bevacizumab (Avastin)
Classes: Antineoplastics, Monoclonal Antibody; Antineoplastics, VEGF Inhibitor
Dosing and uses of Avastin (bevacizumab)
Adult dosage forms and strengths
injectable solution
- 25mg/mL
Metastatic Colorectal Cancer
Indicated for first-line and second-line treatment for metastatic colorectal carcinoma (in combination with 5-fluorouracil-based chemotherapy)
Fluorouracil based chemotherapy: 5-10 mg/kg IV q2Weeks
Administer 5 mg/kg when used in combination with bolus-IFL (ie, irinotecan, 5-FU, leucovorin)
Administer 10 mg/kg when used in combination with FOLFOX4 (ie, oxaliplatin, 5-FU, leucovorin)
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
Nonsmall Cell Lung Cancer
Indicated for unresectable, locally advanced, recurrent or metastatic, nonsquamous NSCLC in combination wtih carboplatin and paclitaxeL
15 mg/kg IV q3wk
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
Indicated for metastatic renal cell carcinoma (with interferon alfa-2a)
10 mg/kg IV q2Weeks (with interferon alfa-2a or as monotherapy)
Cervical Cancer
Indicated as part of a combination chemotherapy regimen for persistent, recurrent, or metastatic carcinoma of the cervix
15 mg/kg IV infusion q3wk
Administer in combination with 1 of the following chemotherapy regimens: paclitaxel and cisplatin, or paclitaxel and topotecan
Ovarian, Fallopian Tube, or Peritoneal Cancer
Indicated in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan is indicated for the treatment of patients with platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who received no more than 2 prior chemotherapy regimens
10 mg/kg IV q2Weeks in combination with 1 of the following IV chemotherapy regimens: paclitaxel, pegylated liposomal doxorubicin, or topotecan (weekly) Or
15 mg/kg IV q3Weeks in combination with topotecan (q3Weeks)
Glioblastoma
Indicated for glioblastoma as a single agent for patients with progressive disease following prior therapy
10 mg/kg IV q2wk
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
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)
Pediatric dosage forms and strengths
Safety and efficacy not established
Avastin (bevacizumab) adverse (side) effects
>10%
Weakness (73-74%)
Hypertension (23-67%; grades 3/4: 8-18%)
Pain (61-62%)
Abdominal pain (50-61%; grades 3/4: 8%)
Vomiting (47-52%, grades 3/4:6-11%)
URI (40-47%)
Constipation (29-40%)
Leukopenia (grades 3/4: 37%)
Proteinuria (36%, grades 3/4: 3%)
Epistaxis (32-35%)
Ovarian failure (with mFolfox) (34%)
Diarrhea (grades 3/4: 2-34%)
Stomatitis (30-32%)
Alopecia (6-32%)
Neutropenia (grades 3/4: 6-27%)
Headache (26%; grades 3/4: 2-4%)
Dyspnea (25-26%)
Dizziness (19-26%)
GI hemorrhage (19-24%)
Dyspepsia (17-24%)
Taste alteration (14-21%)
Dry skin (7-20%)
Exfoliative dermatitis (3-19%)
Fatigue (grades 3/4: 5-19%)
Flatulence (11-19%)
Lacrimation disorder (6-18%)
Neuropathy (grades 3/4: 1-17%)
Weight loss (15-16%)
Hypokalemia (12-16%)
Skin discoloration (2-16%)
Thromboembolic events (grades 3/4: 15%)
Myalgia (8-15%)
Hypotension (7-15%)
Nausea (grades 3/4: 4-12%)
Back pain (undefined)
1-10%
Dehydration (grades 3/4: 3-10%)
DVT (6-9%; grades 3/4: 9%)
Polyuria (3-6%)
Bilirubinemia (1-6%)
Colitis (1-6%)
Confusion (1-6%)
Neutropenia (5%)
Thrombocytopenia (5%)
Xerostomia (4-7%)
Ileus (grades 3/4: 4-5%)
Abnormal gait (1-5%)
Bone pain (grade 3/4: 4%)
Hyponatremia (grades 3/4: 4%)
GI perforations (<4%)
Arterial thrombosis (3-4%)
Intra-abdominal venous thrombosis (grades 3/4: 3%)
Rash desquamation (grades 3/4: 3%)
Syncope (grades 3/4: 3%)
Infusion reaction (<3%)
Cardio-cerebrovascular arterial thrombotic event (2-4%)
CHF (2%)
Wound dehiscence (1%)
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
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)
Warnings
Black box warnings
Gastrointestinal perforations
- Gastrointestinal (GI) perforation, fistula formation, and/or intra-abdominal abscess unrelated to therapy duration reported in patients with colorectal cancer as well as other types of cancers
- 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 permanently 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
- Discontinue 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, CNS hemorrhage, and vaginal bleeding are increased in bevacizumab-treated patients
- Do not administer the drug to patients with serious hemorrhage or recent hemoptysis
Contraindications
None
Cautions
Impairs wound healing; discontinue before elected surgeries and do not initiate following surgery (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%)
Advise females of reproductive potential to use effective contraception during treatment with and for 6 months after the last dose
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
GI perforation and fistula formation
- Serious and sometimes fatal GI perforation occurs at a higher incidence in bevacizumab treated patients compared to controls; incidence of perforation ranged from 0.3 to 3.2% across clinical studies
- In a cervical cancer trial, the incidence of GI-vaginal fistulae was 8.2% in bevacizumab-treated patients and 0.9% in control patients, all of whom had a history of prior pelvic radiation
- In a platinum-resistant ovarian cancer trial, the incidence of GI perforation was 1.7%
- 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
- From a clinical trial in patients with persistent, recurrent, or metastatic cervical cancer, 1.8% of bevacizumab-treated patients and 1.4% of control patients were reported to have had nongastrointestinal vaginal, vesical, or female genital tract fistulae
Pregnancy and lactation
Pregnancy category: C
Lactation: not known 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.
Pharmacology of Avastin (bevacizumab)
Mechanism of action
Recombinant humanized monoclonal antibody to VEGF; blocks the angiogenic molecule VEGF thereby inhibiting tumor angiogenesis, starving tumor of blood and nutrients
Pharmacokinetics
Half-Life: 20 days (range 11-50 days)
Metabolism: N/A
Excretion: N/A
Administration
IV Preparation
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
IV Administration
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
Deliver first infusion over 90 min IV; if well-tolerated, second infusion may be administered over 60 min & each subsequent infusion, over 30 min if 60 min infusion tolerated
Storage
Refrigerate, do not freeze
Do not shake
Protect vials from light