title: Emergency use authorization for intravenous peramivir: evaluation of safety in the treatment of hospitalized patients infected with 2009 H1N1 influenza A virus.
abstract: BACKGROUND
  On 23 October 2009, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for intravenous peramivir, an unapproved antiviral, to treat suspected or confirmed 2009 H1N1 influenza A virus infection. Eligible hospitalized patients were unresponsive to or unable to tolerate available antivirals or lacked dependable oral or inhaled drug delivery routes. The EUA required healthcare providers to report medication errors, selected adverse events (AEs), serious AEs, and deaths to the FDA.
  
  
  METHODS
  An FDA safety team analyzed reports submitted to the Adverse Event Reporting System (AERS) and sought follow-up in selected cases.
  
  
  RESULTS
  The FDA received AERS reports for 344 patients (including 28 children and 3 pregnant women). Many patients were critically ill on mechanical ventilation (41%) and renal replacement therapies (19%); 38% had received oseltamivir. The most frequently reported serious AEs by MedDRA preferred term were death (15%), H1N1 influenza (8%), respiratory failure (8%), acute renal failure (7%), and acute respiratory distress syndrome (7%). Six medication errors were reported. Most deaths occurred among patients who were obese, immunosuppressed, aged >65 years, or received oseltamivir. Rash was the only treatment-emergent AE attributable to peramivir. Influenza severity, comorbidities, and concomitant medications confounded additional peramivir AE assessments. Missing clinical and laboratory data precluded evaluation of some reports.
  
  
  CONCLUSIONS
  Many peramivir recipients under the EUA were critically ill and at risk for influenza-related complications. The safety data were insufficient to assess whether peramivir affected outcome or caused adverse reactions other than rash. Clinical trials in hospitalized patients with serious influenza infections should provide additional information.
authors.affiliation: Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland 20993, USA. alfred.sorbello@fda.hhs.gov
authors.forename: Alfred
authors.initials: A
authors.lastname: Sorbello
authors.forename: S Christopher
authors.initials: SC
authors.lastname: Jones
authors.forename: Wendy
authors.initials: W
authors.lastname: Carter
authors.forename: Kimberly
authors.initials: K
authors.lastname: Struble
authors.forename: Robert
authors.initials: R
authors.lastname: Boucher
authors.forename: Melissa
authors.initials: M
authors.lastname: Truffa
authors.forename: Debra
authors.initials: D
authors.lastname: Birnkrant
authors.forename: Neha
authors.initials: N
authors.lastname: Gada
authors.forename: Sara
authors.initials: S
authors.lastname: Camilli
authors.forename: Irene
authors.initials: I
authors.lastname: Chan
authors.forename: Scott
authors.initials: S
authors.lastname: Dallas
authors.forename: Twanda
authors.initials: T
authors.lastname: Scales
authors.forename: Robert
authors.initials: R
authors.lastname: Kosko
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thompson
authors.forename: Jesse
authors.initials: J
authors.lastname: Goodman
authors.forename: Henry
authors.initials: H
authors.lastname: Francis
authors.forename: Gerald
authors.initials: G
authors.lastname: Dal Pan
mesh_terms: D000146:Acids, Carbocyclic; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003517:Cyclopentanes / Q000008:administration & dosage / Q000009:adverse effects*; D004363:Drug Utilization; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000009:adverse effects*; D006760:Hospitalization; D006801:Humans; D007223:Infant; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D012307:Risk Factors; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D006146:Guanidines; C414210:peramivir