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 and adolescents have not been established. Avastin is not approved for use in patients under the age of 18 years. There is no relevant use of bevacizumab in the paediatric population in the granted indications. Currently available data are described in sections 4.8, 5.1, 5.2 and 5.3 but no recommendation on a posology can be made.

Avastin should not be used in children aged 3 years to less than 18 years with recurrent or progressive high-grade glioma because of efficacy concerns (see section 5.1 for results of paediatric trials).

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.

Method of administration

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.

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. Avastin 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.

4.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.

• Pregnancy (see section 4.6).

4.4 Special warnings and precautions for use
In order to improve the traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded (or stated) in the patient file.

Gastrointestinal (GI) perforations and Fistulae (see section 4.8)

Patients may be at an increased risk for the development of gastrointestinal perforation and gall bladder perforation when treated with Avastin. Intra-abdominal inflammatory process may be a risk factor for gastrointestinal perforations in patients with metastatic carcinoma of the colon or rectum, therefore, caution should be exercised when treating these patients. Prior radiation is a risk factor for GI perforation in patients treated for persistent, recurrent or metastatic cervical cancer with Avastin and all patients with GI perforation had a history of prior radiation. Therapy should be permanently discontinued in patients who develop gastrointestinal perforation.

GI-vaginal Fistulae i