title: Off-Label Use of Agents for Management of Serious or Life-threatening Angiotensin Converting Enzyme Inhibitor-Induced Angioedema.
abstract: OBJECTIVE
  To evaluate the place in therapy of fresh frozen plasma (FFP), C1 esterase concentrate (C1-INH), ecallantide, and icatibant in the management of angiotensin-converting enzyme inhibitor-induced angioedema (ACEI-IA).
  
  
  METHODS
  A literature search was performed using PubMed (1946 through August 2015) and Embase (<1966 through August 2015). References from identified articles were reviewed.
  
  
  METHODS
  Consensus papers, practice guidelines, case reports/series, clinical trials, and meeting abstracts published in English and involving humans were included.
  
  
  RESULTS
  No medications are currently Food and Drug Administration-approved for managing ACEI-IA. Emerging evidence suggests that FFP and medications approved for management of acute attacks of hereditary angioedema, another bradykinin-mediated event, may be effective for use in ACEI-IA. Positive efficacy results were reported with FFP and C1-INH while mixed results have been seen with ecallantide. Off-label icatibant has the most evidence supporting its use in ACEI-IA with rapid symptom resolution (10 minutes to 6 hours) and avoidance of intubation and tracheotomy in several cases. These agents were well-tolerated in ACEI-IA.
  
  
  CONCLUSIONS
  ACEI-IA is typically a self-limiting event. First-line therapies include ACEI discontinuation, observation, and supportive medications (eg, corticosteroids, antihistamines, and epinephrine). Symptom progression can be life-threatening and may require interventions such as tracheotomy and intubation. Off-label use of FFP and medications approved for hereditary angioedema have resulted in rapid resolution of symptoms and avoidance of intubation. Among these agents, icatibant has the most supporting evidence and has been incorporated into practice guidelines and algorithms as a second-line agent for serious life-threatening ACE-IA.
authors.affiliation: University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA UPMC Pharmacy Service Line, Pittsburgh, PA, USA culleycm@upmc.edu.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Culley
authors.affiliation: UPMC Presbyterian, Pittsburgh, PA, USA.
authors.forename: Julie N
authors.initials: JN
authors.lastname: DiBridge
authors.affiliation: UPMC Pharmacy Service Line, Pittsburgh, PA, USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Wilson
mesh_terms: D000799:Angioedema / Q000139:chemically induced* / Q000628:therapy; D054179:Angioedemas, Hereditary / Q000188:drug therapy; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects*; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D003173:Complement C1s / Q000627:therapeutic use; D006801:Humans; D056687:Off-Label Use; D010455:Peptides / Q000627:therapeutic use; D010949:Plasma; D014481:United States
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D010455:Peptides; C511194:ecallantide; C065679:icatibant; D003173:Complement C1s; D001920:Bradykinin
keywords: C1 esterase inhibitor; angioedema; angiotensin-converting enzyme; ecallantide; fresh frozen plasma; icatibant