bevacizumab (Rx)

Brand and Other Names:Avastin, Mvasi, more...bevacizumab-awwb
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution

  • 25mg/mL (4-mL, 16-mL single dose vials)

Biosimilar to Avastin

  • Mvasi (bevacizumab-awwb)
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Metastatic Colorectal Cancer

Avastin, Mvasi

Indicated for first-line and second-line treatment for metastatic colorectal carcinoma (in combination with 5-fluorouracil-based chemotherapy)

Recommended doses in combination with the following chemotherapy:

Fluorouracil based chemotherapy: 5-10 mg/kg IV q2Weeks  

Bolus-IFL (ie, irinotecan, 5-FU, leucovorin): 5 mg/kg IV q2Weeks

FOLFOX4 (ie, oxaliplatin, 5-FU, leucovorin): 10 mg/kg IV q2Weeks

Second-line continuation treatment with bevacizumab

  • Indicated for second-line treatment in patients who have progressed on a first-line bevacizumab-containing regimen
  • Use bevacizumab in combination with a fluoropyrimidine (eg, 5-FU, capecitabine) plus irinotecan or oxaliplatin-based chemotherapy
  • 5 mg/kg IV q2Weeks or 7.5 mg/kg IV q3Weeks

Non-Small Cell Lung Cancer

Avastin, Mvasi

Indicated for unresectable, locally advanced, recurrent or metastatic, nonsquamous NSCLC in combination with carboplatin and paclitaxel

15 mg/kg IV q3Weeks 

Breast Cancer

Indication for metastatic breast cancer (HER2-negative) revoked by FDA in November 2011 due to failure to delay tumor growth or provide survival benefit

Renal Cell Carcinoma

Avastin, Mvasi

Indicated for metastatic renal cell carcinoma in combination with interferon alfa-2a

10 mg/kg IV q2Weeks (Avastin may be used as monotherapy off-label) 

Cervical Cancer

Avastin, Mvasi

Indicated as part of a combination chemotherapy regimen for persistent, recurrent, or metastatic cervical cancer 

15 mg/kg IV q3Weeks in combination with 1 of the following chemotherapy regimens: paclitaxel and cisplatin, or paclitaxel and topotecan

Ovarian, Fallopian Tube, or Peritoneal Cancer

Avastin

Platinum-resistant

  • Indicated in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for women with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens
  • Bevacizumab 10 mg/kg IV q2Weeks in combination with 1 of the following IV chemotherapy regimens: paclitaxel, pegylated liposomal doxorubicin, or topotecan weekly OR
  • Bevacizumab 15 mg/kg IV q3Weeks in combination with topotecan q3Weeks 

Platinum-sensitive

  • Indicated for women with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer either in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine chemotherapy, followed by bevacizumab alone
  • Women are said to be 'platinum-sensitive' if a relapse occurs ≥6 months following the last treatment with a platinum-based chemotherapy
  • Bevacizumab 15 mg/kg IV q3Weeks in combination with carboplatin and paclitaxel for 6-8 cycles, followed by continued use of bevacizumab 15 mg/kg q3Weeks as a single agent until disease progression, OR
  • Bevacizumab 15 mg/kg IV q3Weeks in combination with carboplatin and paclitaxel for 6-8 cycles, followed by continued use of bevacizumab 15 mg/kg q3Weeks as a single agent until disease progression, OR

Treatment of stage III or IV disease following initial surgical resection

  • Indicated in combination with carboplatin and paclitaxel, followed by bevacizumab as a single agent, for patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection
  • Bevacizumab 15 mg/kg IV q3Weeks in combination with carboplatin and paclitaxel for up to 6 cycles, followed by bevacizumab 15 mg/kg q3Weeks as a single agent, for a total of up to 22 cycles or until disease progression, whichever occurs earlier

Glioblastoma

Avastin

  • Indicated for the treatment of recurrent glioblastoma
  • 10 mg/kg IV q2Weeks 

Mvasi

  • Indicated for glioblastoma as a single agent for patients with progressive disease following prior therapy
  • 10 mg/kg IV q2Weeks 
  • Effectiveness of bevacizumab products in glioblastoma is based on an improvement in objective response rate; no data demonstrating an improvement in disease-related symptoms or increased survival with bevacizumab products

Exudative ARMD (Off-label)

Off-label indication for exudative age-related macular degeneration

Off-label: 1.25 mg (in 0.05mL of solution) administered by intravitreal injection once monthly

Reference: CATT Research Group, N Engl J Med 2011;364:1897-1908

The need to repackage the drug from the available size vial into a smaller doses increases risk for transmission of infection if improper aseptic technique occurrs

Dosage Modifications

Discontinue treatment

  • Gastrointestinal perforation, any grade
  • Tracheoesophageal fistula, any grade
  • Grade 4 fistula
  • Fistula formation involving any internal organ
  • Wound healing complications requiring medical intervention
  • Necrotizing fasciitis
  • Grade 3 or 4 hemorrhage
  • Severe arterial thromboembolic events
  • Grade 4 venous thromboembolic events, including pulmonary embolism
  • Hypertensive crisis or hypertensive encephalopathy
  • Posterior Reversible Encephalopathy Syndrome (PRES)
  • Nephrotic syndrome
  • Severe infusion reactions
  • Congestive heart failure

Withhold treatment

  • Recent history of hemoptysis ≥1/2 tsp (2.5 mL)
  • Severe hypertension not controlled with medical management; resume once controlled
  • Proteinuria ≥2 grams/24 hr in absence of nephrotic syndrome; withhold until proteinuria <2 grams/24 hr

Infusion reaction

  • Mild, clinically significant: Decrease infusion rate
  • Clinically significant: Interrupt infusion; resume at a decreased rate of infusion after symptoms resolve

Dosing Considerations

Limitation of use (colorectal cancer): Not indicated for adjuvant treatment of colon cancer

Orphan Designations

Coadministration with platinum-based antineoplastic and fluorouracil or capecitabine for treatment of stomach cancer

Melanoma stages IIb-IV

Hereditary hemorrhagic telangiectasia

Pancreatic cancer

Mesothelioma

Coat disease

Sponsor

  • Genentech, Inc; 1 DNA Way; South San Francisco, CA 94080-4990
  • MicroSert, Ltd; Bar Yehuda Street; Nesher (Coat disease)

Safety and efficacy not established

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Interactions

Interaction Checker

and bevacizumab

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
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            Adverse Effects

            >10% (Epithelial ovarian, fallopian tube or primary peritoneal cancer)

            Treatment following resection

            • Fatigue (72-80%)
            • Nausea (53-58%)
            • Arthralgia (33-41%)
            • Diarrhea (38-40%)
            • Headache (26-34%)
            • Hypertension (24-32%)
            • Epistaxis (30-31%)
            • Dyspnea (26-28%)
            • Stomatitis (19-25%)
            • Pain in extremity (19-25%)
            • Muscular weakness (13-15%)
            • Dysarthria (10-12%)

            Platinum-resistant

            • Neutropenia, Grade 2-4 (31%)
            • Hypertension, Grade 2-4 (19%)
            • Peripheral sensory neuropathy, Grade 2-4 (18%)
            • Mucosal inflammation, Grade 2-4 (13%)
            • Proteinuria, Grade 2-4 (12%)
            • Infection, Grade 2-4 (11%)
            • Palmar-plantar erythrodysesthesia, Grade 2-4 (11%)

            Platinum-sensitive

            • Fatigue (82%)
            • Nausea (72%)
            • Thrombocytopenia (58%)
            • Epistaxis (55%)
            • Headache (49%)
            • Hypertension (42%)
            • Diarrhea (38-39%)
            • Decreased appetite (35%)
            • Abdominal pain, stomatitis, vomiting (33%)
            • Hyperglycemia (31%)
            • Dyspnea (30%)
            • Arthralgia (28%)
            • Hypomagnesemia (27%)
            • Cough (26%)
            • Insomnia, back pain (21%)

            >10% (Metastatic Renal Cell Carcinoma)

            Decreased appetite (36%)

            Fatigue (33%)

            Hypertension (28%)

            Epistaxis (27%)

            Headache (24%)

            Diarrhea (21%)

            Decreased weight (20%)

            Proteinuria (20%)

            Myalgia (19%)

            Back pain (12%)

            >10% (Metastatic Colorectal Cancer)

            Leukopenia (37%)

            Diarrhea (34%)

            Neutropenia (21%)

            Hypertension (12%)

            1-10% (Epithelial ovarian, fallopian tube or primary peritoneal cancer)

            Treatment following resection

            • Nasal mucosal disorder (7-10%)

            Platinum resistant

            • Epistaxis (5%)

            Platinum-sensitive

            • Rhinorrhea (10%)
            • Hyperkalemia (9%)
            • Hemorrhoids (8%)
            • Sinus congestion (8%)
            • Gingival bleeding (7%)

            1-10% (Metastatic Colorectal Cancer)

            Asthenia (10%)

            Deep vein thrombosis (9%)

            Abdominal pain (8%)

            Pain (8%)

            Constipation (4%)

            Intra-abdominal thrombosis (3%)

            Syncope (3%)

            1-10% (Metastatic Renal Cell Carcinoma)

            Dysphonia (5%)

            Postmarketing Reports

            Body as whole: Polyserositis

            Cardiovascular: Pulmonary hypertension, RPLS, mesenteric venous occlusion

            Osteonecrosis of the jaw

            Eye disorders (from unapproved intravitreal use for treatment of various ocular disorders): Permanent loss of vision, endophthalmitis (infectious and sterile), intraocular inflammation, retinal detachment, increased IOP, hemorrhage (including conjunctival, vitreous hemorrhage, or retinal hemorrhage), vitreous floaters, ocular hyperemia, ocular pain or discomfort

            Gastrointestinal: Gastrointestinal ulcer, intestinal necrosis, anastomotic ulceration

            Hemic and lymphatic: Pancytopenia

            Hepatobiliary disorders: Gallbladder perforation

            Infections and infestations: Necrotizing fasciitis, usually secondary to wound healing complications, gastrointestinal perforation or fistula formation

            Musculoskeletal: Osteonecrosis of the jaw

            Renal: Renal thrombotic microangiopathy

            Respiratory: Nasal septum perforation

            Dysphonia

            Persistent, recurrent, or metastatic carcinoma of the cervix

            Systemic events (from unapproved intravitreal use for treatment of various ocular disorders): Arterial thromboembolic events, hypertension, gastrointestinal perforation, hemorrhage

            Non-mandibular osteonecrosis and posterior reversible encephalopathy syndrome (PRES)

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            Warnings

            Black Box Warnings

            Gastrointestinal perforations

            • The incidence of gastrointestinal perforation, some fatal, ranges from 0.3-3%
            • Typical presentation reported as abdominal pain associated with symptoms such as constipation and vomiting
            • Include GI perforation in the differential diagnosis of patients presenting with abdominal pain
            • Discontinue therapy in patients with GI perforation

            Surgery and wound healing complications

            • Administration may result in the development of fatal wound dehiscence
            • Discontinue therapy in patients with wound dehiscence requiring medical intervention
            • Withhold at least 28 days prior to elective surgery
            • Do not initiate bevacizumab for at least 28 days after surgery and until the surgical wound is fully healed

            Hemorrhage

            • Severe or fatal hemorrhage, hemoptysis, gastrointestinal bleeding, hematemesis, CNS hemorrhage, and vaginal bleeding are increased in bevacizumab-treated patients
            • Do not administer the drug to patients with serious hemorrhage or recent hemoptysis; discontinue in patients who develop Grade 3-4 hemorrhage

            Contraindications

            None

            Cautions

            See also Dosage Modifications

            Impairs wound healing; discontinue before elected surgeries and do not initiate following surgery (see Black Box Warnings)

            Bevacizumab products can result in minor hemorrhage, most commonly Grade 1 epistaxis; and serious, and in some cases fatal, hemorrhagic events (see Black Box Warnings)

            Serious, sometimes fatal, arterial thromboembolic events (ATE) including cerebral infarction, transient ischemic attacks, myocardial infarction, angina, and a variety of other ATE; discontinue bevacizumab for severe ATE

            Increased risk of venous thromboembolic events (VTE) reported in patients treated with bevacizumab for cervical cancer; discontinue bevacizumab for life-threatening VTE

            Monitor blood pressure and treat hypertension; increased risk for severe hypertension; temporarily suspend treatment; discontinue if hypertensive crisis or hypertensive encephalopathy

            Increased relative risk for heart failure has been associated with therapy

            Posterior reversible encephalopathy syndrome (PRES) reported (0.5%); discontinue if PRES develops

            Proteinuria reported; temporarily suspend treatment for ≥2 g proteinuria/24 hr; discontinue if nephrotic syndrome occurs (incidence <1%)

            Risk of ovarian failure reported especially in premenopausal women receiving bevacizumab in combination with mFOLFOX chemotherapy compared to mFOLFOX alone; inform females of reproductive potential of the risk of ovarian failure prior to starting treatment

            Advise females of reproductive potential to use effective contraception during treatment with and for 6 months after the last dose (see Pregnancy)

            Infusion reactions may occur and include hypertension, hypertensive crises associated with neurologic signs and symptoms, wheezing, oxygen desaturation, Grade 3 hypersensitivity, chest pain, headaches, rigors, and diaphoresis; stop infusion if severe and administer appropriate therapy

            Bevacizumab is not indicated for use with anthracycline-based chemotherapy; incidence of Grade≥3 left ventricular dysfunction was 1% in patients receiving bevacizumab compared to 0.6% of patients receiving chemotherapy alone (see Dosage Modifications)F

            GI perforation and fistula formation

            • Serious and sometimes fatal GI perforation occurs
            • Serious and sometimes fatal fistula formation involving tracheo-esophageal, bronchopleural, biliary, vaginal, renal and bladder sites occurs at a higher incidence in bevacizumab-treated patients compared to controls
            • Avoid in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
            • Also see Black Box Warnings and Dosage Modifications
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            Pregnancy & Lactation

            Pregnancy

            Bevacizumab products may cause fetal harm based on findings from animal studies and mechanism of action; limited postmarketing reports describe cases of fetal malformations with bevacizumab use in pregnancy; however, these reports are insufficient to determine drug associated risks

            Animal data

            • In animal reproduction studies, IV administration of bevacizumab to pregnant rabbits every 3 days during organogenesis at doses ~1-10 times the clinical dose of 10 mg/kg produced fetal resorptions, decreased maternal and fetal weight gain and multiple congenital malformations including corneal opacities and abnormal ossification of the skull and skeleton including limb and phalangeal defects
            • Animal models link angiogenesis and VEGF and VEGF Receptor 2 (VEGFR2) to critical aspects of female reproduction, embryofetal development, and postnatal development

            Contraception

            • Advise pregnant women of the potential risk to a fetus
            • Advise female patients of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of bevacizumab

            Infertility

            • Inform females of reproductive potential of the risk of ovarian failure prior to starting; long term effects of bevacizumab exposure on fertility are unknown

            Lactation

            Unknown if excreted in breast milk; discontinuation of nursing advised during & for a prolonged period following use (due to the long half-life)

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Recombinant humanized monoclonal antibody to VEGF; blocks the angiogenic molecule VEGF thereby inhibiting tumor angiogenesis, starving tumor of blood and nutrients

            Absorption

            Based on a population pharmacokinetic analysis of 491 patients who received bevacizumab 1-20 mg/kg weekly, q2Weeks, or q3Weeks, bevacizumab pharmacokinetics are linear and predicted time to reach >90% of steady state concentration is 84 days

            Distribution

            Vd: 2.9 L (mean); 3.2 L (males); 2.7 L (females)

            Elimination

            Clearance: 0.23 L/day (mean); 0.26 L/day (males); 0.21 L/day (women)

            Half-life: 20 days

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            Administration

            IV Compatibilities

            0.9% NaCl

            IV Incompatibilities

            D5W or any dextrose-containing solution

            IV Preparation

            Visually inspect for particulate matter and discoloration prior to administration

            Do not use vial if solution is cloudy, discolored, or contains particulate matter

            Aseptically withdraw necessary amount & dilute in a total volume of 100 mL NS

            Diluted solutions for infusion may be stored at 2-8°C for 8 hr

            Do not shake vials or diluted solutions

            IV Administration

            IV infusion only

            First infusion: Infuse over 90 minutes

            Subsequent infusions: Infuse second infusion over 60 minutes if first infusion is tolerated; infuse all subsequent infusions over 30 minutes if second infusion over 60 minutes is tolerated

            Do not administer as IV push or bolus; administer only as an IV infusion

            Do not initiate until at least 28 days following major surgery; wait until the surgical incision has fully healed

            Storage

            Do not freeze

            Protect vials from light

            Unused vials: Refrigerate at 2-8°C (36-46°F)

            Diluted solutions: Refrigerate at 2-8°C (36-46°F) for up to 8 hours

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            Images

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.