PMID- 22612854
OWN - NLM
STAT- MEDLINE
DCOM- 20120814
LR  - 20220321
IS  - 1179-1942 (Electronic)
IS  - 0114-5916 (Linking)
VI  - 35
IP  - 6
DP  - 2012 Jun 1
TI  - Novel adverse events of bevacizumab in the US FDA adverse event reporting system 
      database: a disproportionality analysis.
PG  - 507-18
LID - 10.2165/11597600-000000000-00000 [doi]
AB  - BACKGROUND: Bevacizumab is the first in its class, vascular endothelial growth 
      factor (VEGF) inhibitor that was initially approved by the US FDA in 2004 for the 
      treatment of metastatic colon cancer and other solid tumors. Preapproval clinical 
      trials, particularly for oncology drugs, are limited in their ability to detect 
      certain adverse effects and, therefore, the FDA and pharmaceutical sponsors 
      collect and monitor reports of adverse events (AEs) following approval. 
      OBJECTIVE: The purpose of this study was to screen the FDA's Adverse Event 
      Reporting System (AERS) database for novel AEs that may be attributed to 
      bevacizumab. METHODS: The FDA AERS database was used to identify all AE reports 
      for bevacizumab from February 2004 to September 2009. Disproportionality analysis 
      was conducted for bevacizumab against all other drugs in the background by 
      setting statistical significance at proportional reporting ratio (PRR) >/=2, 
      observed case count >/=3 and chi-square >/=4. Subsequent clinical evaluation was 
      performed to determine the clinical relevance of the findings and to group 
      related events. RESULTS: A total of 523 Preferred Terms (PTs) were 
      disproportionally reported; following clinical review 63 (12%) were found to be 
      both unlabelled and of clinical importance. These PTs were grouped into 15 
      clinical disorder groups. Among the clinical disorders, electrolyte abnormalities 
      had the greatest number of reports (n = 426) followed by cardiovascular events 
      (n = 421), gastrointestinal events (n = 345), nervous system disorders (n = 106) 
      and pneumonitis (n = 96). On sensitivity analysis, a number of clinically 
      important unlabelled disorders, such as necrotizing fasciitis, vessel wall 
      disorders, arrhythmia and conduction disorder and autoimmune thrombocytopenia 
      still met the statistical significance criteria. CONCLUSIONS: During the study 
      period, out of 12 010 AE reports mentioning bevacizumab, it was listed as the 
      suspect drug in 94.2% of the reports. Our disproportionality analysis identified 
      many events that are already recognized as AEs of bevacizumab, but it also 
      identified a number of clinically important unlabelled terms, which if confirmed 
      in future studies would have potential implications for use of bevacizumab in 
      clinical practice.
FAU - Shamloo, Behrooz K
AU  - Shamloo BK
AD  - University of Nevada School of Medicine-Nevada Cancer Institute, Las Vegas, NV, 
      USA.
FAU - Chhabra, Pankdeep
AU  - Chhabra P
FAU - Freedman, Andrew N
AU  - Freedman AN
FAU - Potosky, Arnold
AU  - Potosky A
FAU - Malin, Jennifer
AU  - Malin J
FAU - Weiss Smith, Sheila
AU  - Weiss Smith S
LA  - eng
PT  - Journal Article
PL  - New Zealand
TA  - Drug Saf
JT  - Drug safety
JID - 9002928
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 2S9ZZM9Q9V (Bevacizumab)
SB  - IM
MH  - Adverse Drug Reaction Reporting Systems/*statistics & numerical data
MH  - Angiogenesis Inhibitors/*toxicity
MH  - Antibodies, Monoclonal, Humanized/*toxicity
MH  - Bevacizumab
MH  - *Databases, Factual
MH  - Humans
MH  - No-Observed-Adverse-Effect Level
MH  - United States
MH  - United States Food and Drug Administration
MH  - Vascular Endothelial Growth Factor A/antagonists & inhibitors
EDAT- 2012/05/23 06:00
MHDA- 2012/08/15 06:00
CRDT- 2012/05/23 06:00
PHST- 2012/05/23 06:00 [entrez]
PHST- 2012/05/23 06:00 [pubmed]
PHST- 2012/08/15 06:00 [medline]
AID - 6 [pii]
AID - 10.2165/11597600-000000000-00000 [doi]
PST - ppublish
SO  - Drug Saf. 2012 Jun 1;35(6):507-18. doi: 10.2165/11597600-000000000-00000.