title: Epinephrine Use in Clinical Trials of Sublingual Immunotherapy Tablets.
abstract: Allergy immunotherapy can result in systemic allergic reactions and even life-threatening anaphylaxis requiring epinephrine administration.
  
  
  
  The objective of this study was to describe epinephrine use in the clinical trial development programs of 3 rapidly dissolving sublingual immunotherapy tablets (SLIT-tablets; Merck & Co., Inc., Kenilworth, NJ/ALK, Hørsholm, Denmark/Torii Pharmaceutical Co., Ltd., Tokyo, Japan).
  
  
  
  Data on epinephrine use were collected from 13 timothy grass SLIT-tablet trials (MK-7243; ≤2800 bioequivalent allergen units/75,000 SQ-T dose, n = 2497; placebo, n = 2139), 5 short ragweed SLIT-tablet trials (MK-3641; ≤12 Amb a 1-U, n = 1725; placebo, n = 770), and 11 house dust mite (HDM) SLIT-tablet trials (MK-8237; ≤12 SQ-HDM; n = 3930; placebo, n = 2246).
  
  
  
  In grass SLIT-tablet trials, epinephrine was used 13 times (grass SLIT-tablet, n = 10; placebo, n = 3). Eight administrations were for grass SLIT-tablet-related adverse events (AEs): 4 for systemic allergic reactions and 4 for local mouth and/or throat swelling. In ragweed SLIT-tablet trials, epinephrine was used 9 times in 8 subjects (ragweed SLIT-tablet, n = 7; placebo, n = 1 [2 administrations for protracted anaphylaxis]). Four administrations were for ragweed SLIT-tablet-related AEs: 1 for systemic allergic reaction and 3 for local mouth and/or pharynx/throat swelling. In HDM SLIT-tablet trials, epinephrine was administered 13 times (HDM SLIT-tablet, n = 8; placebo, n = 5). Four administrations were for HDM SLIT-tablet-related AEs: 1 for systemic allergic reaction and 3 for local events. Of the 16 epinephrine administrations for events related to SLIT-tablet treatment, 11 occurred within the first week of treatment (7 administrations on day 1) and 5 were subject self-administered.
  
  
  
  Epinephrine administrations in response to SLIT-tablet-related reactions in clinical trials are uncommon, typically occur within the first week of treatment, and are rarely self-administered. All SLIT-tablet-related events treated with epinephrine were nonserious.
authors.affiliation: Research and Development, Merck & Co., Inc., Kenilworth, NJ. Electronic address: hendrik.nolte@merck.com.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Nolte
authors.affiliation: Division of Allergy & Immunology, University of South Florida Morsani College of Medicine, Tampa, Fla.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Casale
authors.affiliation: Division of Allergy & Immunology, University of South Florida Morsani College of Medicine, Tampa, Fla.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Lockey
authors.affiliation: ALK, Hørsholm, Denmark.
authors.forename: Bodil Svanholm
authors.initials: BS
authors.lastname: Fogh
authors.affiliation: Research and Development, Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Amarjot
authors.initials: A
authors.lastname: Kaur
authors.affiliation: Research and Development, Merck & Co., Inc., Kenilworth, NJ.
authors.forename: Susan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Medicine, National Jewish Health, Denver, Colo.
authors.forename: Harold S
authors.initials: HS
authors.lastname: Nelson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D031164:Ambrosia; D000707:Anaphylaxis / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000627:therapeutic use*; D052179:Antigens, Plant / Q000627:therapeutic use*; D001249:Asthma / Q000150:complications / Q000276:immunology / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D004837:Epinephrine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D031784:Phleum; D039981:Pyroglyphidae; D065631:Rhinitis, Allergic / Q000150:complications / Q000276:immunology / Q000628:therapy*; D063729:Sublingual Immunotherapy / Q000009:adverse effects / Q000379:methods*; D013607:Tablets; D055815:Young Adult
chemical_list: D039741:Antigens, Dermatophagoides; D052179:Antigens, Plant; D013607:Tablets; D004837:Epinephrine
keywords: Adrenaline; Allergen immunotherapy; Anaphylaxis; Epinephrine; Safety; Sublingual immunotherapy; Systemic allergic reaction