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 - This article is protected by copyright. All rights reserved.
PY - 2021/1/1
Y1 - 2021/1/1
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 2009-2018. 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 to 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 2009-2018. 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 to 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
U2 - 10.1002/pds.5191
DO - 10.1002/pds.5191
M3 - Article
C2 - 33386650
JO - Pharmacoepidemiology and Drug Safety
JF - Pharmacoepidemiology and Drug Safety
SN - 1053-8569
ER -