Abevmy 100 mg/4 ml

INDICATIONS

Bevacizumab is a vascular endothelial growth factor-specific angiogenesis inhibitor indicated for the treatment of:

Metastatic colorectal cancer, with intravenous 5-fluorouracil-based chemotherapy for first-or second-line treatment.
Metastatic colorectal cancer, with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy for second-line treatment in patients who have progressed on a first-line Bevacizumab containing regimen. ... Read moreBevacizumab is a vascular endothelial growth factor-specific angiogenesis inhibitor indicated for the treatment of:

Metastatic colorectal cancer, with intravenous 5-fluorouracil-based chemotherapy for first-or second-line treatment.
Metastatic colorectal cancer, with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy for second-line treatment in patients who have progressed on a first-line Bevacizumab containing regimen.
Non-squamous non-small cell lung cancer, with carboplatin and paclitaxel for first-line treatment of unresectable, locally advanced, recurrent or metastatic disease.
Glioblastoma, as a single agent for adult patients with progressive disease following prior therapy. Effectiveness of Bevacizumab is based on improvement in objective response rate. No data available demonstrating improvement in disease-related symptoms or survival with Bevacizumab.
Metastatic renal cell carcinoma with interferon alfa.
Cervical cancer, in combination with paclitaxel and cisplatin or paclitaxel and topotecan in persistent, recurrent, or metastatic disease.
Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer that is: (1) Platinum-resistant in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan. (2) Platinum-sensitive in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine, followed by Bevacizumab as a single agent.

Limitation of Use: Bevacizumab is not indicated for adjuvant treatment of colon cancer.

PHARMACOLOGY

Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor (VEGF) in-vitro and in-vivo assay systems. Bevacizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to VEGF. Bevacizumab has an approximate molecular weight of 149 kD. Bevacizumab is produced in a mammalian cell (Chinese Hamster Ovary) expression system in a nutrient medium containing the antibiotic gentamicin. Gentamicin is not detectable in the final product. Bevacizumab is a clear to slightly opalescent, colorless to pale brown, sterile, pH 6.2 solution for intravenous infusion.

DOSAGE

Patients should continue treatment until disease progression or unacceptable toxicity.Metastatic Colorectal Cancer (mCRC): The recommended doses are 5 mg/kg or 10 mg/kg every 2 weeks when used in combination with intravenous 5-FU-based chemotherapy.

Administer 5 mg/kg when used in combination with bolus-IFL.
Administer 10 mg/kg when used in combination with FOLFOX4.
Administer 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks when used in combination with a fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based chemotherapy regimen in patients who have progressed on a first-line Bevacizumab-containing regimen.

Non-Squamous Non-Small Cell Lung Cancer: (NSNSCLC): The recommended dose is 15 mg/kg every 3 weeks in combination with carboplatin and paclitaxel.Glioblastoma: The recommended dose is 10 mg/kg every 2 weeks.Metastatic Renal Cell Carcinoma (mRCC): The recommended dose is 10 mg/kg every 2 weeks in combination with interferon alfa.Cervical Cancer: The recommended dose of Bevacizumab is 15 mg/kg every 3 weeks as an intravenous infusion administered in combination with one of the following chemotherapy regimens: paclitaxel and cisplatin, or paclitaxel and topotecan.Platinum-Resistant Recurrent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer: The recommended dose is 10mg/kg every 2 weeks in combination with one of the following intravenous chemotherapy regimens: paclitaxel, pegylated liposomal doxorubicin, or topotecan (weekly); or 15 mg/kg every 3 weeks in combination with topotecan (every 3 weeks).Platinum-Sensitive Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: The recommended dose is 15 mg/kg every 3 weeks when administered in combination with carboplatin and paclitaxel for 6 cycles and up to 8 cycles, followed by continued use of Bevacizumab 15 mg/kg every 3 weeks as a single agent until disease progression. Alternatively, 15 mg/kg every 3 weeks when administrated in combination with carboplatin and gemcitabine for 6 cycles and up to 10 cycles, followed by continued use of Bevacizumab 15 mg/kg every 3 weeks as a single agent until disease progression.

INTERACTION

A drug interaction study was performed in which irinotecan was administered as part of the FOLFIRIregimen with or without Bevacizumab. The results demonstrated no significant effect of bevacizumab on the pharmacokinetics of irinotecan or its active metabolite SN38.

SIDE EFFECTS

Most common adverse reactions (incidence >10% and at least twice the control arm rate) are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain and exfoliative dermatitis.

PREGNANCY & LACTATION

Pregnancy: Bevacizumab may cause fetal harm based on findings from animal studies and the drug’s mechanism of action.Lactation: No data are available regarding the presence of bevacizumab in human milk, the effects on the breast fed infant, or the effects on milk production. Human IgG is present in human milk, but published data suggest that breast milk antibodies do not enter the neonatal and infant circulation in substantial amounts. Because of the potential for serious adverse reactions in breastfed infants from bevacizumab, advise a nursing woman that breastfeeding is not recommended during treatment with Bevacizumab.

PRECAUTIONS & WARNINGS

Perforation or Fistula: Discontinue Bevacizumab if perforation or fistula occurs.Arterial Thromboembolic Events or ATE (e.g., myocardial infarction, cerebral infarction): Discontinue Bevacizumab for severe ATE.Venous Thromboembolic Events or VTE: Discontinue Bevacizumab for lifethreatening VTE.Hypertension: Monitor blood pressure and treat hypertension. Temporarily suspend Bevacizumab if not medically controlled. Discontinue Bevacizumab for hypertensive crisis or hypertensive encephalopathy.Posterior Reversible Encephalopathy Syndrome (PRES): Discontinue Bevacizumab.Proteinuria: Monitor urine protein. Discontinue Bevacizumab for nephrotic syndrome. Temporarily suspend Bevacizumab for moderate proteinuria.Infusion Reactions: Stop Bevacizumab for severe infusion reactions.Embryo-fetal Toxicity: Advise females of potential risk to a fetus and the need for use of effective contraception.Ovarian Failure: Advise females of the potential risk.

USE IN SPECIAL POPULATIONS

Pediatric Use: The safety, effectiveness and pharmacokinetic profile of Bevacizumab in pediatric patients have not been established. In published literature reports, cases of non-mandibular osteonecrosis have been observed in patients under the age of 18 years who have received Bevacizumab. Bevacizumab is not approved for use in patients under the age of 18 years. Antitumor activity was not observed among eight children with relapsed glioblastoma treated with bevacizumab and irinotecan. There is insufficient information to determine the safety and efficacy of Bevacizumab in children with glioblastoma. Animal Data Juvenile cynomolgus monkeys with open growth plates exhibited physeal dysplasia following 4 to 26 weeks exposure at 0.4 to 20 times the recommended human dose (based on mg/kg and exposure). The incidence and severity of physeal dysplasia were dose-related and were partially reversible upon cessation of treatment.Geriatric Use In Study: Severe adverse events that occurred at a higher incidence (≥2%) in patients aged ≥65 years as compared to younger patients were asthenia, sepsis, deep thrombophlebitis, hypertension, hypotension, myocardial infarction, congestive heart failure, diarrhea, constipation, anorexia, leukopenia, anemia, dehydration, hypokalemia, and hyponatremia. The effect of Bevacizumab on overall survival was similar in elderly patients as compared to younger patients.

THERAPEUTIC CLASS

Targeted Cancer Therapy

STORAGE CONDITIONS

Store the Bevacizumab vial in a refrigerator at 2-8°C. Keep the vial in the outer carton due to light sensitivity. Do not freeze. Keep out of reach of children.