• Bevacizumab (Avastin) is a humanized monoclonal antibody that binds and neutralizes the vascular endothelial growth factor and prevents its association with endothelial receptors, Flt-1 and KDR. Inhibition of the vascular endothelial growth factor results in the inhibition of angiogenesis and new vessel formation.
• It is thus used in a variety of conditions, primarily mitotic processes.
• Patients who have undergone surgical intervention, administration of the drug should be delayed for at least 28 days until the wound has completely healed.

Bevacizumab (Avastin) Uses:

• It is used in combination with paclitaxel and either cisplatin or topotecan to treat patients with recurrent, metastatic, or persistent cervical cancer.
• In combination with fluorouracil-based chemotherapy, it is used as a first or second-line treatment for metastatic colorectal cancer.
• In combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, it is used as a second line of treatment for metastatic colorectal cancer if the disease progresses with the first line of treatment. It is, however, not indicated for the adjuvant treatment of colon cancer.
• It is used to treat recurrent and progressive Glioblastoma as a single agent in patients with progressive disease.
• It is indicated as a first-line treatment in combination with carboplatin and paclitaxel of locally advanced, unresectable, recurrent, and metastatic non-small cell lung cancer.
• It is used in combination with interfering alpha for the treatment of metastatic renal cell carcinoma.
• It is indicated for the treatment of ovarian, fallopian tube, and primary peritoneal cancer:
  • Following initial surgical resection in the treatment of stage III epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with carboplatin and paclitaxel, followed by single-agent bevacizumab.
  • For the treatment of platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with paclitaxel, liposomal doxorubicin, or topotecan.
  • in combination with carboplatin and paclitaxel or with carboplatin and gemcitabine and then followed by single-agent bevacizumab for the treatment of platinum-sensitive recurrent epithelial, ovarian, fallopian tube, or primary peritoneal cancer.

• Off label Uses of Bevacizumab in Adults include:

  • Age-related macular degeneration
  • Metastatic Breast cancer
  • Diabetic macular edema
  • Recurrent or persistent endometrial cancer
  • Hereditary hemorrhagic telangiectasia
  • Unresectable malignant pleural mesothelioma
  • Angiosarcoma and hemangiopericytoma (Soft tissue sarcomas)

Bevacizumab Dose in Adults:

Bevacizumab dose in the treatment of Cervical cancer:

• 15 mg/kg intravenously every 3 weeks until the disease progresses or the drug can not be tolerated (in combination with paclitaxel and either cisplatin or topotecan)

Avastin dose in the treatment of colorectal cancer:

• 5 mg/kg Intravenously every 14 days (in combination with bolus-IFL) or
• 10 mg/kg every 14 days (in combination with FOLFOX4)

Avastin dose in the treatment of metastatic colorectal cancer following first-line therapy containing bevacizumab:

• 5 mg/kg Intravenous every 14 days or
• 5 mg/kg every 21 days (in combination with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based regimen)

Avastin dose in the treatment of Glioblastoma:

• 10 mg/kg Intravenous every 14 days as a single agent until disease progression or unacceptable toxicity or
• 10 mg/kg every 14 days (in combination with irinotecan) until disease progression or unacceptable toxicity.

Bevacizumab dose in the treatment of Non-small cell lung cancer as first-line therapy:

• 15 mg/kg Intravenous every 21 days (in combination with carboplatin and paclitaxel) for 6 cycles.

• Off-label combinations:

  • 15 mg/kg every 21 days (in combination with pemetrexed and carboplatin) for up to 4 cycles or
  • 5 mg/kg every 21 days (in combination with pemetrexed and cisplatin) for 4 cycles or
  • 15 mg/kg every 21 days (in combination with atezolizumab, paclitaxel, and carboplatin) for 4 to 6 cycles

• Maintenance therapy:

  • After 6 cycles of induction therapy with bevacizumab, carboplatin, and paclitaxel it is given in a dose of 15 mg/kg every 21 days as a single agent. It is continued until disease progression or unacceptable toxicity or
  • Following 4 cycles of induction therapy with bevacizumab, pemetrexed, and carboplatin, it is given in a dose of 15 mg/kg in combination with pemetrexed every 21 days until disease progression or unacceptable toxicity or
  • Following 4 cycles of induction therapy with bevacizumab, cisplatin, and pemetrexed, it is given in a dose of 5 mg/kg in combination with pemetrexed every 21 days until disease progression or unacceptable toxicity or
  • Following 4 to 6 cycles of induction therapy with atezolizumab, paclitaxel, and carboplatin, it is given in a dose of 15 mg/kg every 21 days, with or without maintenance atezolizumab until disease progression or unacceptable toxicity.

Bevacizumab dose in the treatment of Ovarian (epithelial), fallopian tube, or primary perioteneal cancer:

• 15 mg/kg intravenous every 21 days in combination with carboplatin and paclitaxel for up to 6 cycles, followed by bevacizumab 15 mg/kg every 21 days as monotherapy, for a total of up to 22 cycles or until disease progression.
• The administration of bevacizumab may be delayed until cycle 2 to reduce the risk of wound healing complications.

Bevacizumab dose in the treatment of platinum-resistant recurrent Ovarian (epithelial), fallopian tube, or primary peritoneal cancer:

• 10 mg/kg intravenous every 14 days in combination with weekly paclitaxel, every 4 weeks liposomal doxorubicin, or days 1, 8, and 15 topotecan) or
• 15 mg/kg every 21 days in combination with every 21 days topotecan.

Bevacizumab use in the treatment of platinum-sensitive recurrent Ovarian (epithelial), fallopian tube, or primary peritoneal cancer:

• 15 mg/kg Intravenous every 21 days in combination with carboplatin and gemcitabine for 6 to 10 cycles or with carboplatin and paclitaxel for 6 to 8 cycles, then continue with bevacizumab until the disease progresses or toxicity develops.

Bevacizumab dose in the treatment of metastatic Renal cell cancer:

• 10 mg/kg Intravenous every 14 days in combination with interferon alfa or
• 10 mg/kg every 14 days as monotherapy.

Bevacizumab dosage for Age-related macular degeneration:

• 25 mg (0.05 ml) intravitreal monthly for 3 months, then monthly or as needed based on an ophthalmologic assessment performed at least once a month.

Bevacizumab dosage for metastatic Breast cancer:

• 10 mg/kg Intravenous every 14 days in combination with paclitaxel.

Bevacizumab dosage for Diabetic macular edema:

• 25 mg (0.05 ml) Intravitreal initially.
• It is repeated every month depending on the response as measured by visual acuity or central subfield thickness assessment.

Avastin dose in the treatment of recurrent or persistent endometrial cancer:

• 15 mg/kg Intravenous every 21 days as monotherapy until the disease progresses or toxicity develops.

Avastin dose in the treatment of hereditary hemorrhagic telangiectasia:

• 5 mg/kg Intravenous every 14 days for 6 doses or
• 5 mg/kg every 14 days for 4 doses, followed by 5 mg/kg once a month for 4 doses.
• If required, additional doses may be administered.

Avastin dose in the treatment of unresectable malignant pleural mesothelioma:

• 15 mg/kg Intravenous every 21 days in combination with pemetrexed and cisplatin for up to 6 cycles.
• This is followed by bevacizumab maintenance therapy at 15 mg/kg once every 21 days until toxicity develops or if the disease progresses.

Avastin dose in the treatment of metastatic or locally advanced Soft tissue sarcoma and angiosarcoma:

• 15 mg/kg Intravenous every 21 days until the disease shows signs of progression or toxicity develops.

Bevacizumab dose in Children:

Avastin dosage in the treatment of Refractory solid tumor:

• Children and Adolescents:
  • 5 to 15 mg/kg/dose intravenous every 14 days in a 28-day course or
  • 5 to 10 mg/kg every 2 to 3 weeks.

Bevacizumab dosage in the treatment of recurrent or refractory medulloblastoma and Gliomas: 

• Children and Adolescents:
  • 10 mg/kg/dose Intravenous every 14 days in combination with irinotecan with or without temozolomide or
  • 15 mg/kg/dose every 21 days has also been used.

Bevacizumab dose in Renal impairment:

• Recommendations in the dose adjustment has not been provided by the manufacturer if renal impairment is present prior to the treatment.
• However, the treatment must be discontinued if the patient develops nephrotic syndrome.
• Patients who develop proteinuria that equals to or exceeds 2 gms should withhold the treatment until the proteinuria is less than 2 gms/ 24 hours.

Bevacizumab dosage in Hepatic impairment:

• The adjustment in dose has not been provided by the manufacturer in patients with liver disease.

Bevacizumab Side effects:

Common Side Effects of Bevacizumab include:

• Cardiovascular:

  • Hypertension
  • Venous Thromboembolism
  • Peripheral Edema
  • Hypotension
  • Venous Thromboembolism
  • Arterial Thrombosis

• Central Nervous System:

  • Fatigue
  • Pain
  • Headache
  • Dizziness
  • Insomnia
  • Taste Disorder
  • Peripheral Sensory Neuropathy
  • Anxiety
  • Myasthenia

• Dermatologic:

  • Alopecia
  • Exfoliative Dermatitis
  • Palmar-Plantar Erythrodysesthesia
  • Xeroderma

• Endocrine & Metabolic:

  • Ovarian Failure
  • Hyperglycemia
  • Hypomagnesemia
  • Weight Loss
  • Hyponatremia
  • Hypoalbuminemia
  • Hypocalcemia

• Gastrointestinal:

  • Nausea
  • Abdominal Pain
  • Vomiting
  • Anorexia
  • Constipation
  • Diarrhea
  • Decreased Appetite
  • Stomatitis
  • Gastrointestinal Hemorrhage
  • Dyspepsia
  • Mucosal Inflammation

• Genitourinary:

  • Proteinuria
  • Urinary Tract Infection
  • Pelvic Pain

• Hematologic & Oncologic:

  • Thrombocytopenia
  • Hemorrhage
  • Leukopenia
  • Pulmonary Hemorrhage
  • Neutropenia
  • Bruise
  • Lymphocytopenia

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Arthralgia
  • Myalgia
  • Limb Pain
  • Back Pain
  • Dysarthria

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Epistaxis
  • Upper Respiratory Tract Infection
  • Cough
  • Dyspnea
  • Allergic Rhinitis
  • Oropharyngeal Pain
  • Sinusitis
  • Nasal Sign & Symptoms
  • Rhinitis

• Miscellaneous:

  • Postoperative Wound Complication

Less Common Side Effects Of Bevacizumab Include:

• Cardiovascular:

  • Thrombosis
  • Deep Vein Thrombosis
  • Chest Pain
  • Intra-Abdominal Thrombosis
  • Syncope
  • Left Ventricular Dysfunction
  • Pulmonary Embolism

• Central Nervous System:

  • Voice Disorder

• Dermatologic:

  • Nail Disease
  • Dermal Ulcer
  • Cellulitis
  • Acne Vulgaris

• Endocrine & Metabolic:

  • Dehydration
  • Hyperkalemia
  • Hypokalemia

• Gastrointestinal:

  • Hemorrhoids
  • Xerostomia
  • Gingival Hemorrhage
  • Rectal Pain
  • Colitis
  • Intestinal Obstruction
  • Gastrointestinal Perforation
  • Gastroesophageal Reflux Disease
  • Gingivitis
  • Oral Mucosa Ulcer
  • Gastrointestinal Fistula
  • Gastritis
  • Gingival Pain

• Genitourinary:

  • Vaginal Hemorrhage

• Hematologic & Oncologic:

  • Febrile Neutropenia
  • Neutropenic Infection
  • Hemorrhage

• Hepatic:

  • Increased Serum AST

• Infection:

  • Abscess

• Neuromuscular & Skeletal:

  • Weakness
  • Neck Pain

• Ophthalmic:

  • Blurred Vision

• Otic:

  • Tinnitus
  • Deafness

• Respiratory:

  • Rhinorrhea
  • Nasal Congestion
  • Pneumonitis

• Miscellaneous:

  • Fistula
  • Infusion Related Reaction

Bevacizumab (including biosimilars of bevacizumab): Drug Interaction

Monitoring parameters while using Bevacizumab:

• Monitor for clinical and laboratory features of proteinuria and nephrotic syndrome
• Monitor blood pressure twice monthly and frequently if the patient develops hypertension.
• Monitor for allergic reactions and infusion site reactions.
• Observe for gastrointestinal perforation and fistula.
• Observe for bleeding, thromboembolism, and wound healing.
• Monitor the patient for dyspnea and worsening heart failure.

When used in patients with Age-related macular degeneration, monitor:

• intraocular pressure
• Retinal arterial perfusion
• observe for retinal detachment
• Monitor of infectious endophthalmitis

When used for the treatment of diabetic macular edema, monitor:

• Visual acuity
• central subfield thickness,
• Monitor of infectious endophthalmitis,
• cataracts, and
• retinal  detachment

When used to treat Hereditary hemorrhagic telangiectasia:

• Monitor cardiac output measurements and
• the liver radiologic response through ultrasound and hepatic CT exams before the initial treatment and at 3 and 6 months following the first dose.

How to administer Bevacizumab (Avastin)?

• The intravenous infusion should be used.
• You can continue infusions up to 30 minutes if the first one is not tolerated.
• Infusions that are not tolerated within 30 minutes can be continued for 10 minutes at 0.5 mg/kg/min.
• Hypersensitivity reactions and infusion-site reactions should be monitored closely by patients.
• The treatment should be stopped or halted in severe reactions. 
• Mild reactions can have their infusion rate reduced.
• When intravitreal drug administration takes place, it is essential to provide adequate local anesthesia. 
• It is also recommended to use topical broad-spectrum antimicrobial medications.

Bevacizumab Brand Names (International):

• Avastin

• Bevastim

• Bivastin

Bevacizumab Brand Names in Pakistan: