title: Comparative Risk of Anaphylactic Reactions Associated With Intravenous Iron Products.
abstract: OBJECTIVE
  All intravenous (IV) iron products are associated with anaphylaxis, but the comparative safety of each product has not been well established.
  
  
  OBJECTIVE
  To compare the risk of anaphylaxis among marketed IV iron products.
  
  
  METHODS
  Retrospective new user cohort study of IV iron recipients (n = 688,183) enrolled in the US fee-for-service Medicare program from January 2003 to December 2013. Analyses involving ferumoxytol were limited to the period January 2010 to December 2013.
  
  
  METHODS
  Administrations of IV iron dextran, gluconate, sucrose, or ferumoxytol as reported in outpatient Medicare claims data.
  
  
  METHODS
  Anaphylaxis was identified using a prespecified and validated algorithm defined with standard diagnosis and procedure codes and applied to both inpatient and outpatient Medicare claims. The absolute and relative risks of anaphylaxis were estimated, adjusting for imbalances among treatment groups.
  
  
  RESULTS
  A total of 274 anaphylaxis cases were identified at first exposure, with an additional 170 incident anaphylaxis cases identified during subsequent IV iron administrations. The risk for anaphylaxis at first exposure was 68 per 100,000 persons for iron dextran (95% CI, 57.8-78.7 per 100,000) and 24 per 100,000 persons for all nondextran IV iron products combined (iron sucrose, gluconate, and ferumoxytol) (95% CI, 20.0-29.5 per 100,000) , with an adjusted odds ratio (OR) of 2.6 (95% CI, 2.0-3.3; P < .001). At first exposure, when compared with iron sucrose, the adjusted OR of anaphylaxis for iron dextran was 3.6 (95% CI, 2.4-5.4); for iron gluconate, 2.0 (95% CI 1.2, 3.5); and for ferumoxytol, 2.2 (95% CI, 1.1-4.3). The estimated cumulative anaphylaxis risk following total iron repletion of 1000 mg administered within a 12-week period was highest with iron dextran (82 per 100,000 persons, 95% CI, 70.5- 93.1) and lowest with iron sucrose (21 per 100,000 persons, 95% CI, 15.3- 26.4).
  
  
  CONCLUSIONS
  Among patients in the US Medicare nondialysis population with first exposure to IV iron, the risk of anaphylaxis was highest for iron dextran and lowest for iron sucrose.
authors.affiliation: Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Cunlin
authors.initials: C
authors.lastname: Wang
authors.affiliation: Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: David J
authors.initials: DJ
authors.lastname: Graham
authors.affiliation: Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland3Dr Kane is now retired.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kane
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Diqiong
authors.initials: D
authors.lastname: Xie
authors.affiliation: Acumen LLC, Burlingame, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Wernecke
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Levenson
authors.affiliation: Acumen LLC, Burlingame, California.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: MaCurdy
authors.affiliation: Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Monica
authors.initials: M
authors.lastname: Houstoun
authors.affiliation: Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ryan
authors.affiliation: Acumen LLC, Burlingame, California.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wong
authors.affiliation: Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland6Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Katrina
authors.initials: K
authors.lastname: Mott
authors.affiliation: Acumen LLC, Burlingame, California.
authors.forename: Ting-Chang
authors.initials: TC
authors.lastname: Sheu
authors.affiliation: Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland7Genentech Inc, San Francisco, California.
authors.forename: Susan
authors.initials: S
authors.lastname: Limb
authors.affiliation: Centers for Medicare & Medicaid Services, Washington, DC.
authors.forename: Chris
authors.initials: C
authors.lastname: Worrall
authors.affiliation: Centers for Medicare & Medicaid Services, Washington, DC.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kelman
authors.affiliation: Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Marsha E
authors.initials: ME
authors.lastname: Reichman
mesh_terms: D000368:Aged; D000707:Anaphylaxis / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077605:Ferric Oxide, Saccharated; D052203:Ferrosoferric Oxide / Q000008:administration & dosage / Q000009:adverse effects*; D005937:Glucaric Acid / Q000008:administration & dosage / Q000009:adverse effects*; D005942:Gluconates / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D007275:Injections, Intravenous; D007505:Iron-Dextran Complex / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D016344:Medicare Part A / Q000706:statistics & numerical data; D012189:Retrospective Studies; D012306:Risk; D014481:United States / Q000453:epidemiology
chemical_list: D005290:Ferric Compounds; D005942:Gluconates; D007505:Iron-Dextran Complex; D000077605:Ferric Oxide, Saccharated; D005937:Glucaric Acid; D052203:Ferrosoferric Oxide