose of Zirabev is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.

Treatment of platinum-resistant recurrent disease: Zirabev is administered in combination with one of the following agents – paclitaxel, topotecan (given weekly) or pegylated liposomal doxorubicin. The recommended dose of Zirabev is 10 mg/kg of body weight given once every 2 weeks as an intravenous infusion. When Zirabev is administered in combination with topotecan (given on days 1-5, every 3 weeks), the recommended dose of Zirabev is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion. It is recommended that treatment be continued until disease progression or unacceptable toxicity (see section 5.1, study MO22224).

Cervical cancer

Zirabev is administered in combination with one of the following chemotherapy regimens: paclitaxel and cisplatin or paclitaxel and topotecan.

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

It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity (see section 5.1).

Special populations

Elderly patients
No dose adjustment is required in the elderly.
Patients with renal impairment
The safety and efficacy have not been studied in patients with renal impairment (see section 5.2).

Patients with hepatic impairment
The safety and efficacy have not been studied in patients with hepatic impairment (see section 5.2).

Paediatric population
The safety and efficacy of bevacizumab in children aged less than 18 years old have not been established. Currently available data are described in sections 4.8, 5.1 and 5.2 but no recommendation on a posology can be made.

There is no relevant use of bevacizumab in the paediatric population in the indications for treatment of cancers of the colon, rectum, breast, lung, ovarian, fallopian tube, peritoneum, cervix and kidney.

Method of administration

Zirabev 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 4.4.

Precautions to be taken before handling or administering the medicinal product 
For instructions on dilution of the medicinal product before administration, see section 6.6. Zirabev infusions should not be administered or mixed with glucose solutions. This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.