Generic
Bevacizumab
8 brands available in the market
At a glance
Bevacizumab is an anti-angiogenic anticancer medication used in the treatment of colorectal cancer, non-small cell lung cancer, renal cell carcinoma, glioblastoma, ovarian cancer, and cervical cancer. It prevents the formation of new blood vessels that feed tumors, thereby stopping tumor growth.
Description
Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the biological activity of human vascular endothelial growth factor (VEGF). VEGF is the key driver of vasculogenesis and angiogenesis. Bevacizumab binds to VEGF and prevents its binding to receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on endothelial cell surfaces. This neutralizes VEGF activity, reduces tumor vascularization, normalizes remaining tumor vasculature, and inhibits new tumor vessel formation, thereby inhibiting tumor growth.
Bevacizumab is typically used as a first-line option in combination with other cancer medicines. It is administered as an intravenous infusion by healthcare professionals. The first infusion is given over 90 minutes, the second over 60 minutes if tolerated, and subsequent infusions over 30 minutes if the 60-minute infusion is well tolerated.
Indications
- Metastatic colorectal cancer (first and second-line)
- Non-squamous non-small cell lung cancer
- Glioblastoma (progressive disease)
- Metastatic renal cell carcinoma
- Cervical cancer (persistent, recurrent, or metastatic)
- Platinum-resistant and platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer
Therapeutic class
Targeted Cancer Therapy
Pharmacological class
VEGF Inhibitor (Anti-angiogenic Agent)
Pharmacology
Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that inhibits the biological activity of human vascular endothelial growth factor (VEGF) in in-vitro and in-vivo assay systems. It contains human framework regions and murine complementarity-determining regions that bind to VEGF. Bevacizumab has an approximate molecular weight of 149 kD. It is produced in a mammalian cell (Chinese Hamster Ovary) expression system in a nutrient medium containing gentamicin. Gentamicin is not detectable in the final product.
Mechanism of action
Bevacizumab binds to VEGF and prevents its binding to receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on endothelial cells. By neutralizing VEGF biological activity, it reduces tumor vascularization, normalizes remaining tumor vasculature, and inhibits new tumor vessel formation, resulting in inhibition of tumor growth.
Dosage
Metastatic Colorectal Cancer (mCRC):
First-line: 5 mg/kg every 2 weeks OR 7.5 mg/kg every 3 weeks. Second-line: 10 mg/kg every 2 weeks OR 15 mg/kg every 3 weeks (with FOLFOX4) OR 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks (with fluoropyrimidine-based regimen) until disease progression.
Non-Squamous Non-Small Cell Lung Cancer (NSNSCLC): 15 mg/kg every 3 weeks (with carboplatin and paclitaxel).
Glioblastoma: 10 mg/kg every 2 weeks (single agent).
Metastatic Renal Cell Carcinoma (mRCC): 10 mg/kg every 2 weeks (with interferon alfa).
Cervical Cancer: 15 mg/kg every 3 weeks (with paclitaxel and cisplatin or paclitaxel and topotecan).
Platinum-Resistant Recurrent Ovarian Cancer: 10 mg/kg every 2 weeks OR 15 mg/kg every 3 weeks.
Platinum-Sensitive Recurrent Ovarian Cancer: 15 mg/kg every 3 weeks (with carboplatin and paclitaxel OR carboplatin and gemcitabine for 6-10 cycles, then single agent until progression).
Exudative Age-Related Macular Degeneration: 1.25 mg (0.05 mL solution) intravitreal injection monthly.
Do not initiate Bevacizumab for 28 days following major surgery (until wound is fully healed).
Administration
For healthcare professional preparation and administration only. Do not administer as IV push or bolus. First infusion over 90 minutes; second over 60 minutes if tolerated; subsequent infusions over 30 minutes if 60-minute infusion tolerated. Dilute in 100 mL of 0.9% Sodium Chloride injection.
Missed dose
If you miss a dose of Bevacizumab, please consult your doctor. Do not double the dose.
Side effects
Common (incidence >10% and at least twice control arm rate):
Epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis.
Other:
Gastrointestinal hemorrhage, minor gum bleeding, vaginal hemorrhage, neutropenia, leukopenia, anemia, dehydration, anorexia, asthenia, sepsis, deep thrombophlebitis, congestive heart failure, diarrhea, constipation, hypokalemia, hyponatremia.
Precautions & warnings
- Perforation or Fistula: Discontinue Bevacizumab if occurs.
- Arterial Thromboembolic Events (ATE): Myocardial infarction, cerebral infarction; discontinue for severe ATE.
- Venous Thromboembolic Events (VTE): Discontinue for life-threatening VTE.
- Hypertension: Monitor and treat. Temporarily suspend if not controlled; discontinue for hypertensive crisis or encephalopathy.
- Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue.
- Proteinuria: Monitor urine protein. Discontinue for nephrotic syndrome; temporarily suspend for moderate proteinuria.
- Infusion Reactions: Stop for severe infusion reactions.
- Embryo-fetal Toxicity: Advise females of potential risk and need for effective contraception.
- Ovarian Failure: Advise females of potential risk.
- Wound Healing: Inform doctor before surgery (healing ability reduced).
- Bleeding Risk: Notify doctor if unusual bleeding occurs.
- Driving: Sleepiness and dizziness may occur; avoid driving.
Contraindications
No contraindications listed in manufacturer's labeling. However, caution required in: recent hemoptysis, hypersensitivity, post-surgical complications risk.
Drug interactions
- Irinotecan/5-fluorouracil/Leucovorin: Increased incidence of epistaxis and grade 1/2 hemorrhage.
- Live Vaccines: May reduce immune response; avoid coadministration.
- Paclitaxel: Decreased paclitaxel exposure; monitor closely.
- Sunitinib: Unexpected severe toxicity (e.g., microangiopathic hemolytic anemia) reported; coadministration not recommended.
Food interactions
It is not known whether it is safe to consume alcohol with Bevacizumab. Please consult your doctor.
Use in pregnancy
May be unsafe during pregnancy. Animal studies have shown harmful effects on the developing baby. Your doctor will weigh benefits and risks before prescribing. Use effective contraception during treatment.
Pregnancy Category: D — always consult a doctor before taking during pregnancy.
Use in lactation
Probably unsafe during breastfeeding. Human IgG is present in breast milk, but published data suggest breast milk antibodies do not enter neonatal circulation substantially. However, due to potential for serious adverse reactions, breastfeeding is not recommended during Bevacizumab treatment.
Pediatric use
Safety, effectiveness, and pharmacokinetic profile in pediatric patients have not been established. Cases of non-mandibular osteonecrosis reported in patients under 18 years. Antitumor activity not observed in 8 children with relapsed glioblastoma. Juvenile animal studies showed physeal dysplasia.
Geriatric use
Elderly patients (≥65 years) had higher incidence (≥2%) of asthenia, sepsis, deep thrombophlebitis, hypertension, hypotension, myocardial infarction, congestive heart failure, diarrhea, constipation, anorexia, leukopenia, anemia, dehydration, hypokalemia, and hyponatremia. However, overall survival effect similar to younger patients.
Renal / hepatic impairment
Probably safe in kidney and liver disease (at prescribed doses). Limited data suggests dose adjustment may not be needed. Please consult your doctor.
Overdose effects
The highest dose tested in humans (20 mg/kg IV) was associated with headache in 9 out of 16 patients and severe headache in 3 out of 16 patients. Overdose may increase bleeding risk, hypertension, and proteinuria.
Storage conditions
Store the vial in a refrigerator at 2-8°C. Keep in the outer carton to protect from light. Do not freeze. Keep out of reach of children.
Chemical structure
Bevacizumab (Recombinant Monoclonal Antibody)