PMID- 27838323
OWN - NLM
STAT- MEDLINE
DCOM- 20171102
LR  - 20181012
IS  - 2213-2201 (Electronic)
VI  - 5
IP  - 1
DP  - 2017 Jan-Feb
TI  - Epinephrine Use in Clinical Trials of Sublingual Immunotherapy Tablets.
PG  - 84-89.e3
LID - S2213-2198(16)30402-0 [pii]
LID - 10.1016/j.jaip.2016.08.017 [doi]
AB  - BACKGROUND: Allergy immunotherapy can result in systemic allergic reactions and 
      even life-threatening anaphylaxis requiring epinephrine administration. 
      OBJECTIVE: 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, 
      Horsholm, Denmark/Torii Pharmaceutical Co., Ltd., Tokyo, Japan). METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.
CI  - Copyright (c) 2016 American Academy of Allergy, Asthma & Immunology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Nolte, Hendrik
AU  - Nolte H
AD  - Research and Development, Merck & Co., Inc., Kenilworth, NJ. Electronic address: 
      hendrik.nolte@merck.com.
FAU - Casale, Thomas B
AU  - Casale TB
AD  - Division of Allergy & Immunology, University of South Florida Morsani College of 
      Medicine, Tampa, Fla.
FAU - Lockey, Richard F
AU  - Lockey RF
AD  - Division of Allergy & Immunology, University of South Florida Morsani College of 
      Medicine, Tampa, Fla.
FAU - Fogh, Bodil Svanholm
AU  - Fogh BS
AD  - ALK, Horsholm, Denmark.
FAU - Kaur, Amarjot
AU  - Kaur A
AD  - Research and Development, Merck & Co., Inc., Kenilworth, NJ.
FAU - Lu, Susan
AU  - Lu S
AD  - Research and Development, Merck & Co., Inc., Kenilworth, NJ.
FAU - Nelson, Harold S
AU  - Nelson HS
AD  - Department of Medicine, National Jewish Health, Denver, Colo.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20161109
PL  - United States
TA  - J Allergy Clin Immunol Pract
JT  - The journal of allergy and clinical immunology. In practice
JID - 101597220
RN  - 0 (Antigens, Dermatophagoides)
RN  - 0 (Antigens, Plant)
RN  - 0 (Tablets)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
CIN - J Allergy Clin Immunol Pract. 2017 Jan - Feb;5(1):90-91. PMID: 28065345
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Ambrosia
MH  - Anaphylaxis/etiology/*prevention & control
MH  - Animals
MH  - Antigens, Dermatophagoides/*therapeutic use
MH  - Antigens, Plant/*therapeutic use
MH  - Asthma/complications/immunology/*therapy
MH  - Child
MH  - Child, Preschool
MH  - Epinephrine/*administration & dosage
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Phleum
MH  - Pyroglyphidae
MH  - Rhinitis, Allergic/complications/immunology/*therapy
MH  - Sublingual Immunotherapy/adverse effects/*methods
MH  - Tablets
MH  - Young Adult
OTO - NOTNLM
OT  - Adrenaline
OT  - Allergen immunotherapy
OT  - Anaphylaxis
OT  - Epinephrine
OT  - Safety
OT  - Sublingual immunotherapy
OT  - Systemic allergic reaction
EDAT- 2016/11/14 06:00
MHDA- 2017/11/03 06:00
CRDT- 2016/11/14 06:00
PHST- 2016/03/24 00:00 [received]
PHST- 2016/08/09 00:00 [revised]
PHST- 2016/08/23 00:00 [accepted]
PHST- 2016/11/14 06:00 [pubmed]
PHST- 2017/11/03 06:00 [medline]
PHST- 2016/11/14 06:00 [entrez]
AID - S2213-2198(16)30402-0 [pii]
AID - 10.1016/j.jaip.2016.08.017 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol Pract. 2017 Jan-Feb;5(1):84-89.e3. doi: 
      10.1016/j.jaip.2016.08.017. Epub 2016 Nov 9.