Avastin (Bevacizumab) is a monoclonal antibody that inhibits angiogenesis by binding to vascular endothelial growth factor (VEGF). It is used in the treatment of various cancers including colorectal, cervical, and ovarian cancers.
Bevacizumab (Avastin) Uses:
|
Condition |
Drug(s) |
Treatment |
|
Cervical cancer |
Avastin (bevacizumab), Mvasi (bevacizumabawwb; biosimilar) |
Used in the treatment of persistent, recurrent, and metastatic cervical cancer, in combination with paclitaxel and either cisplatin or topotecan |
|
Colorectal cancer |
Avastin, Mvasi |
|
|
Glioblastoma |
Avastin |
Used in the management of recurrent glioblastoma |
|
Glioblastoma |
Mvasi |
Used in the treatment of glioblastoma as a single agent in patients with advanced disease |
|
Non-small cell lung cancer |
Avastin, Mvasi |
First-line treatment of surgically non-resectable, locally advanced, recurrent, or metastatic nonsquamous non-small cell lung cancer (NSCLC) in combination with carboplatin and paclitaxel |
|
Ovarian cancer |
Avastin |
|
|
Renal cell carcinoma |
Avastin, Mvasi |
Used in the management of metastatic renal cell carcinoma (RCC) in combination with interferon alfa |
|
Off-label use |
Bevacizumab |
|
Bevacizumab (Avastin) Dose in Adults
It is not administered until at least 28 days after surgery and the wound is fully healed.
Use in the treatment of Cervical cancer, persistent/ recurrent/ metastatic (Avastin [bevacizumab], Mvasi [bevacizumabawwb; biosimilar]):
- It is given as 15 mg/kg intravenous every 3 weeks in combination with paclitaxel and either cisplatin or topotecan, until disease progression has stopped or unacceptable toxicity.
Bevacizumab Use in the treatment of metastatic colorectal cancer, in combination with fluorouracil-based chemotherapy (Avastin, Mvasi):
- It is given as 5 mg/kg intravenously every 2 weeks (in combination with bolus-IFL) OR
- 10 mg/kg biweekly (in combination with FOLFOX4)
Bevacizumab Use in the treatment of metastatic colorectal cancer, following first-line therapy containing bevacizumab (Avastin, Mvasi):
- It is given as 5 mg/kg Intravenous biweekly OR
- 5 mg/kg every 3 weeks in combination with the fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin based regimen.
Bevacizumab Use in the treatment of Glioblastoma, recurrent, or progressive (Avastin, Mvasi):
- it is given as 10 mg/kg intravenous biweekly as a single agent until disease progression has stopped or unacceptable toxicity OR
- as an off-label combination of 10 mg/kg every 2 weeks along with irinotecan. until disease progression has stopped or unacceptable toxicity.
Bevacizumab Use in the treatment of Non-small cell lung cancer (nonsquamous cell histology), first-line therapy (Avastin, Mvasi):
- It is given as 15 mg/kg intravenously every 3 weeks in combination with carboplatin and paclitaxel for 6 cycles.
- Off-label combinations:
- 15 mg/kg every 3 weeks in combination with pemetrexed and carboplatin, for up to 4 cycles OR
- 5 mg/kg every 3 weeks in combination with pemetrexed and cisplatin for 4 cycles OR
- 15 mg/kg every 3 weeks in combination with atezolizumab, paclitaxel, and carboplatin for 4 to 6 cycles.
- Maintenance therapy:
- It is administered as 15 mg/kg every 3 weeks as a single agent after 6 cycles of induction therapy with bevacizumab, carboplatin, and paclitaxel.
- Then continue maintenance therapy until disease progression has stopped or unacceptable toxicity OR
- 15 mg/kg in combination with pemetrexed every 3 weeks after 4 cycles of induction therapy with bevacizumab, pemetrexed, and carboplatin. Then continue until disease progression has stopped or unacceptable toxicity OR
- 5 mg/kg in combination with pemetrexed every 3 weeks after 4 cycles of induction therapy with bevacizumab, cisplatin, and pemetrexed. Then continue until disease progression has stopped or unacceptable toxicity OR
- 15 mg/kg every 3 weeks, with or without maintenance atezolizumab after 4 to 6 cycles of induction therapy with atezolizumab, paclitaxel and carboplatin. Then continue until disease progression has stopped or unacceptable toxicity.
Bevacizumab Use in the treatment of Ovarian (epithelial), fallopian tube, or primary peritoneal cancer (stage III or Intravenous disease following initial surgical resection) (Avastin):
- It is given as 15 mg/kg Intravenous every 3 weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by bevacizumab 15 mg/kg every 3 weeks monotherapy, for a total of up to 22 cycles or until disease progression, whichever occurs earlier.
- It might delay bevacizumab to begin at cycle 2 to reduce the risk of wound healing complications.
Bevacizumab Use in the treatment of Ovarian (epithelial), fallopian tube, or primary peritoneal cancer (platinum-resistant recurrent) (Avastin):
- It is administered as 10 mg/kg intravenously biweekly in combination with weekly paclitaxel, every 4 weeks liposomal doxorubicin, or days 1, 8, and 15 topotecan OR
- 15 mg/kg every 3 weeks in combination with every 3-week topotecan.
Bevacizumab Use in the treatment of Ovarian (epithelial), fallopian tube, or primary peritoneal cancer (platinum-sensitive recurrent) (Avastin):
- Its dose is 15 mg/kg intravenously every 3 weeks 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 as monotherapy until disease progression has stopped or unacceptable toxicity has occurred.
Bevacizumab Use in the treatment of metastatic Renal cell cancer (Avastin, Mvasi):
- it is given as 10 mg/kg intravenously biweekly in combination with interferon alfa or
- as off-label dosing, 10 mg/kg every 2 weeks as monotherapy.
Bevacizumab (Avastin) Off label use in the treatment of Age-related macular degeneration:
- it is given as 25 mg Intravitreal (0.05 mL) monthly for 3 months, then can be given monthly or as needed based on monthly ophthalmologic assessment.
Bevacizumab (Avastin) Off label use in the treatment of metastatic breast cancer:
- It is administered as 10 mg/kg intravenously biweekly in combination with paclitaxel.
Bevacizumab (Avastin) Off label use in the treatment of diabetic macular edema:
- It is given as 25 mg Intravitreal (0.05 mL) initially then repeat the dose every 4 weeks depending on ophthalmologic response i.e visual acuity or central subfield thickness assessment.
- Institutional guidelines must be sought.
Bevacizumab (Avastin) Off label use in the treatment of recurrent or persistent endometrial cancer:
- It is given as 15 mg/kg Intravenous every 3 weeks as monotherapy until disease progression has stopped or unacceptable toxicity has occurred.
Bevacizumab (Avastin) Off label use in the treatment of Hereditary hemorrhagic telangiectasia:
- It is given as 5 mg/kg intravenously biweekly for 6 doses OR
- 5 mg/kg every 2 weeks for 4 doses, followed by 5 mg/kg once a month for 4 doses. The additional dosescan be administered if the response is not up to the mark.
Bevacizumab (Avastin) Off label use in the treatment of unresectable malignant pleural mesothelioma:
- It is given as 15 mg/kg intravenously every 3 weeks in combination with pemetrexed and cisplatin for up to 6 cycles, followed by bevacizumab maintenance therapy at 15 mg/kg once every 3 weeks until disease progression has stopped or unacceptable toxicity has occurred.
Bevacizumab (Avastin) Off label use in the treatment of metastatic or locally advanced soft tissue sarcoma, angiosarcoma:
- It is given as 15 mg/kg intravenously every 3 weeks until disease progression has stopped or unacceptable toxicity has occurred.
Bevacizumab (Avastin) Dose in Children
Please be aware that it is important to follow specific treatment protocols for each individual case. It is also recommended to consult the appropriate dosing details for combination treatments.
Clinical trials involving pediatric patients used Avastin 25 mg/mL vials for bevacizumab injections. Mvasi, a biosimilar of Avastin, is also available, but there is limited data on its use in pediatric oncology patients.
Bevacizumab (Avastin) Use in the treatment of Refractory solid tumor:
- Children and Adolescents:
- It is used as 5 to 15 mg/kg/dose intravenously biweekly in a 28-day course OR
- 5 to 10 mg/kg every 2 to 3 weeks.
Bevacizumab (Avastin) Use in the treatment of recurrent or refractory primary CNS tumor (high or low-grade gliomas, medulloblastoma):
- It is given as 10 mg/kg/dose intravenously biweekly OR days 1 and 15 of each 28-day cycle. It is mostly used in combination with irinotecan with or without temozolomide OR
- 15 mg/kg/dose every 3 weeks has also been used.
- When treating high-grade glioma, patients with the contrast-enhancing disease showed greater response or remained stable, while patients with non-contrast-enhancing disease had disease progression. Some studies have observed only minimal efficacy in patients with high-grade glioma.
Bevacizumab Dosing adjustment for toxicity:
The dosing adjustments provided are based on clinical experience with adult oncology patients. However, there is limited information available for pediatric patients, so local guidelines should be followed if available.
For adult patients receiving intravenous administration, there are no recommended dosage reductions. However, the drug should be withheld in cases of severe infusion reactions for at least 4 weeks before and after elective surgery.
In cases of moderate to severe proteinuria or severe hypertension that is not controlled with medical management, treatment should be withheld if proteinuria exceeds 2 g/24 hours or if hypertension is severe.
Permanent withholding of the drug is recommended in cases where patients develop:
- wound dehiscence and wound healing complications requiring surgical intervention,
- necrotizing fasciitis,
- fistula (gastrointestinal or non-gastrointestinal),
- gastrointestinal perforation,
- intra-abdominal abscess,
- hypertensive crisis or hypertensive encephalopathy,
- serious bleeding/hemorrhage,
- the severe arterial thromboembolic event,
- life-threatening (grade 4) venous thromboembolic events (including pulmonary embolism),
- nephrotic syndrome, or
- PRES (Posterior Reversible Encephalopathy Syndrome).
Bevacizumab (Avastin) Pregnancy Category: C
Studies on animal reproduction have shown that bevacizumab can cause adverse outcomes in pregnant women. Information about its effects during pregnancy is incomplete. Women of reproductive potential should use effective contraception for at least 6 months after their last bevacizumab dose. Bevacizumab may increase the risk of ovarian failure, impaired fertility, and ovarian cancer, but long-term effects on fertility are unknown.
The presence of bevacizumab in breast milk has not been confirmed, but breast milk has been shown to contain immunoglobulins, so it's possible that bevacizumab might be present as well. Breastfeeding is not recommended during treatment or for six months after the last bevacizumab dose.
Bevacizumab (Avastin) Dose in Kidney Disease:
- Renal impairment prior to treatment:
- No specific dose adjustments are required in renal impairment.
- Renal toxicity during treatment:
- Nephrotic syndrome:
- Withhold bevacizumab.
- Proteinuria of more than 2 g/24 hours in the absence of nephrotic syndrome: then withhold bevacizumab until proteinuria is less than 2 g/24 hours.
- Nephrotic syndrome:
Bevacizumab (Avastin) Dose in Liver disease:
- No specific dose adjustments are mentioned in the literature for liver impairment.
Percentages reported as monotherapy and as part of combination chemotherapy regimens.
Common Side Effects of Bevacizumab (Avastin):
- 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 (Avastin):
- 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
- Gastro-esophageal 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
Contraindications to Bevacizumab (Avastin):
In the US labeling, there are no contraindications for bevacizumab.
However, in Canadian labeling, it is considered a contraindication if someone has hypersensitivity to any component of bevacizumab.
Hypersensitivity reactions to Chinese Hamster Ovarian Cell Products, other recombinant human/humanized antibodies, or untreated CNS Metastatic Disease are also listed as contraindications.
Warnings and precautions
Perforation of the gastrointestinal tract/ fistula [US Boxed Warning]:
- Bevacizumab products can cause fatal gastrointestinal (GI) perforation in patients, with a risk ranging from 0.3% to 3%. If a patient has GI perforation, the use of bevacizumab products should be stopped.
- Previous pelvic radiation increases the risk of GI perforation. Most cases of GI perforation were diagnosed within 50 days after the initial bevacizumab treatment and may be related to fistula, intraabdominal abscess, or diverting ostomy.
- Patients receiving bevacizumab have a higher rate of serious fistulae, such as tracheoesophageal and bronchopleural, biliary, compared to those receiving chemotherapy.
- The highest incidence was seen in patients with cervical carcinoma. The majority of fistulae develop within six months of the first bevacizumab dose.
- Patients with gastrointestinal vaginal fistula may also develop bowel obstruction, requiring surgical intervention and diverting ostomy. Patients with ovarian cancer who show evidence of rectosigmoid involvement, such as pelvic examinations or bowel involvement on CT scan, or clinical signs of bowel obstruction, should not use bevacizumab.
- Patients who experience gastrointestinal perforation, tracheoesophageal or grade 4 fistulas, or fistula formations involving any internal organ, should have bevacizumab withheld.
Heart Failure:
- According to the American Heart Association's scientific statement, bevacizumab can cause irreversible damage to the heart muscle or worsen existing heart problems.
- Combining bevacizumab with chemotherapy that contains anthracycline is not recommended. Patients who received bevacizumab along with chemotherapy had a higher incidence of left ventricular dysfunction compared to those who received chemotherapy alone (1% vs. 0.6%).
- Patients who had previously received anthracycline therapy before chemotherapy were more likely to develop heart disease compared to patients who received chemotherapy without anthracycline (4% vs. 0.6%).
- Patients receiving bevacizumab in combination with anthracycline were more likely to experience heart failure or reductions in left ventricular ejection fraction (LVEF) compared to patients who received anthracycline alone.
- Patients receiving bevacizumab in combination with chemotherapy also had a higher proportion of patients with significant declines in LVEF (20% or more) or moderate declines (10% to 50%) from baseline compared to patients receiving chemotherapy alone (5% vs. 5%).
- Most cases of heart failure occurred within 1 to 6 months after the first dose of bevacizumab, and approximately one-third (33%) of patients had their heart failure resolved. Patients with heart failure should not receive bevacizumab products.
Hemorrhage [US Boxed Warning]:
- Patients who have received bevacizumab products are at risk of severe or fatal bleeding. Patients who have hemoptysis (coughing up blood) of 5 mL or more should not receive bevacizumab products.
- Patients who experience grade 3-4 bleeding should immediately stop using bevacizumab products. Nearly one-third of patients who received bevacizumab in combination with chemotherapy for nonsmall cell lung cancer (NSCLC) with squamous cell histology (which is not FDA-approved indication), and a small number of NSCLC with nonsquamous histology, have experienced serious or fatal pulmonary bleeding.
- Patients who received chemotherapy alone did not experience any such cases. Sometimes, minor bleeding events (including grade 1 nosebleeds) can occur.
Hypertension:
- Bevacizumab may worsen preexisting hypertension or cause new cases of hypertension. Bevacizumab products increase the risk of severe hypertension. Managing hypertension with antihypertensive therapy can be helpful.
- If you develop hypertension due to bevacizumab, it is important to regularly monitor your blood pressure every 2 to 3 weeks. Patients with severe hypertension that is not controlled with medical management should discontinue bevacizumab.
- Bevacizumab may be resumed after blood pressure is adequately controlled. Patients who experience a hypertensive crisis or hypertensive encephalopathy should stop taking bevacizumab.
Infusion reactions:
- Infusion reactions with bevacizumab are rare, but they can happen after the first infusion. These reactions may include symptoms such as hypertension, hypertensive crises (with neurologic symptoms), wheezing, oxygen desaturation, hypersensitivity (grade 3), chest pain, rigors, and headaches. Severe reactions are not common, but they can occur.
- Mild or insignificant infusion reactions can be treated by reducing the infusion rate. If there are clinically serious infusion reactions, infusions should be stopped. After the resolution of the reactions, it may be possible to resume infusions at a slower pace.
- For severe reactions to bevacizumab, it is important to stop taking it and seek appropriate medical treatment, such as epinephrine or corticosteroids, intravenous antihistamines (IVAs), bronchodilators, and oxygen supplementation
Mortality:
- Combining chemotherapy with biological therapy or bevacizumab can raise the risk of treatment-related death.
- A meta-analysis of 16 trials that used bevacizumab to treat various cancers, such as breast cancer, colorectal cancer, non-small cell lung cancer (NSCLC), and prostate cancer, showed a higher risk of fatal adverse reactions compared to chemotherapy alone.
Necrotizing fasciitis:
- Some patients who have received bevacizumab have experienced necrotizing fasciitis, including cases that resulted in fatalities.
- This is typically associated with complications in wound healing, gastrointestinal perforation, or fistula formation. Patients diagnosed with necrotizing fasciitis should discontinue the use of bevacizumab.
Ocular adverse events:
- Severe eye infections and vision impairments have been reported when bevacizumab is used off-label as an intravitreal treatment.
Osteonecrosis in the jaw (ONJ):
- A position paper from the American Association of Maxillofacial Surgery (AAOMS) states that medication-related osteonecrosis of the jaw (MRONJ) has been linked to bisphosphonates, other antiresorptive drugs (such as denosumab), as well as antiangiogenic agents like sunitinib and bevacizumab, which are used in the treatment of osteoporosis.
- Combining antiresorptive and antiangiogenic agents increases the risk of MRONJ. MRONJ can also be caused by concurrent steroid use, preexisting inflammatory conditions, and dental surgeries such as tooth removal or dental implants.
- According to AAOMS, antiangiogenic agents should only be used when medically necessary, and antiangiogenesis therapy should be avoided until the extraction site has healed or mucosalized.
- After initiating antiangiogenic treatment for oncologic diseases, procedures that directly affect the bone and dental implant placement should be avoided. Consultation with an oral surgeon is recommended for patients who develop MRONJ due to therapy.
- There have been reported cases of non-mandibular MRONJ in pediatric patients who received bevacizumab, which is not approved for use in pediatric patients.
Failure of the ovarian system:
- In premenopausal women with solid tumors who received adjuvant chemotherapy, the incidence of ovarian dysfunction was 34% when bevacizumab was combined with chemotherapy, compared to 2% with chemotherapy alone.
- Only a small percentage (around one-fifth or less) of females who received bevacizumab showed signs of recovery of ovarian function. The long-term effects of bevacizumab on fertility have not been studied.
- It is important to inform females of reproductive potential about the possibility of premature ovarian failure before initiating bevacizumab treatment.
The posterior reversible syndrome of encephalopathy:
- There have been cases where patients experienced a condition called posterior reversible encephalopathy syndrome (PRES) during treatment. Symptoms of PRES may include headaches, seizures, confusion, lethargy, and blindness.
- These symptoms can occur anytime between 16 hours and 1 year after treatment. PRES may also be linked to mild-to-severe hypertension. Diagnosis of PRES requires an MRI.
- Patients diagnosed with PRES should not receive bevacizumab products. Symptom relief usually occurs within a few days of discontinuing treatment, but there may still be lasting effects on the nervous system. It is unknown whether reinitiating bevacizumab treatment after PRES is safe.
Nephrotic syndrome/proteinuria:
- Bevacizumab products have been linked to an increase in the severity and frequency of proteinuria (excess protein in urine). Studies have shown that grade 3 (urine dipstick 4+, >3.5 g protein/24 hrs) and grade 4 (nephrotic syndrome) proteinuria have been common. In one study, 20% of patients experienced some form of proteinuria.
- Proteinuria usually develops approximately 6 months after starting bevacizumab treatment, and in some cases, it persists even after 11.2 months of follow-up. This led to the discontinuation of bevacizumab in one-third of patients.
- Analysis of multiple studies showed that nearly three-quarters of patients who received bevacizumab with chemotherapy also experienced proteinuria (urine dipstick 2+ or more than 1 g protein/24 hours, or nephrotic syndrome), which resolved in most of them.
- Bevacizumab was restarted in 42% of patients, but nearly half of them experienced a recurrence of proteinuria. In rare cases, patients who received bevacizumab developed nephrotic syndrome, which can be severe and even fatal.
- Kidney biopsy of patients with proteinuria showed consistent results with thrombotic microangiopathy. Comparative studies showed that patients who received bevacizumab had higher serum creatinine levels (1.5 to 1.91 times baseline) compared to chemotherapy alone.
- About one-third of patients did not return to their baseline creatinine levels after receiving bevacizumab. Proteinuria can be monitored through serial urine dipstick analyses, and 24-hour urine collection can be done for more accurate measurement if needed.
- If proteinuria is greater than 2g/24 hours, bevacizumab should be stopped, and it can be resumed if proteinuria levels are lower. Patients with nephrotic syndrome should stop taking bevacizumab. The 24-hour urine protein/creatinine ratio (UPCR) may not accurately correlate with actual urine protein levels.
Thromboembolism:
- When used together with chemotherapy, bevacizumab products can increase the chances of experiencing arterial thromboembolic (ATE) events, such as stroke and cerebral infarction (brain tissue damage due to lack of blood supply).
- Patients with glioblastoma (a type of brain tumor) had the highest rates of ATE. If you have a history of ATE, or diabetes, or if you are over 65 years old, you may be at an increased risk. Venous thromboembolism (VTE) is a risk for cancer patients in general, but a meta-analysis of 15 randomized trials showed that patients who received bevacizumab had a higher risk of developing VTE.
- Patients who received bevacizumab along with chemotherapy had a higher rate of grade 3 and higher VTEs compared to those who received chemotherapy alone.
- Patients who experience severe ATE, grade 4 VTE, or pulmonary embolism (blockage of lung arteries by blood clots) should stop taking bevacizumab. There are no studies on restarting bevacizumab after stopping for these reasons.
Wound healing complications [US Boxed Warning]:
- Patients who are treated with bevacizumab products are at a higher risk of experiencing complications related to wound healing and other surgical procedures. It is important to stop giving bevacizumab to patients who have wound healing problems and require surgery.
- Bevacizumab products should be discontinued at least 28 days before elective surgery. Patients should not receive bevacizumab products for more than 28 days after surgery or until the wound has fully healed.
- A controlled study showed that patients with colorectal cancer who underwent surgery and received bevacizumab within 28 days of major surgeries were more likely to experience complications related to wound healing, some of which were fatal.
- In a controlled clinical study involving patients with relapsed and recurrent glioblastoma, those who received bevacizumab had a higher incidence of wound healing events compared to those who did not receive it.
- A retrospective review of central vein access device placements found that combining port placement with the administration of bevacizumab within 14 days was more likely to cause wound dehiscence (separation of wound edges) compared to performing these procedures separately.
- It may be advisable to wait at least 6-8 weeks after discontinuing bevacizumab before undergoing major surgical procedures.
Renal impairment
- In a study that looked back at patients with kidney disease (CrCl = 60 mL/minute), it was found that those who had received bevacizumab as a treatment for renal cell carcinoma experienced an increase in blood pressure.
Monitoring parameters:
Keep a close eye on proteinuria and nephrotic syndrome by using urine dipstick tests. If the dipstick shows ≥2+ readings, collect a 24-hour urine sample for further monitoring.
Check blood pressure every 2 to 3 weeks, and more frequently if hypertension develops during treatment. Continue to monitor blood pressure even after discontinuing bevacizumab due to hypertension caused by the medication.
During the infusion, carefully monitor for signs and symptoms of an infusion reaction.
Be vigilant for signs and symptoms of GI perforation or fistula, such as abdominal pain, constipation, vomiting, fever, bleeding (including nosebleeds, coughing up blood, GI bleeding, or bleeding in the central nervous system), thromboembolism, wound healing complications, and heart failure.
AMD (off-label use):
- Keep a close watch on intraocular pressure and retinal artery perfusion.
- Watch out for symptoms of infectious endophthalmitis (infection inside the eye) and retinal detachment (separation of the retina from the back of the eye).
Diabetic macular edema (off-label use):
- Keep track of visual acuity (how well you can see), central subfield thickness (thickness of the central part of the retina), and intraocular pressure (pressure inside the eye).
- Be vigilant for signs and symptoms of infectious endophthalmitis (infection inside the eye), cataracts (clouding of the eye's lens), and retinal detachment (separation of the retina from the back of the eye).
Hereditary hemorrhagic telangiectasia (off-label use):
Before starting treatment and at 3 and 6 months after the first dose, the doctor will use ultrasound and CT scans of the liver to measure how well the heart is pumping blood and to check how the liver is responding to the treatment.
How to administer Bevacizumab (Avastin)?
Intravenous:
- Infuse the first dose of bevacizumab over 90 minutes. If the initial infusion is well tolerated, the second infusion may be administered over 60 minutes.
- If the 60-minute infusion is well tolerated, the third and subsequent infusions may be administered over 30 minutes.
- Once tolerance has been established at these infusion rates, some institutions may use an off-label 10-minute infusion rate for patients receiving bevacizumab at a dose of 5 mg/kg.
- In a study that looked at the safety of the 0.5 mg/kg/minute infusion rate, there was no increased risk of proteinuria or hypertension with the shorter infusion time.
- Do not administer dextrose solutions during the infusion. Monitor closely for signs and symptoms of an infusion reaction during the infusion.
- If a mild and clinically insignificant infusion reaction occurs, the infusion rate may be decreased.
- If a clinically significant infusion reaction occurs, the infusion should be stopped and resumed at a decreased infusion rate after symptoms have resolved.
- Bevacizumab should be withheld for severe infusion reactions.
Intravitreal injection (off-label use/route):
- Make sure the area is numb with local anesthesia and apply a broad-spectrum antimicrobial agent on the skin before starting the procedure.
Mechanism of action of Bevacizumab (Avastin):
Bevacizumab is a type of medicine that stops a protein called vascular endothelial growth factor (VEGF) from working. VEGF is important for the growth of blood vessels.
Bevacizumab prevents VEGF from binding to certain receptors on blood vessels, which stops the growth of new blood vessels.
This is believed to slow down the growth of all tissues, including cancerous tissue that has spread to other parts of the body.
Half-life elimination:
- Intravenous:
- Pediatric patients (age: 1 to 21 years): Median: 11.8 days (range: 4.4 to 14.6 days).
- Adults: ~20 days (range: 11 to 50 days)
- Intravitreal:
- ~5 to 10 days.
International Brand Names of Bevacizumab:
- Avastin
- Bevastim
- Bivastin
Bevacizumab Brand Names in Pakistan:
|
Bevacizumab Injection 100 mg in Pakistan |
|
|
Avastin |
Roche Pakistan Ltd. |
|
Bevacizumab Injection 400 mg in Pakistan |
|
|
Avastin |
Roche Pakistan Ltd. |
 Injection.webp)