{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T21:38:46Z","timestamp":1758404326841,"version":"3.40.5"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,1,20]],"date-time":"2021-01-20T00:00:00Z","timestamp":1611100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013120","name":"European Medicines Agency","doi-asserted-by":"publisher","award":["EMA\/2014\/50\/RE"],"award-info":[{"award-number":["EMA\/2014\/50\/RE"]}],"id":[{"id":"10.13039\/501100013120","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Hydroxyzine is indicated for the management of anxiety, skin and sleep disorders. In 2015, the European Medicines Agency (EMA) concluded that hydroxyzine was pro\u2010arrhythmogenic and changes to the product information were implemented in Europe. This study aimed to evaluate their impact in Denmark, Scotland, England and the Netherlands.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hydroxyzine initiation in quarter one 2010 in Denmark, Scotland, England and the Netherlands per 100\u2009000 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\u2009000 in England (\u221212.05, 95%CI \u221218.47 to \u22125.63) and Scotland (\u221219.01, 95%CI \u221226.99 to \u221211.02); change to a negative trend in hydroxyzine initiation per 100\u2009000\/quarter in England (\u22121.72, 95%CI \u22122.69 to \u22120.75) and Scotland (\u22122.38, 95%CI \u22123.32 to \u22121.44). Regulatory action was associated with a significant: immediate rise in hydroxyzine discontinuation per 100\u2009000 in England (3850, 95%CI 440\u20107240). 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.5191","type":"journal-article","created":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T07:15:58Z","timestamp":1609571758000},"page":"482-491","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Impact of <scp>EMA<\/scp> 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"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0063-8069","authenticated-orcid":false,"given":"Daniel R.","family":"Morales","sequence":"first","affiliation":[{"name":"MEMO Research, University of Dundee  Dundee UK"},{"name":"Department of Clinical Pharmacology and Pharmacy University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Macfarlane","sequence":"additional","affiliation":[{"name":"MEMO Research, University of Dundee  Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5189-6669","authenticated-orcid":false,"given":"Thomas M.","family":"MacDonald","sequence":"additional","affiliation":[{"name":"MEMO Research, University of Dundee  Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8097-8708","authenticated-orcid":false,"given":"Jesper","family":"Hallas","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacy University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin Thomsen","family":"Ernst","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacy University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron M. C.","family":"Herings","sequence":"additional","affiliation":[{"name":"PHARMO Institute for Drug Outcomes Research  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Smits","sequence":"additional","affiliation":[{"name":"PHARMO Institute for Drug Outcomes Research  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jetty A.","family":"Overbeek","sequence":"additional","affiliation":[{"name":"PHARMO Institute for Drug Outcomes Research  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyn","family":"Mitchell","sequence":"additional","affiliation":[{"name":"MEMO Research, University of Dundee  Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Morant","sequence":"additional","affiliation":[{"name":"MEMO Research, University of Dundee  Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isla","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"MEMO Research, University of Dundee  Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander S. F.","family":"Doney","sequence":"additional","affiliation":[{"name":"MEMO Research, University of Dundee  Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Robertson","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics University of Strathclyde  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Bennie","sequence":"additional","affiliation":[{"name":"Strathclyde Onstitute of Pharmacy and Biomedical Sciences University of Strathclyde  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Pharmacy University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lizzie","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Electronic Data Research and Innovation Service NHS National Services Scotland  Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carole","family":"Morris","sequence":"additional","affiliation":[{"name":"Electronic Data Research and Innovation Service NHS National Services Scotland  Edinburgh UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert W. F.","family":"Flynn","sequence":"additional","affiliation":[{"name":"MEMO Research, University of Dundee  Dundee UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,1,20]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"European Medicines Agency. PRAC recommends new measures to minimise known heart risks of hydroxyzine\u2010containing medicines. Available at:https:\/\/www.ema.europa.eu\/en\/news\/prac\u2010recommends\u2010new\u2010measures\u2010minimise\u2010known\u2010heart\u2010risks\u2010hydroxyzine\u2010containing\u2010medicinesAccessed 19\/09\/2019."},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MLR.0b013e318245a160"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13469"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv098"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyw060"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-014-9930-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S91125"},{"issue":"3","key":"e_1_2_9_9_1","first-page":"798","article-title":"Data resource profile: the Danish National Prescription Registry","volume":"46","author":"Pottegard A","year":"2017","journal-title":"Int J Epidemiol"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehl391"},{"key":"e_1_2_9_11_1","unstructured":"EU PAS Register.Impact of EU label changes for hydroxyzine products: post\u2010referral prescribing trends.http:\/\/www.encepp.eu\/encepp\/viewResource.htm?id=31082."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2710.2002.00430.x"},{"key":"e_1_2_9_13_1","unstructured":"Information Services Division Scotland. Prescription cost analysis;2016.https:\/\/www.isdscotland.org\/Health\u2010Topics\/Prescribing\u2010and\u2010Medicines\/Community\u2010Dispensing\/Prescription\u2010Cost\u2010Analysis\/. Accessed 20\/01\/2020."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2165\/11539040-000000000-00000"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14104"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0068976"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-017-0538-x"},{"key":"e_1_2_9_18_1","unstructured":"Medicines Evaluation Board. Lower dosage for drugs containing hydroxyzine. 2015. Available at:https:\/\/www.apothekersnieuws.nl\/lagere-dosering-voor-geneesmiddelen-met-hydroxyzine. Accessed 22\/10\/2020."},{"key":"e_1_2_9_19_1","unstructured":"Alliance. New restrictions for hydroxyzine\u2010containing medicines to further minimize the known risks of QT prolongation. 2015. 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