Trade Names:Avastin- Injection, solution, concentrate 25 mg/mL
Binds to vascular endothelial growth factor, interfering with endothelial cell proliferation.
Time to reach steady state is predicted to be 100 days.
Estimated half-life is approximately 20 days.
Pharmacokinetic profile in children 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 a decreased efficacy.
In combination with IV 5–fluorouracil (5–FU)–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; in combination with paclitaxel for the treatment of patients who have not received chemotherapy for metastatic human epidermal growth factor receptor 2 (HER2)–negative breast 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.
In combination with erlotinib to treat metastatic renal cell carcinoma.
None well documented.
IV infusion 10 mg/kg every 14 days.Metastatic Breast CancerAdults
IV infusion 10 mg/kg every 14 days in combination with paclitaxel.Metastatic Carcinoma of the Colon or RectumAdults
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.Metastatic Renal Cell CarcinomaAdults
IV infusion 10 mg/kg every 14 days in combination with interferon alfa.Nonsquamous Non–Small Cell Lung CancerAdults
IV infusion 15 mg/kg every 21 days in combination with carboplatin and paclitaxel.
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.
Incidence of adverse events including hemorrhage, neutropenia and febrile neutropenia, venous thrombolic events, postoperative wound healing, or bleeding complications may be increased. Closely monitor the patient during 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 with the development of thrombocytopenia, anemia, reticulocytosis, decreased serum haptoglobin, and the presence of schistocytes). Coadministration of sunitinib and bevacizumab is not recommended.
None well documented.
The following adverse reactions were reported with combined use of bevacizumab and 5-FU/leucovorin–, 5-FU/irinotecan/leucovorin–, 5-FU/leucovorin/oxaliplatin–, capecitabine–, irinotecan–, paclitaxel–, or carboplatin/paclitaxel–based regimens.
Hypertension (34%); hypotension (15%); deep vein thrombosis (9%); venous thrombolic event (8%); arterial thrombolic event (6%); CNS hemorrhage, venous thrombus/embolism (5%); cerebrovascular ischemia, intra-abdominal thrombosis, syncope (3%); fatal MI.
Asthenia (57%); fatigue (45%); headache (37%); dizziness (26%); sensory neuropathy (24%); neurologic disorders (5%).
Exfoliative dermatitis (84%); alopecia (32%); skin ulcer, wound healing complications (6%); rash/desquamation (3%).
Nasal septum perforation (postmarketing).
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 (2%); anastomotic ulceration, intestinal necrosis, mesenteric venous occlusion (postmarketing); death caused by GI perforation.
Proteinuria (36%); albuminuria (22%); renal thrombotic microangiopathy (manifested as severe proteinuria) (postmarketing).
Bleeding/hemorrhage (40%); leukopenia (37%); neutropenia (27%); neutrophils (6%); febrile neutropenia, thrombocytopenia (5%); infection with grade 3 or 4 neutropenia (4%); pancytopenia (postmarketing).
Weight loss (20%); dehydration (10%); hyponatremia (4%).
Myalgia (19%); back pain (12%); bone pain (4%).
Upper respiratory tract infection (47%); epistaxis (35%); dyspnea (27%); voice alteration (9%); dysphonia, pneumonitis/pulmonary infiltrates (5%); pulmonary hypertension (postmarketing).
Pain (62%); infection without neutropenia (9%); infection with unknown absolute neutrophil count (3%); polyserositis, reversible posterior leukoencephalopathy syndrome (postmarketing); death associated with combined abdominal pain, diarrhea, hypotension, and weakness.
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 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.
Category C .
Undetermined, but human immunoglobulin G is excreted in breast milk.
Safety and efficacy not established.
Several studies indicate that patients 65 yr of age and older may have a greater relative risk for adverse reactions (eg, emesis, ileus, nausea, proteinuria) compared with younger patients.
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.
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.
Temporarily suspend treatment at least 4 wk prior to elective surgery.
Temporarily suspend therapy in patients who develop severe hypertension (more than 200/110 mm Hg) that is not controlled with medical management. Permanently discontinue therapy in patients who develop hypertensive crisis or hypertensive encephalopathy.
Interrupt therapy in cases of severe infusion reactions (eg, chest pain, hypertensive crisis).
May occur. Discontinue bevacizumab in patients with nephrotic syndrome.
Incidence of neutropenia, febrile neutropenia, and infection were greater in patients receiving bevacizumab plus chemotherapy compared with chemotherapy alone.
Biliary, bladder, bronchopleural, tracheoesophageal, and vaginal fistula formation has been reported. Discontinue bevacizumab in patients with fistula formation involving an internal organ.
Risk of developing proteinuria may be increased compared with administration of 5–fluorouracil alone. Temporarily suspend therapy in patient who develops moderate to severe proteinuria, pending further evaluation.
Has been reported and can present as blindness (and other visual disturbances), confusion, headache, lethargy, neurologic disturbances, and seizures.
Incidence of venous thromboembolic events and fatal arterial thromboembolic events was greater in patients receiving bevacizumab plus chemotherapy compared with chemotherapy alone.
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