title: Bevacizumab-induced serious side-effects: a review of the French pharmacovigilance database.
abstract: OBJECTIVE
  Bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor, is widely used in association with standard chemotherapy in metastatic cancer. Well tolerated, bevacizumab is sometimes associated with serious adverse drug reactions (ADRs). The objective of this study is to describe the profile of ADRs related to bevacizumab and reported to the French Pharmacovigilance system.
  
  
  METHODS
  All serious cases of ADRs associated with bevacizumab recorded in the French Pharmacovigilance database up to November 31, 2010 were identified and analyzed, focusing on patient information, drug exposure, and characteristics of the ADRs. Categorical variables were compared using the chi-square test when appropriate.
  
  
  RESULTS
  A total of 351 serious cases involving 626 ADRs were recorded in the database during the study interval. The most frequent ADRs reported involved the gastrointestinal system (21.9%). The most frequent ADRs included gastrointestinal perforation (4.8%), thromboembolic events (4.0%), pulmonary embolism (3.2%), hypertension (2.7%), gastrointestinal hemorrhage (2.7%), and cerebral hemorrhage or vascular accident (2.6%). The median duration of bevacizumab exposure was four cycles (range 1-30) when ADRs occurred. In 18 cases of death directly caused by ADRs, 50% occurred after only one cycle. In cases of disability, 40% of ADRs were neurologic: neuropathy, paralysis, and paresis.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first analysis of bevacizumab safety profile using data collected in a national pharmacovigilance database. Our study confirms the frequency and seriousness of gastrointestinal, thromboembolic, and hemorrhage events with bevacizumab use and provides a picture of the bevacizumab safety profile in daily medical practice, despite intrinsic limitations.
authors.affiliation: Hôpital Salvator, Assistance Publique des Hôpitaux de Marseille, Centre Régional de Pharmacovigilance, 249 Boulevard Sainte Marguerite, 13009 Marseille, France. solene.taugourdeau@ap-hm.fr
authors.forename: Solène
authors.initials: S
authors.lastname: Taugourdeau-Raymond
authors.forename: F
authors.initials: F
authors.lastname: Rouby
authors.forename: A
authors.initials: A
authors.lastname: Default
authors.forename: M-J
authors.initials: MJ
authors.lastname: Jean-Pastor
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000706:statistics & numerical data*; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000068258:Bevacizumab; D002648:Child; D002675:Child, Preschool; D016208:Databases, Factual; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D060735:Pharmacovigilance; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab