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  • Mvasi
    / Amgen


    Active Ingredient
    Bevacizumab 25 mg/ml

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    1× 4 (100 mg), 16 ml (400 mg)

    not in the basket chart

    Dosage

    Metastatic carcinoma of the colon or rectum (mCRC)
    The recommended dose of MVASI, 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.
    Metastatic breast cancer (mBC)
    The recommended dose of MVASI 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.
    Non-small cell lung cancer (NSCLC)
    First-line treatment of non-squamous NSCLC in combination with platinum-based chemotherapy
    MVASI is administered in addition to platinum-based chemotherapy for up to 6 cycles of treatment followed by MVASI as a single agent until disease progression.
    The recommended dose of MVASI 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.
    First-line treatment of non-squamous NSCLC with EGFR activating mutations in combination with erlotinib
    EGFR mutation testing should be performed prior to initiation of treatment with the combination of MVASI and erlotinib. It is important that a well-validated and robust methodology is chosen to avoid false negative or false positive determinations.
    The recommended dose of MVASI when used in addition to erlotinib is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.
    It is recommended that the treatment with MVASI in addition to erlotinib is continued until disease progression.
    For the posology and method of administration of erlotinib, please refer to the full erlotinib prescribing information.
    Advanced and/or metastatic renal cell cancer (mRCC)
    The recommended dose of MVASI 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.
    Malignant Glioma (WHO Grade IV)- Glioblastoma
    The recommended dose of MVASI administered as an intravenous infusion is 10 mg/kg of body weight given once every 2 weeks 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.
    Epithelial ovarian, fallopian tube and primary peritoneal cancer
    Front-line treatment: MVASI is administered in addition to carboplatin and paclitaxel for up to 6 cycles of treatment followed by continued use of MVASI as single agent until disease progression or for a maximum of 15 months or until unacceptable toxicity, whichever occurs earlier.
    The recommended dose of MVASI is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.
    Treatment of platinum-sensitive recurrent disease: MVASI is administered in combination with carboplatin and gemcitabine for 6 cycles and up to 10 cycles followed by continued use of MVASI as single agent until disease progression. The recommended dose of MVASI is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion.
    Treatment of platinum-resistant recurrent disease: MVASI is administered in combination with one of the following agents – paclitaxel, topotecan (given weekly) or pegylated liposomal doxorubicin. The recommended dose of MVASI is 10 mg/kg of body weight given once every 2 weeks as an intravenous weeks), the recommended dose of MVASI is 15 mg/kg of body weight given once every 3 weeks as an intravenous infusion. It is recommended that treatment be continued until disease progression or unacceptable toxicity.
    Cervical cancer
    MVASI is administered in combination with one of the following chemotherapy regimens: paclitaxel and cisplatin or paclitaxel and topotecan.
    The recommended dose of MVASI is 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.
    Special populations
    Elderly patients: No dose adjustment is required in the elderly.
    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.
    Pediatric population
    The safety and efficacy of bevacizumab in children less than 18 years old have not been established.
    Method of administration: See prescribing information for full details.


    Indications

    MVASI in combination with fluoropyrimidine-based chemotherapy is indicated for treatment of adult patients with metastatic carcinoma of the colon or rectum.
    MVASI in combination with paclitaxel is indicated for first-line treatment of adult patients with metastatic breast cancer. For further information as to human epidermal growth factor receptor 2 (HER2) status.
    MVASI, in addition to platinum-based chemotherapy, is indicated for first-line treatment of adult patients with unresectable advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology.
    MVASI, 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.
    MVASI in combination with interferon alfa-2a is indicated for first-line treatment of adult patients with advanced and/or metastatic renal cell cancer.
    MVASI, as a single agent, is indicated for the treatment of glioblastoma in patients with progressive disease following prior therapy.
    MVASI, 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).
    MVASI, 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.
    MVASI in combination with paclitaxel, topotecan, or pegylated liposomal doxorubicin is indicated for the treatment of adult patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than two prior chemotherapy regimens and who have not received prior therapy with bevacizumab or other VEGF inhibitors or VEGF receptor-targeted agents.
    MVASI, in combination with paclitaxel and cisplatin or, paclitaxel and topotecan is indicated in patients who cannot receive platinum therapy, for the treatment of adult patients with persistent, recurrent, or metastatic carcinoma of the cervix.


    Contra-Indications

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


    Special Precautions

    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, therefore, caution should be exercised when treating these patients. Prior radiation is a risk factor for GI perforation in patients treated for persistent, recurrent or metastatic cervical cancer with MVASI and all patients with GI perforation had a history of prior radiation. Therapy should be permanently discontinued in patients who develop gastrointestinal perforation.
    GI-vaginal fistulae in study GOG-0240
     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). Prior radiation is a major risk factor for the development of GI-vaginal fistulae and all patients with GI-vaginal fistulae had a history of prior radiation. Recurrence of cancer within the field of prior radiation is an additional important risk factor for the development of GI-vaginal fistulae.
    Non-GI fistulae
    Patients may be at increased risk for the development of fistulae when treated with bevacizumab. Permanently discontinue MVASI in patients with tracheoesophageal (TE) fistula or any grade 4 fistula.
    Limited information is available on the continued use of bevacizumab in patients with other fistulae. In cases of internal fistula not arising in the gastrointestinal tract, discontinuation of MVASI 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.
    Necrotizing 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. MVASI 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. Pre-existing hypertension should be adequately controlled before starting MVASI treatment. There is no information on the effect of bevacizumab 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 6 hypertension is not advised in patients who receive a cisplatin-based chemotherapy regimen. MVASI 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 MVASI. 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 bevacizumab. There is evidence suggesting that all grade (US National Cancer Institute-Common Terminology Criteria for Adverse Events [NCI-CTCAE v.3]) proteinuria may be related to the dose. Monitoring of proteinuria by dipstick urinalysis is recommended prior to starting and during therapy. Grade 4 proteinuria (nephrotic syndrome) was seen in up to 1.4% of patients treated with bevacizumab. Therapy should be permanently discontinued in patients who develop nephrotic syndrome (NCI-CTCAE v.3).
     Arterial thromboembolism
    In clinical trials, the incidence of arterial thromboembolic reactions including cerebrovascular accidents (CVAs), transient ischemic attacks (TIAs) and myocardial infarctions (MIs) was higher in patients receiving bevacizumab in combination with chemotherapy compared to those who received chemotherapy alone. Patients receiving bevacizumab plus chemotherapy, with a history of arterial thromboembolism, diabetes or age greater than 65 years have an increased risk of developing arterial thromboembolic reactions during therapy. Caution should be taken when treating these patients with MVASI. 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. Patients treated for persistent, recurrent, or metastatic cervical cancer with bevacizumab in combination with paclitaxel and cisplatin may be at increased risk of venous thromboembolic events.
    MVASI should be discontinued in patients with life-threatening (grade 4) thromboembolic reactions, including pulmonary embolism (NCI-CTCAE v.3). Patients with thromboembolic reactions ≤ grade 3 need to be closely monitored (NCI-CTCAE v.3).
    Hemorrhage
    Patients treated with bevacizumab have an increased risk of hemorrhage, especially tumor-associated hemorrhage. MVASI should be discontinued permanently in patients who experience grade 3 or 4 bleeding during bevacizumab therapy (NCI-CTCAE v.3). Pulmonary hemorrhage/hemoptysis Patients with non-small cell lung cancer treated with bevacizumab may be at risk of serious, and in some cases fatal, pulmonary hemorrhage/hemoptysis. Patients with recent pulmonary hemorrhage/hemoptysis (> 2.5 mL of red blood) should not be treated with bevacizumab. Aneurysms and artery dissections The use of VEGF pathway inhibitors in patients with or without hypertension may promote the formation of aneurysms and/or artery dissections. Before initiating MVASI, this risk should be carefully considered in patients with risk factors such as hypertension or history of aneurysm.
    Congestive heart failure (CHF)
    Reactions consistent with CHF were reported in clinical trials. The findings ranged from asymptomatic declines in left ventricular ejection fraction to symptomatic CHF, requiring treatment or hospitalization. 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. Most of the patients who experienced CHF had metastatic breast cancer and had received previous treatment with anthracyclines, prior radiotherapy to the left chest wall or other risk factors for CHF were present.
    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 8 chemotherapy regimens plus bevacizumab in comparison to chemotherapy alone. This has mainly been seen in combination with platinum- or taxane-based therapies in the treatment of NSCLC, mBC, and in combination with paclitaxel and topotecan in persistent, recurrent, or metastatic cervical cancer.
    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 humanized monoclonal antibody. If a reaction occurs, the infusion should be discontinued and appropriate medical therapies should be administered. A systematic premedication is not warranted.
    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. Caution should be exercised when bevacizumab and intravenous bisphosphonates are administered simultaneously or sequentially. Invasive dental procedures are also an identified risk factor. A dental examination and appropriate preventive dentistry should be considered prior to starting the treatment with MVASI. In patients who have previously received or are receiving intravenous bisphosphonates invasive dental procedures should be avoided, if possible.
    Intravitreal
    MVASI is not formulated for intravitreal use. Ovarian failure/fertility Bevacizumab may impair female fertility. Therefore fertility preservation strategies should be discussed with women of childbearing potential prior to starting treatment with bevacizumab.
    Sodium content
    MVASI 25 mg/mL concentrate for solution for infusion (4 mL)See prescribing information for full details.


    Side Effects

    Hypertension, fatigue or asthenia, diarrhea and abdominal pain. See prescribing information for full details.

     


    Drug interactions

    Effect of antineoplastic agents on bevacizumab pharmacokinetics

    No clinically relevant interaction of co-administered chemotherapy on bevacizumab pharmacokinetics was observed based on the results of population pharmacokinetic analyzes.
    See prescribing information for full details.


    Pregnancy and Lactation

    There are no clinical trial data on the use of bevacizumab in pregnant women. Studies in animals have shown reproductive toxicity including malformations.
    Lactation
    It is not known whether bevacizumab is excreted in human milk.


    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.

     


    Important notes

    Store in a refrigerator (2°C – 8°C).
    Do not freeze.
    Keep the vial in the outer carton in order to protect from light.
    See prescribing information for full details. 


    Manufacturer
    Amgen Europe B.V., Breda, Netherlands.
    Licence holder
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