AVASTIN(Bevacizumab)英文说明书

U.S. BLA Amendment: Bevacizumab—Genentech, Inc.
1 of 27: GNE_clean_PI_Feb_13
1.14.1.3 Labeling Text 1
AVASTIN™ 2
(Bevacizumab) 3
For Intravenous Use 4
WARNINGS 5
Gastrointestinal Perforations/Wound Healing Complications 6
AVASTIN administration can result in the development of gastrointestinal 7
perforation and wound dehiscence, in some instances resulting in fatality. 8
Gastrointestinal perforation, sometimes associated with intra-abdominal 9
abscess, occurred throughout treatment with AVASTIN (i.e., was not 10
correlated to duration of exposure). The incidence of gastrointestinal 11
perforation in patients receiving bolus-IFL with AVASTIN was 2%. The 12
typical presentation was reported as abdominal pain associated with 13
symptoms such as constipation and vomiting. Gastrointestinal perforation 14
should be included in the differential diagnosis of patients presenting with 15
abdominal pain on AVASTIN. AVASTIN therapy should be permanently 16
discontinued in patients with gastrointestinal perforation or wound 17
dehiscence requiring medical intervention. The appropriate interval 18
between termination of AVASTIN and subsequent elective surgery 19
required to avoid the risks of impaired wound healing/wound dehiscence 20
has not been determined. (See WARNINGS: Gastrointestinal 21
Perforations/Wound Healing Complications and DOSAGE AND 22
ADMINISTRATION: Dose Modifications.) 23
Hemorrhage 24
Serious, and in some cases fatal, hemoptysis has occurred in patients with 25
non–small cell lung cancer treated with chemotherapy and AVASTIN. In 26
a small study, the incidence of serious or fatal hemoptysis was 31% in 27
patients with squamous histology and 4% in patients with adenocarcinoma 28
receiving AVASTIN as compared to no cases in patients treated with 29
chemotherapy alone. Patients with recent hemoptysis should not receive 30
AVASTIN. (See WARNINGS: Hemorrhage and DOSAGE AND 31
ADMINISTRATION: Dose Modifications .) 32
U.S. BLA Amendment: Bevacizumab—Genentech, Inc.
2 of 27: GNE_clean_PI_Feb_13
DESCRIPTION 33
AVASTINä (Bevacizumab) is a recombinant humanized monoclonal 34
IgG1 antibody that binds to and inhibits the biologic activity of human 35
vascular endothelial growth factor (VEGF) in in vitro and in vivo assay 36
systems. Bevacizumab contains human framework regions and the 37
complementarity-determining regions of a murine antibody that binds to 38
VEGF (1). Bevacizumab is produced in a Chinese Hamster Ovary 39
mammalian cell expression system in a nutrient medium containing the 40
antibiotic gentamicin and has a molecular weight of approximately 41
149 kilodaltons. AVASTIN is a clear to slightly opalescent, colorless to 42
pale brown, sterile, pH 6.2 solution for intravenous (IV) infusion. 43
AVASTIN is supplied in 100 mg and 400 mg preservative- free, single- use 44
vials to deliver 4 mL or 16 mL of AVASTIN (25 mg/mL). The 100 mg 45
product is formulated in 240 mg a,a-trehalose dihydrate, 23.2 mg sodium 46
phosphate (monobasic, monohydrate), 4.8 mg sodium phosphate (dibasic, 47
anhydrous), 1.6 mg polysorbate 20, and Water for Injection, USP. The 48
400 mg product is formulated in 960 mg a,a-trehalose dihydrate, 92.8 mg 49
sodium phosphate (monobasic, monohydrate), 19.2 mg sodium phosphate 50
(dibasic, anhydrous), 6.4 mg polysorbate 20, and Water for Injection, 51
USP. 52
CLINICAL PHARMACOLOGY 53
Mechanism of Action 54
Bevacizumab binds VEGF and prevents the interaction of VEGF to its 55
receptors (Flt-1 and KDR) on the surface of endothelial cells. The 56
interaction of VEGF with its receptors leads to endothelial cell 57
proliferation and new blood vessel formation in in vitro models of 58
angiogenesis. Administration of Bevacizumab to xenotransplant models 59
of colon cancer in nude (athymic) mice caused reduction of microvascular 60
growth and inhibition of metastatic disease progression. 61
Pharmacokinetics 62
The pharmacokinetic profile of Bevacizumab was assessed using an assay 63
that measures total serum Bevacizumab concentrations (i.e., the assay