AVASTIN

Indications

• Colorectal cancer (specialist use only)
• Breast cancer (specialist use only)
• Renal cell carcinoma (specialist use only)
• Non-small cell lung cancer (specialist use only)
• Epithelial ovarian cancer (specialist use only)
• Fallopian tube cancer (specialist use only)
• Primary peritoneal cancer (specialist use only)
• Carcinoma of the cervix (specialist use only)
• Hepatocellular carcinoma (specialist use only)

Dosage

Adults: 2.5 mg/kg every 3 weeks, with adjustments as necessary based on product literature regarding dose interruption or discontinuation due to side effects.

Mechanism of action

Bevacizumab binds to human VEGF-A, preventing it from interacting with its receptors on endothelial cells. This inhibition disrupts the VEGF signaling pathway, leading to decreased vascular permeability and reduced angiogenesis, ultimately resulting in tumor starvation and reduced metastasis.

Pharmacodynamics

The pharmacodynamics of bevacizumab involve its ability to inhibit angiogenesis, which is crucial for tumor growth and metastasis. By blocking VEGF, bevacizumab decreases blood vessel formation, impacts tumor oxygenation, and alters tumor microenvironments, leading to reduced tumor size and progression. The drug's effect on the tumor vasculature can also enhance the efficacy of concurrent chemotherapy.

Pharmacokinetics

Bevacizumab is administered intravenously and has a half-life of approximately 20 days. It is distributed widely in the body, with a volume of distribution of about 3.3 L/kg. The drug undergoes non-specific catabolism, and clearance is influenced by factors such as tumor burden and the presence of antibodies against bevacizumab. Dosage adjustments may be necessary based on patient response and tolerability.

Contra-indications

• Hypersensitivity to bevacizumab or any excipients
• Active bleeding or significant bleeding disorder
• Severe uncontrolled hypertension
• Recent history of arterial thromboembolic events

Adverse effects

• Hypertension
• Proteinuria
• Gastrointestinal perforations
• Wound healing complications
• Hemorrhage
• Thromboembolic events
• Ocular disorders such as vision loss
• Fatigue
• Nausea
• Neutropenia
• Thrombocytopenia

Interactions

• May increase the risk of bleeding when used with anticoagulants
• Risk of osteonecrosis of the jaw when used concurrently with bisphosphonates
• Potentially increased risk of hypertension with other antihypertensive medications

Precautions

• History of dry eyes
• Invasive dental procedures should be avoided if possible
• Monitor blood pressure regularly during treatment
• Ophthalmic examinations are recommended at baseline and during treatment

Pregnancy

Avoid unless potential benefit outweighs risk; embryotoxic in animal studies.

Breast-feeding

Discontinue breastfeeding before starting treatment and for 3 months after last treatment.

Storage

Store in a refrigerator (2°C to 8°C). Do not freeze. Protect from light.

Formulations

• Powder for solution for infusion