Hydroxyzine initiation following drug safety advisories on cardiac arrhythmias in the UK and Canada: a longitudinal cohort study

Saturday, August 27, 2022

2:10 PM – 2:15 PM CEST

Location: C1M2

Publication Number: 181

Background: 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. Advisories highlighted that patients with risk factors for QT prolongation and TdP, such as underlying heart conditions and concomitant use of QT-prolonging drugs, were at higher risk of these adverse events.

Objectives: To determine whether patient risk factors for QT prolongation and TdP modified the effect of hydroxyzine advisories on hydroxyzine initiation in the UK and British Columbia (BC), Canada. We hypothesized patients with risk factors for QT prolongation and TdP, compared to 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. We evaluated hydroxyzine initiation among patients who had recently visited a physician for contact dermatitis and other eczema, rash, urticaria, allergy, pruritus, atopic dermatitis, or scabies. Study cohorts included a UK cohort and a concurrent BC control cohort (April 2013 – March 2016) and a BC advisory cohort (June 2014 – May 2017).

Results: The 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. Our analysis of hydroxyzine initiation in the UK in the 12 months after the advisories indicated a lack of statistically significant effect modification for underlying heart conditions (RR 0.86; 95% CI 0.70–1.07) and recent use of QT-prolonging drugs with known risk of TdP (RR 0.82; 95% CI 0.63–1.07), as well as for other risk factors for QT prolongation and TdP.

Conclusions: 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 did not differ for patients with risk factors for QT prolongation and TdP, compared to those without risk factors.

Presenting Author(s)

Richard L. Morrow, PhD

Senior Research Analyst
Therapeutics Initiative, Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia
Victoria, British Columbia, Canada

Slides

Co-Author(s)

Barbara Mintzes, PhD

University of Sydney
Petersham, New South Wales, Australia
Patrick Souverein

Utrecht University, Netherlands
CH

Christine E. Hallgreen

Copenhagen Centre for Regulatory Science, University of Copenhagen
Copenhagen, Denmark
BA

Bilal Ahmed

University of British Columbia, Canada
ER

Elizabeth Roughead

University of South Australia, Australia
MD

Marie Louise De Bruin

Professor
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584CG Utrecht, The Netherlands, Netherlands
SK

Sarah Kristiansen

Postdoctoral researcher, data manager
Pharmacovigilance Research Center, Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark
Vanløse, Hovedstaden, Denmark
JL

Joel Lexchin

York University, Canada
AK

Anna Kemp-Casey

University of South Australia, Australia
Ingrid Sketris, FISPE

Dalhousie University
College of Pharmacy, Dalhousie University
Halifax, Nova Scotia, Canada
DM

Dee Mangin, MBChB (Otago), DPH (Otago), FRNZCGP (NZ)

Professor
McMaster University
Hamilton, ON, Canada
SP

Sallie-Anne Pearson, PhD

Director, Centre of Research Excellence in Medicines Intelligence
Centre for Big Data Research in Health, Faculty of Medicine and Health, University of New South Wales, Sydney, Australia, New South Wales, Australia
LP

Lorri Puil

University of British Columbia, Canada
RL

Ruth Lopert

George Washington University, United States
LB

Lisa Bero

University of Colorado Anschutz Medical Campus, United States
Danijela Gnjidic

Associate Professor
University of Sydney
The University Of Sydney, New South Wales, Australia
Ameet Sarpatwari, PhD, JD

Assistant Professor of Medicine
Brigham and Women’s Hospital and Harvard Medical School
Boston, MA, United States
CD

Colin Dormuth

University of British Columbia
Victoria, British Columbia, Canada