title: Safety of Perflutren Ultrasound Contrast Agents: A Disproportionality Analysis of the US FAERS Database.
abstract: BACKGROUND
  Perflutren microbubble/microsphere ultrasound contrast agents have a black-box warning based on case reports of serious cardiopulmonary events. There have been several subsequent observational safety studies. Large spontaneous reporting databases may help detect/refine signals of rare adverse events that elude other data sources/study designs.
  
  
  OBJECTIVE
  The objective of this study was to supplement existing knowledge of the reported safety of perflutren using statistical analysis of spontaneous reports.
  
  
  METHODS
  We analyzed information from the US Food and Drug Administration Adverse Event Reporting System using a disproportionality analysis. Analysis of overall reporting for perflutren was supplemented by subset (age, indication) analysis. A signal of disproportionate reporting (SDR) was defined as EB05 >2.
  
  
  RESULTS
  Overall, 18/380 Preferred Terms and 1/83 Standardized Medical Queries had SDRs. Most were small (EB05 = 2-4). Back pain and flank pain were the largest SDRs followed by events compatible with signs/symptoms of hypersensitivity. The general pattern of SDRs in the subset analysis was consistent with the overall analysis. Almost all events with SDRs were literally or conceptually labeled. Except for chest pain (higher in the age <65 years subgroup) and back pain (higher in the age ≥65 years subgroup), there were no statistically significant differences between age subsets. Except for the Preferred Terms Pruritus and Urticaria and the narrow Standardized Medical Queries Ventricular tachyarrhythmia, Angioedema, Oropharyngeal allergic conditions, and Hypersensitivity (higher in the stress test subgroup), there were no statistically significant reporting differences between indication subsets. There were no SDRs associated with the major cardiovascular events of death, myocardial infarction/ischemia, angina, arrhythmias, or convulsions in any analysis.
  
  
  CONCLUSIONS
  Our combined signal detection/evaluation analysis did not identify SDRs of novel adverse events or major cardiovascular events associated with perflutren ultrasound contrast agents. The negative results for major cardiovascular events extend previous signal evaluation exercises supporting the relative cardiovascular safety of these agents.
authors.affiliation: New York University Medical Center, New York, NY, USA.|Pfizer, Incorporated, 219 East 42nd Street, New York, NY, 10017, USA.
authors.forename: Manfred
authors.initials: M
authors.lastname: Hauben
authors.affiliation: Pfizer, Incorporated, 219 East 42nd Street, New York, NY, 10017, USA. eric.hung@pfizer.com.
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Hung
authors.affiliation: Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Kelly C
authors.initials: KC
authors.lastname: Hanretta
authors.affiliation: New York University Medical Center, New York, NY, USA.
authors.forename: Sripal
authors.initials: S
authors.lastname: Bangalore
authors.affiliation: Pfizer, Incorporated, 219 East 42nd Street, New York, NY, 10017, USA.
authors.forename: Vincenza
authors.initials: V
authors.lastname: Snow
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems / Q000592:standards / Q000706:statistics & numerical data*; D000368:Aged; D003287:Contrast Media / Q000009:adverse effects*; D016208:Databases, Factual / Q000592:standards / Q000706:statistics & numerical data*; D005260:Female; D005466:Fluorocarbons / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D003287:Contrast Media; D005466:Fluorocarbons; C042852:perflutren