bevacizumab


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bevacizumab

Avastin

Pharmacologic class: Monoclonal antibody

Therapeutic class: Immunologic agent

Pregnancy risk category C

FDA Box Warning

• Drug may cause GI perforation, in some cases leading to death. Include such perforation in differential diagnosis of patients who experience abdominal pain during therapy. Discontinue permanently in patients with GI perforation.

• Drug may lead to potentially fatal wound dehiscence. Discontinue permanently in patients with wound dehiscence requiring medical intervention.

• Serious and, in some cases fatal, hemoptysis has occurred in patients with non-small-cell lung cancer who received chemotherapy and bevacizumab. Don't give to patients with recent hemoptysis.

Action

Binds to vascular endothelial growth factor, preventing or reducing micro-vascular formation and growth and inhibiting metastatic disease progression

Availability

Solution for injection: 25 mg/ml in 4-ml and 16-ml vials

Indications and dosages

First-line treatment of metastatic cancer of colon or rectum (used in combination with 5-fluorouracil [5-FU]-based chemotherapy)

Adults: 5 mg/kg I.V. infusion q 14 days until disease progression occurs when used with 5-FU, irinotecan, and leucovorin or 10 mg/kg I.V. infusion q 14 days until disease progression occurs when used with 5-FU, oxaliplatin, and leucovorin

Unresectable, locally advanced, recurrent or metastatic nonsquamous, non-small-cell lung cancer

Adults: 15 mg/kg I.V. infusion q 3 weeks

Contraindications

None

Precautions

Use cautiously in:

• hypersensitivity to drug

• cardiovascular disease

• development of immunogenicity

• patients sensitive to infusion reactions

• patients recovering from major surgery, nongastrointestinal fistula

• recent history of hemoptysis (Don't administer drug.)

• patients with proteinuria

• elderly patients

• pregnant or breastfeeding patients

• children.

Administration

• Withdraw necessary amount to obtain required dose, and dilute in 100 ml of 0.9% sodium chloride injection.

Don't mix or administer drug with dextrose solutions.

Don't deliver by I.V. push or bolus.

• Initially, infuse drug over 90 minutes. If patient tolerates infusion well, infuse over 60 minutes the second time; if he continues to tolerate it well, infuse each dose over 30 minutes thereafter.

Withhold dose if hypertension occurs.

Stop infusion if patient develops infusion reaction, hypertensive crisis, severe bleeding, abdominal pain (may signal intra-abdominal abscess or GI perforation), wound dehiscence, or urinary problems.

• Be aware that drug shouldn't be given within 28 days after major surgery and that therapy should be suspended several weeks before elective surgery.

Adverse reactions

CNS: asthenia, dizziness, headache, confusion, syncope, abnormal gait, transient ischemia attack, reversible leukoencephalopathy syndrome, cerebral infarction

CV: hypotension, hypertension, angina, hypertensive crisis, heart failure, deep-vein thrombosis, intraabdominal thrombosis, thromboembolism, MI

EENT: excess lacrimation, visual disturbances, rhinitis, severe epistaxis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, stomatitis, dyspepsia, flatulence, colitis, dry mouth, anorexia, GI perforation, intra-abdominal abscess, rectal hemorrhage

GU: proteinuria, urinary frequency or urgency, nephrotic syndrome

Hematologic: leukopenia, neutropenia, hemorrhage

Hepatic: bilirubinemia

Metabolic: hypokalemia, hyponatremia

Musculoskeletal: myalgia, back pain

Respiratory: upper respiratory tract infection, dyspnea, massive hemoptysis

Skin: wound-healing complications, dry skin, exfoliative dermatitis, wound dehiscence

Other: abnormal taste, altered voice, pain, weight loss, infusion reaction

Interactions

Drug-drug. Irinotecan: increased concentration of irinotecan metabolite

Drug-diagnostic tests. Leukocytes, potassium, sodium: decreased levels Urine protein: increased level

Patient monitoring

Monitor patient closely and discontinue drug if signs and symptoms of thromboembolism and GI perforation (such as abdominal pain, vomiting, and constipation), serious bleeding, nephrotic syndrome, or hypertensive crisis develops.

Stay alert for and discontinue drug if nongastrointestinal fistula formation, delayed wound healing, or wound dehiscence requiring medical intervention occurs.

Stay alert for and discontinue drug if signs and symptoms of leukoencephalopathy occur (such as headache, seizures, lethargy, confusion, or blindness).

• Assess blood pressure frequently.

• Monitor CBC with differential and urine protein and serum electrolyte levels.

Patient teaching

Tell patient to call prescriber immediately if he experiences dizziness, severe bleeding, stomach pain, or urinary problems or if a wound opens.

• Instruct patient to tell prescriber if he has been exposed to chickenpox or if he has gout, heart disease, viral infection, urinary problems, hepatic disease, or another form of cancer.

• Advise patient to tell prescriber if he has surgery planned; drug may delay wound healing.

• Caution patient not to get immunizations unless prescriber approves.

• Inform female patients of childbearing potential risk of ovarian failure before starting drug.

• Instruct female patient to tell prescriber if she is pregnant, plans to become pregnant, or is breast-feeding.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

bevacizumab

(bĕv′ə-sĭz′ə-măb′)
n.
A humanized monoclonal antibody that acts as an angiogenesis inhibitor, used intravenously to treat metastatic colorectal cancer and certain other types of cancer.

bevacizumab

A humanised monoclonal antibody which inhibits vascular endothelial growth factor (VEGF) which has anti-angiogenic effects, and is used to treat colorectal, lung and kidney cancers, as well as glioblastomas. It is not FDA-approved for managing breast cancer.

Adverse effects
Hypertension, haemorrhage.

bevacizumab

The first anti-angiogenesis drug to be shown effective in treating metastatic cancer. Bevacizumab is a recombinant humanized monoclonal antibody that attacks the protein that promotes growth of blood vessels, the vascular endothelial growth factor). Used in combination with standard anticancer chemotherapy the drug shrinks tumours and extends the life of affected patients. The drug has also been used in the treatment of age-related neovascular macular degeneration.

anti-VEGF drugs 

Drugs which bind to VEGF receptors without causing activation, thus blocking the production of new blood vessels and enhanced vessel permeability by the vascular endothelial growth factor (VEGF). They are used in the treatment of some forms of cancer (administered intravenously), and injected intravitreally in the treatment of choroidal neovascularization, retinal venous occlusion, and macular oedema. Examples: bevacizumab, pegaptanib sodium, ranibizumab. Syn. angiogenesis inhibitors. See age-related macular degeneration; diabetic retinopathy; VEGF.

macular degeneration, age-related (ARMD, AMD)

A common, chronic degenerative condition found in a large percentage of elderly patients (and sometimes middle-aged ones) characterized by loss of central vision. There are two main forms of the condition: non-neovascular (dry, atrophic) AMD, which is the most common, and exudative (wet, neovascular) AMD in which the loss of vision is the most severe. The main features of dry AMD are the presence in the macular region of small, yellowish-white spots (hard drusen) and large, poorly defined, coalescing soft drusen, focal hyperpigmentation of the retinal pigment epithelium (RPE) and at a later stage geographic atrophy of the RPE and depigmentation exposing choroidal vessels. Visual acuity becomes markedly reduced, there is metamorphopsia and the condition usually becomes bilateral over several years. The condition is managed essentially by the use of low vision aids.Exudative AMD has a similar clinical picture initially but is followed by choroidal neovascularization (CNV), which gives rise to subretinal fluid, haemorrhages, exudation, RPE detachment and subretinal fibrosis in the macular region resulting in severe loss of central vision. If detected early (usually with an Amsler chart), treatment with laser photocoagulation will reduce the risk of further visual loss. Photodynamic therapy (PDT) is another method of reducing the risk of visual loss. It allows selective destruction of the choroidal neovascularization with minimal damage to the overlying retinal tissue. It consists of injecting a photosensitizing agent (e.g. verteporfin) that is taken up by the abnormal vessels and when activated by a laser light of a given wavelength (e.g. 689 nm) it damages and shrivels up the vessels. Recent drug therapies, such as the anti-VEGF ranibizumab and bevacizumab, which are injected intravitreally at regular intervals and designed to stop the leakage and the growth of blood vessels, not only reduce loss of vision but improve visual acuity in a significant percentage of cases of wet AMD. Syn. senile macular degeneration. See fluorescein angiography; disciform scar; drusen; macular dystrophy; lipofuscin; age-related maculopathy; oxidative stress; macular pigment; Kollner's rule; photostress test; VEGF.
References in periodicals archive ?
Intravitreal injection of bevacizumab alone or with triamcinolone acetonide for treatment of macular edema caused by central retinal vein occlusion.
From February 2012 to November 2012, 10 patients with severe brain edema were treated with bevacizumab. The patients' characteristics are shown in [Table 1].{Table 1}
Cases were defined as acute endophthalmitis occurring among patients [less than or equal to] 14 days after they received intraocular injection with bevacizumab that had been repackaged at pharmacy A after December 18, 2012.
ONS-5010 is an ophthalmic formulation of bevacizumab to be administered as an intravitreal injection for the treatment of wet AMD and other retina diseases.
The trial met its primary endpoint in the intent-to-treat population with a statistically-significant and clinically-meaningful improvement in progression-free survival, increasing the time women taking Lynparza plus bevacizumab lived without disease progression or death vs.
The late-stage study, called PAOLA-1, assessed Lynparza plus bevacizumab in the first line maintenance setting in comparison to bevacizumab alone in women with advanced ovarian cancer, irrespective of BRCA gene mutations.
Informed consent for use of Bevacizumab as offlabel drug was obtained from all patients prior to this prospective clinical trial.
Bevacizumab, which is marketed under the trade name Avastin in China, has been approved globally for the treatment of multiple types of malignant tumors including NSCLC.
In comparison of phase-contrast appearance of RPE culture cells 72 hours after supplementation with aflibercept (0.5 mg/mL), bevacizumab (0.3125 mg/mL), and ranibizumab (0.125 mg/mL), and control culture, phase contrast images showed no morphological changes in the RPE culture cells with any drug and RPE cells maintained their hexagonal morphology (Figure 1).
Conclusion: Intravitreal Bevacizumab injection, given monthly in patients of ED results in significantly more regression in neovascularization, and less requirement for PPV, as compared to those receiving standard steroids and laser photocoagulation treatment.
Nevertheless, up to now, only a few studies combined bevacizumab, gefitinib and WBRT for treating BM from NSCLC.