bevacizumab

bevacizumab,

a DNA-derived monoclonal antibody that selectively binds to and inhibits activity of human vascular endothelial growth factor to reduce microvascular growth and inhibition of metastatic disease progression.

indications This drug is used to treat metastatic carcinoma of the colon or rectum in combination with 5-FU IV. It is also being investigated for use as an adjunctive in breast and renal cancer.

contraindications Known hypersensitivity to this drug prohibits its use.

adverse effects Adverse effects of this drug include hypertension, hypotension, nausea, vomiting, anorexia, diarrhea, constipation, abdominal pain, anorexia, colitis, stomatitis, proteinuria, urinary frequency and urgency, bilirubinemia, hypokalemia, dyspnea, and upper respiratory tract infection. Life-threatening side effects include deep vein thrombosis, hypertensive crisis, GI hemorrhage, nephritic syndrome, leukopenia, neutropenia, thrombocytopenia, exfoliative dermatitis, and hemorrhage. Common side effects include asthenia and dizziness.

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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.

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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.

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bevacizumab Warning - High-alert drug!

Avastin

Pharmacologic class: Monoclonal antibody

Therapeutic class: Immunologic agent

Pregnancy risk category C

FDA Boxed 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 microvascular 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-based chemotherapy)

Adults: 5 mg/kg I.V. infusion q 14 days until disease progression occurs

Contraindications

None

Precautions

Use cautiously in:
• hypersensitivity to drug
• cardiovascular disease
• development of immunogenicity
• patients sensitive to infusion reactions
• patients recovering from major surgery
• elderly patients
• pregnant or breastfeeding patients
• children.

Administration

• Withdraw necessary amount for 5 mg/kg 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 hypertensive crisis, severe bleeding, abdominal pain (may signal intra-abdominal abscess or GI perforation), wound dehiscence, or urinary problems.
• Know that drug is given in combination with 5-fluorouracil-based chemotherapy.
• 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.

Route	Onset	Peak	Duration
I.V.	Unknown	Unknown	Unknown

Adverse reactions

CNS: asthenia, dizziness, headache, confusion, syncope, abnormal gait

CV: hypotension, hypertension, hypertensive crisis, heart failure, deep-vein thrombosis, intra-abdominal thrombosis, thromboembolism

EENT: excess lacrimation, severe epistaxis

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

GU: proteinuria, urinary frequency or urgency, nephrotic syndrome

Hematologic: leukopenia, neutropenia, hemorrhage

Hepatic: bilirubinemia

Metabolic: hypokalemia

Musculoskeletal: myalgia

Respiratory: upper respiratory tract infection, dyspnea, massive hemoptysis

Skin: exfoliative dermatitis, alopecia, dry skin, skin discoloration, skin ulcers, nail disorder, wound-healing complications, wound dehiscence

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

Interactions

Drug-drug . Irinotecan: increased concentration of irinotecan metabolite

Drug-diagnostic tests. Leukocytes, potassium: decreased levels

Urine protein: increased level

Patient monitoring

☞ Monitor patient closely for signs and symptoms of thromboembolism and GI perforation (such as abdominal pain, vomiting, and constipation).
☞ Stay alert for delayed wound healing and wound dehiscence.
• 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.
• 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.