Impact of EMA regulatory label changes on hydroxyzine initiation, discontinuation and switching to other medicines in Denmark, Scotland, England and the Netherlands: An interrupted time series regression analysis

Daniel R. Morales*, Tatiana Macfarlane, Thomas M. MacDonald, Jesper Hallas, Martin Thomsen Ernst, Ron M.C. Herings, Elisabeth Smits, Jetty A. Overbeek, Lyn Mitchell, Steven Morant, Isla Mackenzie, Alexander S.F. Doney, Chris Robertson, Marion Bennie, Li Wei, Lizzie Nicholson, Carole Morris, Robert W.F. Flynn

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
TidsskriftPharmacoepidemiology and Drug Safety
Vol/bind30
Udgave nummer4
Sider (fra-til)482-491
ISSN1053-8569
DOI
StatusUdgivet - apr. 2021

Bibliografisk note

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.

Publisher Copyright:
© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

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