title: Safety of gadopentetate dimeglumine after 120 million administrations over 25 years of clinical use.
abstract: OBJECTIVE
  We evaluated the safety of gadopentetate dimeglumine (Gd-DTPA), the first contrast agent for magnetic resonance imaging, using pharmacovigilance data for spontaneously reported adverse events (AEs) after 120 million cumulative administrations worldwide.
  
  
  METHODS
  We analyzed spontaneously reported AEs for Gd-DTPA for pre-specified time periods between 1988 and 2011.
  
  
  RESULTS
  Since the market introduction of Gd-DTPA in 1988, its global utilization reached 120 million cumulative administrations in 2011, more than 80% of which was by the USA, countries in the European Union (EU), and Japan. The global AE reporting rate was 21.2 in 100,000 administrations in 1988 and 14.4 in 100,000 administrations by 2011. Regional differences included higher reporting rates in the USA and Japan, and reporting rates lower than global rates in the EU. The reported rate of global serious AEs changed from 1.4 in 100,000 administrations in 1988 to 4.0 in 100,000 administrations in 2011. The highest number of reports of nephrogenic systemic fibrosis (NSF) was received from 2006 to 2008. Since 2009, no report of a current onset of NSF has been received. The reduced report rate of NSF may be due to increased awareness about the use of gadolinium-based contrast agents (GBCAs).
  
  
  CONCLUSIONS
  After more than 120 million cumulative administrations, Gd-DTPA is a widely used GBCA that shows a consistently low and stable incidence of AEs.
authors.affiliation: Bayer Yakuhin Ltd., Medical Affairs Pharmacovigilance.
authors.forename: Toru
authors.initials: T
authors.lastname: Matsumura
authors.forename: Masakane
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Fumiki
authors.initials: F
authors.lastname: Shimada
authors.forename: Masahisa
authors.initials: M
authors.lastname: Yabuki
authors.forename: Susan
authors.initials: S
authors.lastname: Dohanish
authors.forename: Petra
authors.initials: P
authors.lastname: Palkowitsch
authors.forename: Kohki
authors.initials: K
authors.lastname: Yoshikawa
mesh_terms: D003287:Contrast Media / Q000009:adverse effects; D017723:Drug Utilization Review / Q000706:statistics & numerical data*; D005060:Europe; D019786:Gadolinium DTPA / Q000009:adverse effects*; D006801:Humans; D038622:Internationality; D007564:Japan; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D054989:Nephrogenic Fibrosing Dermopathy / Q000453:epidemiology* / Q000209:etiology*; D060735:Pharmacovigilance; D012042:Registries; D014481:United States
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA