title: Six years without pholcodine; Norwegians are significantly less IgE-sensitized and clinically more tolerant to neuromuscular blocking agents.
abstract: BACKGROUND
  As a strong inducer of IgE antibodies to substituted ammonium ion epitopes (QAI), pholcodine (PHO) is a postulated cause of allergic anaphylaxis to neuromuscular blocking agents (NMBAs). Three years after withdrawal of PHO in Norway, a significant reduction in IgE sensitization and anaphylaxis reporting was seen.
  
  
  OBJECTIVE
  Six-year follow-up study on the effects of PHO withdrawal on IgE sensitization and anaphylaxis reporting.
  
  
  METHODS
  From 650 acute consecutive reports (2005-2013) to the Norwegian Network for Anaphylaxis under Anaesthesia (NARA), total number of reports on suspected anaphylactic reactions, number of reactions where NMBAs were administered, number of reactions where serum IgE antibodies (≥0.35 kUA/l) to suxamethonium (SUX) and PHO were present at time of reaction and anaphylaxis severity grades were retrieved. In addition, NMBA sales and prevalence of IgE sensitization to PHO and SUX among 'allergics' were monitored.
  
  
  RESULTS
  From baseline period P0 (PHO on the market) through the first (P1) and second (P2), three-year periods after withdrawal, significant falls in total reports (P < 0.001) and reports with IgE antibodies to PHO (P = 0.008) and SUX (P = 0.001) at time of reaction were found. Total NMBA sales in P2 were 83% of P0, and SUX and rocuronium (ROC) together made up 86% of sales throughout the study. Five NMBA-related anaphylactic deaths occurred during P0 and P1 and, however, none during P2. Prevalence of IgE sensitization to SUX in 'allergics' fell to 0% at 4 and 5 years after withdrawal.
  
  
  CONCLUSIONS
  Six years after PHO withdrawal, the Norwegian population has become significantly less IgE-sensitized and clinically more tolerant to NMBAs.
authors.affiliation: Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.
authors.forename: G H
authors.initials: GH
authors.lastname: de Pater
authors.affiliation: Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway.|Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Florvaag
authors.affiliation: Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institute, Stockholm, Sweden.|Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: S G O
authors.initials: SG
authors.lastname: Johansson
authors.affiliation: Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Å
authors.initials: Å
authors.lastname: Irgens
authors.affiliation: Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.
authors.forename: M N H
authors.initials: MN
authors.lastname: Petersen
authors.affiliation: Department of Anaesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.|Department of Clinical Medicine, Section of Anaesthesiology and Intensive Care, University of Bergen, Bergen, Norway.
authors.forename: A B
authors.initials: AB
authors.lastname: Guttormsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000453:epidemiology* / Q000209:etiology*; D002648:Child; D003061:Codeine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry; D004342:Drug Hypersensitivity / Q000453:epidemiology* / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects* / Q000737:chemistry; D009466:Neuromuscular Blocking Agents / Q000009:adverse effects*; D009664:Norway / Q000453:epidemiology; D011159:Population Surveillance; D015995:Prevalence; D056737:Safety-Based Drug Withdrawals; D055815:Young Adult
chemical_list: D009025:Morpholines; D009466:Neuromuscular Blocking Agents; D007073:Immunoglobulin E; C008872:pholcodine; D003061:Codeine
keywords: IgE antibodies; anaesthesia; anaphylaxis; pholcodine