Hydroxyzine Initiation Following Drug Safety Advisories on Cardiac Arrhythmias in the UK and Canada: A Longitudinal Cohort Study

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  • Richard L. Morrow
  • Barbara Mintzes
  • Patrick C. Souverein
  • Hallgreen, Christine Erikstrup
  • Bilal Ahmed
  • Elizabeth E. Roughead
  • Marie L. De Bruin
  • Sarah Brøgger Kristiansen
  • Joel Lexchin
  • Anna Kemp-Casey
  • Ingrid Sketris
  • Dee Mangin
  • Sallie Anne Pearson
  • Lorri Puil
  • Ruth Lopert
  • Lisa Bero
  • Danijela Gnjidic
  • Ameet Sarpatwari
  • Colin R. Dormuth

Introduction: Regulatory advisories on hydroxyzine and risk of QT prolongation and Torsade de pointes (TdP) were issued in the UK in April 2015 and Canada in June 2016. We hypothesized patients with risk factors for QT prolongation and TdP, compared with those without risk factors, would be less likely to initiate hydroxyzine in the UK and in British Columbia (BC), Canada, following advisories. Methods: We conducted a longitudinal study with repeated measures, and evaluated hydroxyzine initiation in a UK cohort and a concurrent BC control cohort (April 2013–March 2016) as well as in a BC advisory cohort (June 2014–May 2017). Results: This study included 247,665 patients in the UK cohort, 297,147 patients in the BC control cohort, and 303,653 patients in the BC advisory cohort. Over a 12-month post-advisory period, hydroxyzine initiation decreased by 21% in the UK (rate ratio 0.79, 95% confidence interval 0.66–0.96) relative to the expected level of initiation based on the pre-advisory trend. Hydroxyzine initiation did not change in the BC control cohort or following the Canadian advisory in the BC advisory cohort. The decrease in hydroxyzine initiation in the UK in the 12 months after the advisories was not significantly different for patients with risk factors compared with those without risk factors. Conclusion: Hydroxyzine initiation decreased in the UK, but not in BC, in the 12 months following safety advisories. The decrease in hydroxyzine initiation in the UK was not significantly different for patients with versus without risk factors for QT prolongation and TdP.

Original languageEnglish
JournalDrug Safety
Pages (from-to)623–638
Publication statusPublished - 2022

Bibliographical note

Funding Information:
The authors declare that grants from the CIHR and Australia’s NHMRC supported this work. Joel Lexchin declares payments from the CIHR, the Toronto Public Library and from lawyers acting on behalf of clients allegedly affected by adverse drug reactions. Marie L. De Bruin and Christine E. Hallgreen declare PhD grants from Novo Nordisk, Lundbeck, Ferring Pharmaceuticals, and LEO Pharma to the Copenhagen Centre for Regulatory Science. Barbara Mintzes is acting as an expert witness for Health Canada on a legal case and anticipates future payment for doing so. Sallie-Anne Pearson declares the Centre for Big Data Research in Health received funding for postmarket surveillance research, unrelated to the current study. Lorri Puil has received a Michael Smith Foundation for Health Research Reach Grant. Ameet Sarpatwari declares grants or contracts from Arnold Ventures, and the US FDA paid, to his institution, consulting fees from West Health, and payment for expert testimony from the American Civil Liberties Union (ACLU). Ingrid Sketris has received a CIHR Canadian Network for Observational Drug Effect Studies grant and a Drug Evaluation Alliance of Nova Scotia grant, as well as payment for serving as a member of the Patented Medicine Prices Review Board. Richard L. Morrow, Patrick C. Souverein, Bilal Ahmed, Elizabeth E. Roughead, Sarah Brøgger Kristiansen, Anna Kemp-Casey, Dee Mangin, Ruth Lopert, Lisa Bero, Danijela Gnjidic, and Colin R. Dormuth report no conflicts of interest and all authors declare no other relationships or activities that could appear to have influenced the submitted work.

Funding Information:
This work was funded by grants from the Canadian Institutes of Health Research (CIHR; PJT–153275) and the Australian Government National Health and Medical Research Council (NHMRC; 1122332). Ameet Sarpatwari’s work is also funded by Arnold Ventures.

Publisher Copyright:
© 2022, The Author(s).

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