Avastin100 mg/4 ml

Avastin is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor (VEGF), used mainly in oncology as part of combination chemotherapy regimens. Its evidence-based indications, by strength of evidence, are:

FDA-approved / guideline-supported uses (in combination with chemotherapy or other agents, per specific approved regimens)

• Metastatic colorectal cancer - in combination with fluoropyrimidine-based chemotherapy (e.g., IFL, FOLFOX)
• Non-squamous non-small cell lung cancer (NSCLC) - first-line, in combination with carboplatin and paclitaxel (unresectable, locally advanced, recurrent, or metastatic disease)
• Recurrent glioblastoma - as a single agent in adults with progressive disease following prior therapy
• Metastatic renal cell carcinoma - in combination with interferon alfa
• Persistent, recurrent, or metastatic cervical cancer - in combination with paclitaxel and cisplatin, or paclitaxel and topotecan
• Epithelial ovarian, fallopian tube, or primary peritoneal cancer - in combination with chemotherapy (front-line, platinum-resistant recurrent, or platinum-sensitive recurrent disease), per specific approved regimens
• Hepatocellular carcinoma - in combination with atezolizumab, in patients who have not received prior systemic therapy

Off-label ophthalmic use (distinct, compounded-preparation context)

Intravitreal (into-the-eye) Avastin is widely used off-label around the world, including in Bangladesh, as a compounded/repackaged preparation for wet age-related macular degeneration, diabetic macular edema, retinal vein occlusion, and neovascular glaucoma, because it is markedly less expensive than agents formally approved for intraocular use. This ophthalmic use is not FDA-approved and requires careful aseptic repackaging by a qualified compounding facility; it should only be given under the direct supervision of an ophthalmologist experienced in intravitreal injection.

Any use of Avastin must be individualized and supervised by a qualified oncologist or ophthalmologist, as appropriate to the indication.

Each vial contains Bevacizumab, a recombinant humanized IgG1 monoclonal antibody produced in Chinese hamster ovary (CHO) mammalian cell expression system, as a sterile, preservative-free solution for intravenous infusion (commonly supplied as 100 mg/4 mL and 400 mg/16 mL single-dose vials, i.e. 25 mg/mL). Formulations may vary slightly by manufacturer; refer to the specific product label for exact excipients (e.g., trehalose dihydrate, sodium phosphate, polysorbate 20, water for injection).

Avastin is an anti-angiogenic, anti-vascular endothelial growth factor (anti-VEGF) recombinant humanized monoclonal antibody. It works by binding to and neutralizing VEGF-A, a key signaling protein that drives the growth of new blood vessels (angiogenesis) that tumors rely on for growth and spread.

It is administered exclusively by slow intravenous infusion in a hospital or specialized oncology/infusion center under medical supervision for its approved cancer indications. It is not intended for self-administration or use outside of a supervised clinical setting. A separate, off-label, compounded use exists for tiny intraocular (intravitreal) doses in ophthalmology, which follows a completely different preparation and administration pathway from the oncology formulation.

Avastin belongs to the class of anti-angiogenic agents / vascular endothelial growth factor (VEGF) inhibitors, a subclass of monoclonal antibody-based targeted anticancer therapy.

Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor (VEGF-A) in vitro and in vivo assay systems. By blocking VEGF-A from binding to its receptors (VEGFR-1 and VEGFR-2) on the surface of vascular endothelial cells, Bevacizumab inhibits endothelial cell proliferation and new blood vessel formation, thereby reducing tumor vascularization ("starving" the tumor of its blood supply) and slowing tumor growth.

Pharmacokinetics: Bevacizumab has a long elimination half-life of approximately 20 days (range 11-50 days), consistent with an IgG1 antibody, supporting dosing every 2-3 weeks. Clearance is affected by body weight, sex, and tumor burden. There is no evidence of clinically important hepatic or renal metabolism, as would be expected for a large protein molecule.

Avastin must be diluted in 0.9% Sodium Chloride Injection and administered as a slow intravenous infusion; it must never be administered as an IV push or bolus, and must never be mixed or diluted with dextrose (glucose) solutions. The first infusion is given over 90 minutes; later infusions may be given faster if well tolerated. It must be given in a facility equipped to manage infusion reactions. Do not shake the vial. Discard any unused portion, as the product contains no preservative.

For the separate off-label ophthalmic use, a trained ophthalmologist administers a small intravitreal injection under strict aseptic technique in a controlled clinical setting; this is not applicable to the intravenous oncology formulation or dosing described above.

Clinically significant interactions with Avastin include:

• Sunitinib: Concurrent or sequential use with sunitinib has been associated with severe microangiopathic hemolytic anemia (MAHA) in renal cell carcinoma patients; this combination should generally be avoided.
• Anticoagulants and antiplatelet agents (e.g., warfarin, aspirin, clopidogrel, heparin): Additive risk of bleeding, given the anti-angiogenic mechanism of Avastin; use with caution and monitor closely for hemorrhage.
• Other chemotherapeutic agents (e.g., platinum compounds, taxanes, sunitinib, other cytotoxic drugs): Avastin is used deliberately in combination with specific chemotherapy regimens per its approved indications; these combinations require monitoring for cumulative and overlapping toxicities such as myelosuppression, neuropathy, and hepatotoxicity, per the specific protocol.
• NSAIDs/other agents affecting hemostasis: May further increase bleeding risk when combined with Avastin; use cautiously.

Always inform the treating physician of all concurrent medications, including over-the-counter drugs and supplements, before starting Avastin.

Avastin carries serious, potentially fatal risks alongside common, generally manageable side effects. These differ substantially between systemic (intravenous, oncology) use and off-label ophthalmic (intravitreal) use.

Serious/boxed-warning-level risks (systemic use)

• Gastrointestinal perforation - can be fatal; presents as abdominal pain, fever, nausea, vomiting
• Severe or fatal hemorrhage - including pulmonary hemorrhage/hemoptysis, GI bleeding, CNS bleeding
• Surgical and wound-healing complications - including wound dehiscence
• Arterial and venous thromboembolic events (e.g., stroke, myocardial infarction, deep vein thrombosis, pulmonary embolism)
• Severe hypertension, hypertensive crisis, and posterior reversible encephalopathy syndrome (PRES)
• Nephrotic syndrome/severe proteinuria
• Congestive heart failure
• Ovarian failure (in premenopausal women)

Common side effects (systemic use)

Hypertension, proteinuria, fatigue/asthenia, diarrhea, abdominal pain, headache, decreased appetite, stomatitis, epistaxis (nosebleeds), altered taste, dry skin, rash, and low white blood cell counts.

Ophthalmic (intravitreal, off-label) use

Eye pain or irritation, transient increase in intraocular pressure, floaters, conjunctival hemorrhage, and rare but serious risks including endophthalmitis (intraocular infection), retinal detachment, and intraocular inflammation.

Report any severe abdominal pain, unusual bleeding, chest pain, sudden severe headache, vision changes, or signs of infection to a physician immediately.

Avastin may cause fetal harm and is associated with embryo-fetal toxicity based on its mechanism of action (inhibition of angiogenesis, essential for normal fetal development) and findings in animal reproduction studies, including congenital malformations. Avastin should not be used during pregnancy; women of childbearing potential should use effective contraception during treatment and for at least 6 months after the last dose. If pregnancy occurs during treatment, a physician must be informed immediately so that risks can be assessed.

It is not known whether Avastin is excreted in human milk; because of the potential for serious adverse effects in a nursing infant, breastfeeding is generally not recommended during treatment with Avastin and for at least 6 months after the last dose. Use only if clearly needed and only after consulting a physician, and the potential benefit must be judged to outweigh the potential risk.

These considerations relate primarily to systemic (intravenous) use; off-label ophthalmic (intravitreal) use results in much lower systemic exposure, but conservative avoidance during pregnancy and lactation is still advised unless a physician determines otherwise.

Avastin carries several serious warnings, and should only be prescribed and monitored by physicians experienced in its use.

• Gastrointestinal perforation and fistula formation: Discontinue permanently if these occur.
• Hemorrhage: Do not administer to patients with recent hemoptysis (coughing blood); discontinue for severe bleeding.
• Wound healing complications: Withhold Avastin for at least 28 days before and after elective surgery, and do not administer until surgical incisions are fully healed.
• Hypertension: Monitor blood pressure regularly; control hypertension before starting and during treatment; discontinue for hypertensive crisis.
• Proteinuria: Monitor urine protein periodically; withhold for significant proteinuria and discontinue for nephrotic syndrome.
• Arterial and venous thromboembolic events: Use with caution in patients with a prior history; discontinue for severe arterial thromboembolic events.
• Posterior reversible encephalopathy syndrome (PRES): A rare neurological disorder; discontinue if it develops.
• Congestive heart failure: Monitor for signs and symptoms, especially with prior anthracycline exposure or chest irradiation.
• Infusion-related reactions: Monitor during and after infusion; slow or stop infusion for reactions.
• For off-label ophthalmic (intravitreal) use: strict aseptic compounding and injection technique is essential to minimize the risk of endophthalmitis; only trained ophthalmologists should administer this form.

Contraindications are limited to known hypersensitivity (see Contraindications); the risks above are important precautions requiring careful clinical judgment rather than absolute contraindications.

There is limited clinical experience with overdose of Avastin; doses higher than recommended have been associated with an increased frequency of severe headache in some patients. In case of suspected overdose, seek immediate medical attention or contact emergency services/a poison control center. Management is supportive, based on the specific symptoms that develop; there is no specific antidote.

Store Avastin vials refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect vials from light by keeping them in the original carton until the time of use. Do not shake. Once diluted for infusion, use promptly; if not used immediately, the diluted solution may be stored under refrigeration for a limited time only, per the treating facility's protocol. Keep out of reach of children. This product should only be handled and stored by qualified healthcare personnel/pharmacy staff.

Pediatric use

Safety and efficacy of Avastin in pediatric patients have not been established for its approved oncology indications. Juvenile animal studies have shown effects on bone growth (physeal dysplasia); use in growing children requires specialist pediatric oncology assessment.

Geriatric use

Patients over 65 years of age treated with Avastin have shown an increased risk of arterial thromboembolic events (including stroke and heart attack) compared with younger patients. Use with caution and close monitoring in elderly patients.

Renal impairment

No formal dose adjustment has been established; use with caution and monitor renal function and proteinuria.

Hepatic impairment

Data are limited; use with caution and individualize dosing under specialist supervision.

Ophthalmic (off-label) use in special populations

Data on intravitreal use in pregnant women, children, and the elderly are limited; decisions should be individualized by the treating ophthalmologist.

Duration of treatment with Avastin is determined by the treating physician based on the specific indication and regimen, and is generally continued until disease progression, unacceptable toxicity, or completion of a defined number of cycles as specified by the chosen protocol (in some ovarian cancer regimens, for example, treatment is given for up to 22 cycles or approximately 15 months, including maintenance phase). For off-label ophthalmic use, treatment intervals and total duration are determined by the treating ophthalmologist based on disease activity and response.

Bevacizumab is classified as a monoclonal antibody, anti-angiogenic agent, and vascular endothelial growth factor (VEGF) inhibitor, within the broader category of targeted (biologic) anticancer therapies.

Bevacizumab selectively binds to and neutralizes human vascular endothelial growth factor-A (VEGF-A), preventing it from interacting with its receptors (VEGFR-1 and VEGFR-2) on vascular endothelial cells. This blocks VEGF-driven angiogenesis (new blood vessel formation), which tumors depend on to obtain nutrients and oxygen for growth and metastasis. By starving the tumor of its blood supply, Bevacizumab helps slow tumor growth when used in combination with chemotherapy or other appropriate agents. The same anti-angiogenic mechanism underlies its off-label ophthalmic use in reducing abnormal blood vessel growth and vascular leakage in retinal diseases.

Safety and efficacy of Avastin have not been established in pediatric patients for its approved oncology indications. Juvenile animal data have shown adverse effects on growing bone (physeal dysplasia), raising a theoretical concern for children and adolescents whose bones are still growing. Use of Avastin in any pediatric patient should only occur within a specialized pediatric oncology program, after careful assessment of risks and benefits, and there is no established off-label pediatric ophthalmic dosing outside of specialist centers managing severe pediatric retinal disease (e.g., retinopathy of prematurity), which remains investigational and off-label.