Bevacizumab

Approved Indications:

• Metastatic Colorectal Cancer: First- or second-line treatment in combination with chemotherapy.
• Non-Small Cell Lung Cancer (NSCLC): In combination with platinum-based chemotherapy for unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC.
• Glioblastoma: For progressive glioblastoma.
• Renal Cell Carcinoma (RCC): In combination with interferon alfa for metastatic RCC.
• Cervical Cancer: In combination with chemotherapy for persistent, recurrent, or metastatic cervical cancer.
• Ovarian Cancer: In combination with chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.
• Glioma: Newly diagnosed glioblastoma (FDA approval in some regions).
• Metastatic Breast Cancer: In combination with paclitaxel for HER2-negative metastatic breast cancer (approval varies by region).

Ophthalmic Indications (Off-label but widely accepted):

• Neovascular (Wet) Age-Related Macular Degeneration (AMD)
• Diabetic Macular Edema (DME)
• Macular Edema following Retinal Vein Occlusion

A. Intravenous (IV) Use for Oncology:

• Colorectal Cancer: 5 mg/kg IV every 2 weeks or 7.5 mg/kg IV every 3 weeks combined with chemotherapy.
• NSCLC: 15 mg/kg IV every 3 weeks with chemotherapy.
• Glioblastoma: 10 mg/kg IV every 2 weeks.
• Renal Cell Carcinoma: 10 mg/kg IV every 2 weeks with interferon alfa.
• Cervical Cancer: 15 mg/kg IV every 3 weeks with chemotherapy.
• Ovarian Cancer: 15 mg/kg IV every 3 weeks with chemotherapy.
• Breast Cancer: 10 mg/kg IV every 2 weeks or 15 mg/kg IV every 3 weeks with paclitaxel.

B. Intravitreal Injection (Ophthalmic use):

• Wet AMD: 1.25 mg injected into the vitreous cavity every 4–6 weeks.
• Diabetic Macular Edema / Retinal Vein Occlusion: Dosing similar to AMD but off-label.

Special Populations:

• No specific dose adjustment in mild/moderate renal or hepatic impairment.
• Not established in pediatric patients.
• Elderly: No dosage adjustment; monitor closely.

Bevacizumab is a recombinant humanized monoclonal antibody that selectively binds to and neutralizes vascular endothelial growth factor A (VEGF-A), a key mediator of angiogenesis. By inhibiting VEGF-A, Bevacizumab prevents binding to VEGF receptors on endothelial cells, thereby blocking new blood vessel formation (angiogenesis), reducing vascular permeability, and inhibiting tumor growth and metastasis. In ophthalmic diseases, this results in decreased pathological neovascularization and leakage within the retina.

• Absorption: IV administration results in immediate bioavailability.
• Distribution: Volume of distribution approximately 3.7–7.3 L; limited extravascular distribution.
• Metabolism: Catabolized via proteolytic enzymes into small peptides and amino acids; no hepatic metabolism via CYP450.
• Elimination: Clearance approximately 0.207 L/day; half-life about 20 days (range 11–50 days).
• Intravitreal Use: Systemic absorption is minimal; ocular half-life approximately 7–10 days.

• Pregnancy: FDA category C; animal studies show fetal harm at high doses. Use only if benefits outweigh risks; avoid during pregnancy unless essential.
• Lactation: Unknown if excreted in human milk; potential risks to infant unknown. Use caution and consider risks versus benefits.

• Primary Class: Antineoplastic Agent, Angiogenesis Inhibitor
• Subclass: Monoclonal Antibody (Anti-VEGF)

• Known hypersensitivity to Bevacizumab or any component
• Significant bleeding, active hemorrhage
• Recent surgery or non-healing wounds
• Pregnancy (unless benefits outweigh risks)
• Uncontrolled hypertension

• Bleeding: Increased risk of serious bleeding events (gastrointestinal, pulmonary, intracranial).
• GI Perforation: Cases reported, potentially fatal; risk increased with prior diverticulitis or abdominal surgery.
• Wound Healing Complications: Delay or impairment; avoid surgery during treatment.
• Hypertension: Monitor blood pressure; treat as needed.
• Thromboembolism: Increased risk of arterial thromboembolic events.
• Proteinuria: Monitor renal function and urinalysis.
• Ophthalmic Use: Endophthalmitis, retinal detachment, increased intraocular pressure.
• Immediate attention needed for signs of bleeding, thrombosis, or infusion reactions.

Common:

• Hypertension
• Fatigue
• Proteinuria
• Epistaxis
• Diarrhea
• Abdominal pain
• Nausea

Serious:

• Gastrointestinal perforation
• Serious hemorrhage
• Arterial thromboembolism
• Infusion-related reactions
• Neutropenia (with combination chemotherapy)

Ophthalmic (Intravitreal):

• Eye pain
• Conjunctival hemorrhage
• Increased intraocular pressure
• Endophthalmitis (rare but serious)

• No significant CYP450 enzyme interactions.
• Concomitant use with other agents that impair wound healing or increase bleeding risk (e.g., NSAIDs, anticoagulants) requires caution.
• Potential additive toxicity with other chemotherapeutic or targeted agents.
• Avoid live vaccines during therapy.

• Guidelines from NCCN and ESMO support Bevacizumab use in specific cancers listed above.
• FDA approval for several cancers updated with warnings emphasizing bleeding and wound healing risk.
• Ophthalmology societies recognize off-label intravitreal use as effective and cost-saving compared to approved alternatives.
• No major recent dosing changes; emphasis on patient selection and monitoring for adverse effects.

• Store vials at 2°C to 8°C (36°F to 46°F); do not freeze.
• Protect from light; keep in original carton until use.
• Do not shake.
• Use reconstituted solution promptly as per product guidelines.
• For intravitreal use, store prefilled syringes as instructed (usually refrigerated).