Avastin

/ Roche

Metastatic carcinoma of the colon or rectum (mCRC): The recommended dose of Bevacizumab, administered as an intravenous infusion, is either 5 mg/kg or 10 mg/kg of body weight given once every 2 weeks or 7.5 mg/kg or 15 mg/kg of body weight given once every 3 weeks. It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity. See prescribing information for full details.
Metastatic breast cancer (mBC): The recommended dose of Bevacizumab is 10 mg/kg of body weight given once every 2 weeks or 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion. It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity. See prescribing information for full details.
Non-small cell lung cancer (NSCLC): Bevacizumab is administered in addition to platinum-based chemotherapy for up to 6 cycles of treatment followed by Bevacizumab as a single agent until disease progression. The recommended dose of Bevacizumab is 7.5 mg/kg or 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion. Clinical benefit in NSCLC patients has been demonstrated with both 7.5 mg/kg and 15 mg/kg doses. It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity. See prescribing information for full details.
Advanced and/or metastatic Renal Cell Cancer (mRCC): The recommended dose of Bevacizumab is 10 mg/kg of body weight given once every 2 weeks as an intravenous infusion. It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity. See prescribing information for full details.
Malignant Glioma (WHO Grade IV )- Glioblastoma: The recommended dose of Bevacizumab is 10 mg/kg of body weight given once every 2 weeks or 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion. It is recommended that treatment be continued until progression of the underlying disease or until unacceptable toxicity. See prescribing information for full details.
Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer: Bevacizumab is administered in addition to carboplatin and paclitaxel for up to 6 cycles of treatment followed by continued use of Bevacizumab as single agent until disease progression or for a maximum of 15 months or until unacceptable toxicity, whichever occurs earlier. The recommended dose of Bevacizumab is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion. See prescribing information for full details.
Treatment of recurrent disease: Bevacizumab is administered in combination with carboplatin and gemcitabine for 6 cycles and up to 10 cycles followed by continued use of Bevacizumab as single agent until disease progression.The recommended dose of Bevacizumab is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion. See prescribing information for full details.
Special Populations
Elderly patients: No dose adjustment is required in the elderly.
Pediatric population: The safety and efficacy of Bevacizumab in children and adolescents have not been established. Bevacizumab is not approved for use in patients under the age of 18 years.
Patients with renal impairment: The safety and efficacy have not been studied in patients with renal impairment.
Patients with hepatic impairment: The safety and efficacy have not been studied in patients with hepatic impairment.
Method of administration: The initial dose should be delivered over 90 minutes as an intravenous infusion. If the first infusion is well tolerated, the second infusion may be administered over 60 minutes. If the 60-minute infusion is well tolerated, all subsequent infusions may be administered over 30 minutes. It should not be administered as an intravenous push or bolus. The necessary amount of Bevacizumab should be withdrawn and diluted to the required administration volume with sodium chloride 9 mg/ml (0.9%) solution for injection. The concentration of the final Bevacizumab solution should be kept within the range of 1.4 mg/ml to 16.5 mg/ml. Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration. This drug for single-use only, as the product contains no preservatives. Any unused medicinal product or waste material should be disposed in accordance with local requirements. No incompatibilities between this drug and polyvinyl chloride or polyolefine bags or infusion sets have been observed.

The drug in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of patients with metastatic carcinoma of the colon or rectum.
In combination with Paclitaxel is indicated for first-line treatment of patients with metastatic breast cancer.
In addition to platinum-based chemotherapy, is indicated for first-line treatment of patients with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology.
In combination with interferon alfa-2a is indicated for first line treatment of patients with advanced and/or metastatic renal cell cancer.
As a single agent, is indicated for the treatment of glioblastoma in patients with progressive disease following prior therapy.
In combination with Carboplatin and Paclitaxel, is indicated for the front-line treatment of advanced (FIGO stages III B, III C and IV) epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are at high risk for recurrence (residual disease after debulking).
In combination with Carboplatin and Gemcitabine, is indicated for treatment of adult patients with first recurrence of platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer who have not received prior therapy with Bevacizumab or other VEGF inhibitors or VEGF receptor–targeted agents.
See prescribing information for full details.

Hypersensitivity to the active substance or to any of the excipients.
Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies, Pregnancy.

Gastrointestinal perforations: Patients may be at an increased risk for the development of gastrointestinal perforation and gall bladder perforation when treated with Bevacizumab. Intra-abdominal inflammatory process may be a risk factor for gastrointestinal perforations in patients with metastatic carcinoma of the colon or rectum, therefore, caution should be exercised when treating these patients. Therapy should be permanently discontinued in patients who develop gastrointestinal.
Fistulae: Patients may be at increased risk for the development of fistulae when treated with Bevacizumab. Permanently discontinue this drug in patients with tracheoesophageal (TE) fistula or any Grade 4 fistula . Limited information is available on the continued use of this drug  in patients with other fistulae.
n cases of internal fistula not arising in the gastrointestinal (GI) tract, discontinuation of the drug should be considered.
Wound healing complications: Bevacizumab may adversely affect the wound healing process. Therapy should not be initiated for at least 28 days following major surgery or until the surgical wound is fully healed. In patients who experienced wound healing complications during therapy, treatment should be withheld until the wound is fully healed. Therapy should be withheld for elective surgery.
Necrotising fasciitis, including fatal cases, has rarely been reported in patients treated with Bevacizumab. This condition is usually secondary to wound healing complications, gastrointestinal perforation or fistula formation. Bevacizumab therapy should be discontinued in patients who develop necrotising fasciitis, and appropriate treatment should be promptly initiated.
Hypertension: An increased incidence of hypertension was observed in Bevacizumab-treated patients. Clinical safety data suggest that the incidence of hypertension is likely to be dose-dependent. Preexisting hypertension should be adequately controlled before starting Bevacizumab treatment.
There is no information on the effect of this drug in patients with uncontrolled hypertension at the time of initiating therapy. Monitoring of blood pressure is generally recommended during therapy.
In most cases hypertension was controlled adequately using standard antihypertensive treatment appropriate for the individual situation of the affected patient. The use of diuretics to manage hypertension is not advised in patients who receive a cisplatin-based chemotherapy regimen. This drug should be permanently discontinued if medically significant hypertension cannot be adequately controlled with antihypertensive therapy, or if the patient develops hypertensive crisis or hypertensive encephalopathy.
Posterior Reversible Encephalopathy Syndrome (PRES): There have been rare reports of Bevacizumab-treated patients developing signs and symptoms that are consistent with PRES, a rare neurologic disorder, which can present with the following signs and symptoms among others: seizures, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). In patients developing PRES, treatment of specific symptoms including control of hypertension is recommended along with discontinuation of this drug. The safety of reinitiating Bevacizumab therapy in patients previously experiencing PRES is not known.
Proteinuria: Patients with a history of hypertension may be at increased risk for the development of proteinuria when treated with this drug. There is evidence suggesting that all Grade proteinuria may be related to the dose. Monitoring of proteinuria by dipstick urinalysis is recommended prior to starting and during therapy. Therapy should be permanently discontinued in patients who develop Grade 4 proteinuria (nephrotic syndrome). See prescribing information for full details.
Arterial thromboembolism: In clinical trials, the incidence of arterial thromboembolic reactions including cerebrovascular accidents (CVAs), transient ischaemic attacks (TIAs) and myocardial infarctions (MIs) was higher in patients receiving Bevacizumab in combination with chemotherapy compared to those who received chemotherapy alone.
Venous thromboembolism: The incidence of venous thromboembolic reactions in clinical trials was similar in patients receiving Bevacizumab in combination with chemotherapy compared to those receiving the control chemotherapy alone. Venous thromboembolic reactions include deep venous thrombosis, pulmonary embolism and thrombophlebitis. Patients who have experienced a venous thromboembolic reaction may be at higher risk for a recurrence if they receive Bevacizumab in combination with chemotherapy versus chemotherapy alone.
Congestive heart failure (CHF): In clinical trials with Avastin, congestive heart failure (CHF) was observed in all cancer indications studied to date, but occurred predominantly in patients with metastatic breast cancer. See prescribing information for full details. Most patients who developed CHF during mBC trials showed improved symptoms and/or left ventricular function following appropriate medical therapy. See prescribing information for full details.
Hypersensitivity reactions/infusion reactions: In some clinical trials anaphylactic and anaphylactoid-type reactions were reported more frequently in patients receiving this drug in combination with chemotherapy than with chemotherapy alone. The incidence of these reactions in some clinical trials of Bevacizumab is common (up to 5% in Bevacizumab-treated patients).
Laboratory abnormalities: Decreased neutrophil count, decreased white blood cell count and presence of urine protein may be associated with Bevacizumab treatment.
See prescribing information for full details.

Sepsis, abscess, infection, febrile neutropenia, leucopenia, thrombocytopenia, neutropenia, anaemia, dehydration, anorexia,peripheral sensory neuropathy, cerebrovascular accident syncope, somnolence, dysgeusia, headache, dysarthria, Headache, eye disorder, lacrimation increased, cardiac failure, congestive supraventricular tachycardia, hypertension, thromboembolism, deep vein thrombosis haemorrhage, pulmonary embolism, dyspnoea, hypoxia, epistaxis, rhinitis, diarrhoea, nausea, vomiting, intestinal perforation ileus intestinal obstruction abdominal pain gastrointestinal disorder, stomatitis, constipation, rectal haemorrhage, palmar-plantar erythrodysaesthesia syndrome, exfoliative dermatitis,dry skin, skin discolouration, muscular weakness, myalgia, arthralgia, asthenia, fatigue,uti, pyrexia, asthenia pain, mucosal inflammation.
See prescribing information for full details.

There was neither statistical significance nor clinically relevant difference in clearance of this drug in patients receiving Bevacizumab monotherapy compared to patients receiving Bevacizumab in combination with interferon alfa-2a or other chemotherapies (IFL, 5- FU/LV, carboplatin/paclitaxel, capecitabine, doxorubicin or cisplatin/gemcitabine.
Combination of Bevacizumab and sunitinib malate: In two clinical trials of metastatic renal cell carcinoma, microangiopathic haemolytic anaemia (MAHA) was reported in 7 of 19 patients treated with Bevacizumab (10 mg/kg every two weeks) and sunitinib malate (50 mg daily) combination. MAHA is a haemolytic disorder which can present with red cell fragmentation, anaemia, and thrombocytopenia. In addition, hypertension (including hypertensive crisis), elevated creatinine, and neurological symptoms were observed in some of these patients. All of these findings were reversible upon discontinuation of Bevacizumab and sunitinib malate. See prescribing information for full details.
Combination with platinum- or taxane-based therapies: Increased rates of severe neutropenia, febrile neutropenia, or infection with or without severe neutropenia (including some fatalities) have been observed mainly in patients treated with platinum- or taxane-based therapies in the treatment of NSCLC and mBC.
Radiotherapy: The safety and efficacy of concomitant administration of radiotherapy and this drug has not been established.
EGFR monoclonal antibodies in combination with Bevacizumab chemotherapy regimens: No interaction studies have been performed. EGFR monoclonal antibodies should not be administered for the treatment of mCRC in combination with Bevacizumab-containing chemotherapy. Results from the randomised phase III studies, PACCE and CAIRO-2, in patients with mCRC suggest that the use of anti-EGFR monoclonal antibodies panitumumab and cetuximab, respectively, in combination with Bevacizumab plus chemotherapy, is associated with decreased PFS and/or OS, and with increased toxicity compared with Bevacizumab plus chemotherapy alone.
See prescribing information for full details.

Pregnancy: There are no data on the use of Bevacizumab in pregnant women. Studies in animals have shown reproductive toxicity including malformations. IgGs are known to cross the placenta, and it is anticipated to inhibit angiogenesis in the foetus, and thus is suspected to cause serious birth defects when administered during pregnancy. Bevacizumab is contraindicated in pregnancy.
Breast-feeding: It is not known whether Bevacizumab is excreted in human milk. As maternal IgG is excreted in milk and Bevacizumab could harm infant growth and development, women must discontinue breast-feeding during therapy and not breast-feed for at least six months following the last dose of Bevacizumab.

The highest dose tested in humans (20 mg/kg of body weight, intravenous every 2 weeks) was associated with severe migraine in several patients. 

Compatibilities: Avastin infusions should not be administered or mixed with glucose solutions. This medicinal product must not be mixed with other medicinal products except those mentioned above. See prescribing information for full details.
Storage: Store in a refrigerator (2°C-8°C), do not freeze.
Keep the vial in the outer carton in order to protect from light.
Chemical and physical in-use stability has been demonstrated for 48 hours at 2°C to 30°C in sodium chloride 9 mg/ml (0.9%) solution for injection. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
See prescribing information for full details.