TY - JOUR
T1 - Impact of EMA regulatory label changes on hydroxyzine initiation, discontinuation and switching to other medicines in Denmark, Scotland, England and the Netherlands
T2 - an interrupted time series regression analysis
AU - Morales, Daniel R.
AU - Macfarlane, Tatiana
AU - MacDonald, Thomas M.
AU - Hallas, Jesper
AU - Ernst, Martin Thomsen
AU - Herings, Ron M. C.
AU - Smits, Elisabeth
AU - Overbeek, Jetty A.
AU - Mitchell, Lyn
AU - Morant, Steven
AU - Mackenzie, Isla
AU - Doney, Alexander
AU - Robertson, Chris
AU - Bennie, Marion
AU - Wei, Li
AU - Nicholson, Lizzie
AU - Morris, Carole
AU - Flynn, Robert W. F.
N1 - Funding Information:
The authors acknowledge the Electronic Data Research and Innovation Service (eDRIS) of ISD Scotland for providing the Scottish data and for the general practices that contributed data to CPRD for public health purposes. The study was funded by the European Medicines Agency (Procurement procedure EMA/2014/50/RE). The EMA approved the final study protocol and had no influence on the results or decision to publish.
Funding Information:
Elisabeth Smitsm Jetty A. Overbeek and Ron M. C. Herings are employees of the PHARMO Institute for Drug Outcomes Research. This independent research institute performs financially supported studies for government and related healthcare authorities and several pharmaceutical companies. TMM's university holds research grants from Novartis, Ipsen, Teijin & Menarini. He is or has been the Principal Investigator on trials paid for by Novartis, Ipsen, Teijin, RTI, GlaxoSmithKline, SHIRE and Menarini. In the last 3 years he has been paid consulting fees by Novartis and Merck. None of these studies relate to hydroxyzine.
Funding Information:
The authors acknowledge the Electronic Data Research and Innovation Service (eDRIS) of ISD Scotland for providing the Scottish data and for the general practices that contributed data to CPRD for public health purposes. The study was funded by the European Medicines Agency (Procurement procedure EMA/2014/50/RE). The EMA approved the final study protocol and had no influence on the results or decision to publish.
Publisher Copyright:
© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - Background: Hydroxyzine is indicated for the management of anxiety, skin and sleep disorders. In 2015, the European Medicines Agency (EMA) concluded that hydroxyzine was pro-arrhythmogenic and changes to the product information were implemented in Europe. This study aimed to evaluate their impact in Denmark, Scotland, England and the Netherlands. Method: Quarterly time series analyses measuring hydroxyzine initiation, discontinuation, and switching to other antihistamines, benzodiazepines and antidepressants in Denmark, England, Scotland and the Netherlands from 2009 to 2018. Data were analysed using interrupted time series regression. Results: Hydroxyzine initiation in quarter one 2010 in Denmark, Scotland, England and the Netherlands per 100 000 was: 23.5, 91.5, 35.9 and 34.4 respectively. Regulatory action was associated with a significant: immediate fall in hydroxyzine initiation per 100 000 in England (−12.05, 95%CI −18.47 to −5.63) and Scotland (−19.01, 95%CI −26.99 to −11.02); change to a negative trend in hydroxyzine initiation per 100 000/quarter in England (−1.72, 95%CI −2.69 to −0.75) and Scotland (−2.38, 95%CI −3.32 to −1.44). Regulatory action was associated with a significant: immediate rise in hydroxyzine discontinuation per 100 000 in England (3850, 95%CI 440-7240). No consistent changes were observed in the Netherlands or Denmark. Regulatory action was associated with no switching to other antihistamines, benzodiazepines or antidepressants following hydroxyzine discontinuation in any country. Conclusion: The 2015 EMA regulatory action was associated with heterogeneous impact with reductions in hydroxyzine initiation varying by country. There was limited impact on discontinuation with no strong evidence suggesting unintended consequences of major switching to other antihistamines, benzodiazepines or antidepressants.
AB - Background: Hydroxyzine is indicated for the management of anxiety, skin and sleep disorders. In 2015, the European Medicines Agency (EMA) concluded that hydroxyzine was pro-arrhythmogenic and changes to the product information were implemented in Europe. This study aimed to evaluate their impact in Denmark, Scotland, England and the Netherlands. Method: Quarterly time series analyses measuring hydroxyzine initiation, discontinuation, and switching to other antihistamines, benzodiazepines and antidepressants in Denmark, England, Scotland and the Netherlands from 2009 to 2018. Data were analysed using interrupted time series regression. Results: Hydroxyzine initiation in quarter one 2010 in Denmark, Scotland, England and the Netherlands per 100 000 was: 23.5, 91.5, 35.9 and 34.4 respectively. Regulatory action was associated with a significant: immediate fall in hydroxyzine initiation per 100 000 in England (−12.05, 95%CI −18.47 to −5.63) and Scotland (−19.01, 95%CI −26.99 to −11.02); change to a negative trend in hydroxyzine initiation per 100 000/quarter in England (−1.72, 95%CI −2.69 to −0.75) and Scotland (−2.38, 95%CI −3.32 to −1.44). Regulatory action was associated with a significant: immediate rise in hydroxyzine discontinuation per 100 000 in England (3850, 95%CI 440-7240). No consistent changes were observed in the Netherlands or Denmark. Regulatory action was associated with no switching to other antihistamines, benzodiazepines or antidepressants following hydroxyzine discontinuation in any country. Conclusion: The 2015 EMA regulatory action was associated with heterogeneous impact with reductions in hydroxyzine initiation varying by country. There was limited impact on discontinuation with no strong evidence suggesting unintended consequences of major switching to other antihistamines, benzodiazepines or antidepressants.
KW - hydroxyzine
KW - pharmacoepidemiology
KW - pharmacovigilance
KW - prescribing
KW - regulation
KW - time-series
UR - http://www.scopus.com/inward/record.url?scp=85099667259&partnerID=8YFLogxK
U2 - 10.1002/pds.5191
DO - 10.1002/pds.5191
M3 - Article
C2 - 33386650
VL - 30
SP - 482
EP - 491
JO - Pharmacoepidemiology and Drug Safety
JF - Pharmacoepidemiology and Drug Safety
SN - 1053-8569
IS - 4
ER -