Medication Guide App

Bevacizumab

Pronunciation

Pronunciation: BE-va-SIZ-ue-mab
Class: Monoclonal antibody

Trade Names

Avastin
- Injection, solution, concentrate 25 mg/mL

Pharmacology

Binds to vascular endothelial growth factor, interfering with endothelial cell proliferation.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

Time to reach steady state is predicted to be 100 days.

Elimination

Estimated half-life is approximately 20 days.

Special Populations

Children

Pharmacokinetic profile in pediatric patients has not been established.

Gender

Men had a higher Cl and larger Vd in the central compartment when compared with women. There is no evidence that this difference decreases the efficacy of bevacizumab in men.

Tumor burden

Patients with a higher tumor burden had a higher Cl of bevacizumab compared with patients who had a tumor burden below the median. There is no evidence suggesting that this difference leads to decreased efficacy.

Indications and Usage

In combination with IV 5–fluorouracil–based chemotherapy as first- or second-line treatment of metastatic carcinoma of the colon or rectum; in combination with carboplatin and paclitaxel as first-line treatment of unresectable, locally advanced, recurrent or metastatic nonsquamous non–small cell lung cancer; as single-agent therapy for glioblastoma with progressive disease following prior therapy; in combination with interferon alfa for the treatment of metastatic renal cell carcinoma.

Unlabeled Uses

Age-related macular degeneration; recurrent ovarian cancer.

Contraindications

None well documented.

Dosage and Administration

Glioblastoma
Adults

IV infusion 10 mg/kg every 14 days.

Metastatic Carcinoma of the Colon or Rectum
Adults

IV infusion 5 or 10 mg/kg every 14 days in combination with IV 5-fluorouracil–based chemotherapy. The recommended dosage is 5 mg/kg every 14 days when administered with irinotecan/5–fluorouracil/leucovorin, and 10 mg/kg every 14 days when administered with 5–fluorouracil/leucovorin/oxaliplatin (FOLFOX4).

Metastatic Renal Cell Carcinoma
Adults

IV infusion 10 mg/kg every 14 days in combination with interferon alfa.

Nonsquamous Non–Small Cell Lung Cancer
Adults

IV infusion 15 mg/kg every 21 days in combination with carboplatin and paclitaxel.

General Advice

  • For IV infusion only. Do not administer as an IV push or bolus.
  • Patients should continue treatment until disease progression or unacceptable toxicity.
  • For dilution, withdraw the necessary amount of bevacizumab and dilute in a total volume of 100 mL of sodium chloride 0.9% injection. Do not administer or mix with dextrose solutions.
  • Administer first dose via IV infusion over 90 min following chemotherapy. If the first infusion is well tolerated, the second infusion may be administered over 60 min. If the 60–min infusion is well tolerated, subsequent infusions may be administered over 30 min.
  • Discard any unused solution. Do not save for future administration.

Storage/Stability

Store vials in refrigerator (36° to 46°F) in original carton until time of use. Protect from light and freezing. Do not shake vials. Diluted solution for infusion may be refrigerated (36° to 46°F) for up to 8 h.

Drug Interactions

Irinotecan/5–fluorouracil/leucovorin

The incidence of epistaxis and grade 1 or 2 hemorrhage (including GI hemorrhage, minor gum bleeding, vaginal hemorrhage) was greater in patients receiving bevacizumab plus irinotecan/5-fluorouracil/leucovorin compared with patients receiving irinotecan/5-fluorouracil/leucovorin plus placebo. Closely monitor the patient during coadministration.

Live vaccines

The administration of live vaccines to patients receiving bevacizumab may result in a reduced immune response. Avoid coadministration.

Paclitaxel

Decreased paclitaxel exposure was seen when paclitaxel/carboplatin was given in combination with bevacizumab. Closely monitor the patient during coadministration.

Sunitinib

Coadministration of bevacizumab and sunitinib has been reported to cause unexpected severe toxicity (eg, microangiopathic hemolytic anemia). Coadministration of sunitinib and bevacizumab is not recommended.

Adverse Reactions

The following adverse reactions were reported with combined use of bevacizumab and 5-fluorouracil/leucovorin–, 5-fluorouracil/irinotecan/leucovorin–, 5-fluorouracil/leucovorin/oxaliplatin–, interferon alfa–, irinotecan–, paclitaxel–, or carboplatin/paclitaxel–based regimens.

Cardiovascular

Hypertension (34%); venous thromboembolic event (32%); hypotension (15%); deep vein thrombosis (9%); arterial thrombolic event (6%); CNS hemorrhage (5%); intra-abdominal thrombosis, syncope (3%).

CNS

Fatigue (45%); headache (37%); dizziness (26%); sensory neuropathy (17%); asthenia (10%); neurologic disorders (5%); reversible posterior leukoencephalopathy syndrome (1%).

Dermatologic

Alopecia (32%); skin ulcer, wound healing complications (6%).

EENT

Nasal septum perforation (postmarketing).

GI

Abdominal pain (61%); vomiting (52%); anorexia (43%); constipation (40%); diarrhea (34%); stomatitis (32%); dyspepsia, GI hemorrhage (24%); taste disorder (21%); nausea (12%); dry mouth (7%); colitis (6%); ileus (4%); GI perforation, gum bleeding (2%); anastomotic ulceration, GI ulcer, intestinal necrosis, mesenteric venous occlusion (postmarketing).

Genitourinary

Proteinuria (36%); vaginal hemorrhage (4%); renal thrombotic microangiopathy (manifested as severe proteinuria) (postmarketing).

Hematologic-Lymphatic

Bleeding/hemorrhage (40%); leukopenia (37%); neutropenia (27%); febrile neutropenia, thrombocytopenia (5%); infection with grade 3 or 4 neutropenia (4%); pancytopenia (postmarketing).

Metabolic-Nutritional

Weight loss (20%); dehydration (10%); hyponatremia (4%).

Musculoskeletal

Myalgia (19%); back pain (12%); osteonecrosis of the jaw (postmarketing).

Respiratory

Upper respiratory tract infection (47%); epistaxis (35%); dyspnea (26%); voice alteration (9%); dysphonia, pneumonitis/pulmonary infiltrates (5%); pulmonary hypertension (postmarketing).

Miscellaneous

Pain (62%); infection (55%); infection without neutropenia (7%); polyserositis (postmarketing).

Precautions

Warnings

GI perforation

Incidence of GI perforation, some fatal, ranges from 0.3% to 2.4%. Discontinue therapy in patients with GI perforation.

Hemorrhage

Severe or fatal hemorrhage, including hemoptysis, GI bleeding, CNS hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving bevacizumab. Do not administer bevacizumab to patients with serious hemorrhage or recent hemoptysis.

Surgery and wound healing complications

Increased incidence of wound healing and surgical complications, including serious and fatal complications, in bevacizumab-treated patients. Discontinue therapy in patients with wound dehiscence. Discontinue bevacizumab at least 28 days prior to elective surgery and do not initiate for at least 28 days after surgery and until the surgical wound is fully healed.


Monitor

Monitor patient for signs and symptoms of GI perforation (eg, abdominal pain in association with constipation and/or vomiting) or wound dehiscence. Monitor BP every 2 to 3 wk during therapy. Monitor for development or worsening of proteinuria with serial urinalyses.


Pregnancy

Category C .

Lactation

Undetermined, but human immunoglobulin G is excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Several studies indicate that patients 65 y and older may have a greater relative risk of adverse reactions (eg, emesis, ileus, nausea, proteinuria) compared with younger patients.

Arterial thrombotic events

Serious, sometimes fatal, arterial thrombotic events, including cerebral infarction, transient ischemic attacks, MI, and angina, have occurred. Permanently discontinue therapy in patients who experience a severe arterial thromboembolic event during therapy.

Congestive heart failure

Risk of developing CHF may be increased compared with administration of other chemotherapy alone. The safety of continuation or resumption of bevacizumab in patients with cardiac dysfunction has not been studied.

Hypertension

Temporarily suspend therapy in patients who develop severe hypertension that is not controlled with medical management. Permanently discontinue therapy in patients who develop hypertensive crisis or hypertensive encephalopathy.

Immunogenicity

May occur.

Infusion reactions

Interrupt therapy in cases of severe infusion reactions (eg, chest pain, hypertensive crisis).

Nephrotic syndrome

May occur. Discontinue bevacizumab in patients with nephrotic syndrome.

Neutropenia and infection

Incidences of neutropenia, febrile neutropenia, and infection were greater in patients receiving bevacizumab plus chemotherapy compared with chemotherapy alone.

Non-GI fistula formation

Biliary, bladder, bronchopleural, renal, tracheoesophageal, and vaginal fistula formation has been reported. Discontinue bevacizumab in patients with fistula formation involving an internal organ.

Ovarian failure

May occur; ovarian function recovered in some patients after treatment was discontinued.

Proteinuria

Risk of developing proteinuria may be increased. Temporarily suspend therapy in a patient who develops moderate to severe proteinuria, pending further evaluation.

Reversible posterior leukoencephalopathy syndrome

Has been reported and can present as blindness (and other visual disturbances), confusion, headache, lethargy, neurologic disturbances, and seizures.

Venous thromboembolic events

Incidence of venous thromboembolic events was greater in patients receiving bevacizumab plus chemotherapy compared with chemotherapy alone.

Overdosage

Symptoms

Severe headache.

Patient Information

  • Advise patients or caregivers that medication will be prepared and administered by a health care provider in a health care setting.
  • Advise patients or caregivers that medication will be administered in combination with other chemotherapy medications.
  • Advise patients, families, or caregivers to report any of the following to their health care provider: black or bloody stools; severe abdominal pain; severe constipation or vomiting; coughing up blood; high fever; injection-site reaction; problems with wound healing; rash, itching, or hives; severe nosebleeds; stomach pain in association with constipation and/or vomiting; swelling of the face, lips, eyes, or tongue; wheezing, shortness of breath, or difficulty breathing; or any other unusual or unexplained feelings or symptoms.
  • Advise patients to have routine BP monitoring and contact their health care provider if BP is elevated.
  • Advise women of childbearing potential to use effective contraception during and for at least 6 mo following treatment.
  • Inform patients of the increased risk of ovarian failure following treatment.
  • Advise patients of the increased risk of an arterial thromboembolic event and wound healing complications during and following treatment.

Copyright © 2009 Wolters Kluwer Health.

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