Safety Information

Bevacizumab is to be prescribed by a Registered Medical Practitioner only. Consult your local Registered Medical Practitioner before any usage.

Indications and Usage

Bevacizumab is indicated for the following:

Metastatic Colorectal Cancer (mCRC)

Bevacizumab, in combination with intravenous 5-fluorouracil-based chemotherapy, is indicated for the first- or second-line treatment of adult patients with metastatic colorectal cancer.

Bevacizumab, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Versavo^® containing regimen.

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

First-Line Non-Squamous Non–Small Cell Lung Cancer (NSCLC)

Bevacizumab, in combination with carboplatin and paclitaxel, is indicated for the first-line treatment of adult patients with unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer.

Bevacizumab, in combination with erlotinib, is indicated for first-line treatment of adult patients with unresectable advanced, metastatic or recurrent non-squamous non-small cell lung cancer with Epidermal Growth Factor Receptor (EGFR) activating mutations.

Recurrent Glioblastoma (GBM)

Bevacizumab is indicated for the treatment of recurrent glioblastoma in adults.

Metastatic Renal Cell Carcinoma (mRCC)

Bevacizumab, in combination with interferon alfa, is indicated for the treatment of metastatic renal cell carcinoma in adult patients.

Persistent, Recurrent, or Metastatic Cervical Cancer

Bevacizumab, in combination with paclitaxel and cisplatin or paclitaxel and topotecan, is indicated for the treatment of adult patients with persistent, recurrent, or metastatic cervical cancer.

Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Bevacizumab, in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan, is indicated for the treatment of adult patients with platinum-resistant recurrent ezpithelial ovarian, fallopian tube or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens.

Bevacizumab, in combination with carboplatin and paclitaxel, or with carboplatin and gemcitabine, followed by Bevacizumab as a single agent, is indicated for the treatment of patients with platinum sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Metastatic Breast Cancer

Bevacizumab in combination with paclitaxel is indicated for first-line treatment of adult patients with metastatic breast cancer.

Bevacizumab in combination with capecitabine is indicated for first-line treatment of adult patients with metastatic breast cancer in whom treatment with other chemotherapy options including taxanes or anthracyclines is not considered appropriate. Patients who have received taxane and anthracycline containing regimens in the adjuvant setting within the last 12 months should be excluded from treatment with Bevacizumab in combination with capecitabine.

Possible Serious Side Effects with Versavo^®

Like all medications, few patients on this medication may experience few side effects. Some of these may be serious leading to hospitalization. Your treating doctor may decide to stop therapy in case of intolerance to side effects.

Important side effects with Versavo^® treatment are as follows:

Gastrointestinal (GI) perforations and Fistulae

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. Therapy should be permanently discontinued in patients who develop gastrointestinal perforation.

GI-vaginal Fistulae

Patients treated for persistent, recurrent, or metastatic cervical cancer with bevacizumab are at increased risk of fistulae between the vagina and any part of the GI tract (Gastrointestinal-vaginal fistulae).

Non-GI Fistulae

Patients may be at increased risk for the development of fistulae when treated with bevacizumab.

Permanently discontinue bevacizumab in patients with tracheoesophageal (TE) fistula or any Grade 4 fistula. In cases of internal fistula not arising in the gastrointestinal tract, discontinuation of bevacizumab should be considered.

Wound healing complications

Bevacizumab may adversely affect the wound healing process. Serious wound healing complications, including anastomotic complications, with a fatal outcome have been reported. 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.

Hypertension

An increased incidence of hypertension was observed in bevacizumab-treated patients. Pre-existing hypertension should be adequately controlled before starting bevacizumab treatment. Monitoring of blood pressure is generally recommended during therapy.

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

Renal Injury and Proteinuria

Patients with a history of hypertension may be at increased risk for the development of proteinuria when treated with bevacizumab. Monitoring of proteinuria by dipstick urinalysis is recommended prior to starting and during therapy. Therapy should be permanently discontinued in patients who develop nephrotic syndrome (NCI-CTCAE v.3).

Arterial thromboembolism

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.

Therapy should be permanently discontinued in patients who develop arterial thromboembolic reactions.

Venous thromboembolism

Patients may be at risk of developing venous thromboembolic reactions, including pulmonary embolism under bevacizumab treatment.

Bevacizumab should be discontinued in patients with life-threatening (Grade 4) thromboembolic reactions, including pulmonary embolism. Patients with thromboembolic reactions ≤ Grade 3 need to be closely monitored.

Haemorrhage

Patients treated with bevacizumab have an increased risk of haemorrhage, especially tumour-associated haemorrhage. Bevacizumab should be discontinued permanently in patients who experience Grade 3 or 4 bleeding during bevacizumab therapy.

Patients should be monitored for signs and symptoms of CNS bleeding, and bevacizumab treatment discontinued in cases of intracranial bleeding.

Pulmonary haemorrhage/haemoptysis

Patients with non-small cell lung cancer treated with bevacizumab may be at risk of serious, and in some cases fatal, pulmonary haemorrhage/haemoptysis.

Congestive heart failure (CHF)

Reactions consistent with CHF were reported with bevacizumab. The findings ranged from asymptomatic declines in left ventricular ejection fraction to symptomatic CHF, requiring treatment or hospitalisation. Caution should be exercised when treating patients with clinically significant cardiovascular disease such as pre-existing coronary artery disease, or congestive heart failure with bevacizumab.

Neutropenia and infections

Increased rates of severe neutropenia, febrile neutropenia, or infection with or without severe neutropenia (including some fatalities) have been observed in patients treated with some myelotoxic chemotherapy regimens plus bevacizumab in comparison to chemotherapy alone.

Hypersensitivity reactions/infusion reactions

Patients may be at risk of developing infusion/hypersensitivity reactions. Close observation of the patient during and following the administration of bevacizumab is recommended as expected for any infusion of a therapeutic humanised monoclonal antibody. If a reaction occurs, the infusion should be discontinued and appropriate medical therapies should be administered.

Osteonecrosis of the jaw (ONJ)

Cases of ONJ have been reported in cancer patients treated with bevacizumab, the majority of whom had received prior or concomitant treatment with intravenous bisphosphonates, for which ONJ is an identified risk.

Intravitreal use and Eye disorders

Bevacizumab is not formulated for intravitreal use. Individual cases and clusters of serious ocular adverse reactions have been reported following unapproved intravitreal use of bevacizumab compounded from vials approved for intravenous administration in cancer patients. These reactions included infectious endophthalmitis, intraocular inflammation such as sterile endophthalmitis, uveitis and vitritis, retinal detachment, retinal pigment epithelial tear, intraocular pressure increased, intraocular haemorrhage such as vitreous haemorrhage or retinal haemorrhage and conjunctival haemorrhage. Some of these reactions have resulted in various degrees of visual loss, including permanent blindness.

Ovarian failure/fertility

Bevacizumab may impair female fertility. Therefore fertility preservation strategies should be discussed with women of child-bearing potential prior to starting treatment with bevacizumab.

Effects on ability to drive and use machines

Bevacizumab has no or negligible influence on the ability to drive and use machines. However, somnolence and syncope have been reported with bevacizumab use (see table 1 in section 4.8). If patients are experiencing symptoms that affect their vision or concentration, or their ability to react, they should be advised not to drive and use machines until symptoms abate.

Other very commonly seen side effects of Bevacizumab (may affect more than 1 in 10 people)

You should seek help immediately if you suffer from any of the below mentioned side effects.

Severe side effects, which may be very common (affects more than 1 user in 10), include:

For a full list of reported side effects, please see the Prescribing Information.

Contraindications

Versavo^® is contraindicated in the following conditions:

• Hypersensitivity to the active substance or to any of the excipients (α,α-Trehalose dehydrate, Sodium Phosphate, Polysorbate 20 and Water for injections).
• Hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.
• Pregnancy.
• In patients with untreated central nervous system (CNS) metastases.

Overdose

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

Incompatibilities

This medicinal product must not be mixed with other medicinal products except 0.9 % sodium chloride solution.

A concentration dependent degradation profile of bevacizumab was observed when diluted with glucose solutions (5%).

For more information, please refer to the full Prescribing Information for VERSAVO^®. You should contact your doctor immediately if you have any of the side effects mentioned above.

You are encouraged to report side effects to safetybiologicals@drreddys.com