Off-label postpartum use of domperidone in Canada: a multidatabase cohort study

Carolina Moriello; J Michael Paterson; Pauline Reynier; Matthew Dahl; Wusiman Aibibula; Anat Fisher; John-Michael Gamble; I Fan Kuo; Paul E Ronksley; Brandace Winquist; Kristian B Filion; Canadian Network for Observational Drug Effect Studies (CNODES) Investigators

doi:10.9778/cmajo.20200084

Off-label postpartum use of domperidone in Canada: a multidatabase cohort study

CMAJ Open. 2021 May 14;9(2):E500-E509. doi: 10.9778/cmajo.20200084. Print 2021 Apr-Jun.

Affiliations

¹ Centre for Clinical Epidemiology (Moriello, Reynier, Aibibula, Filion), Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Que; ICES (Paterson); Institute of Health Policy, Management and Evaluation (Paterson), University of Toronto, Toronto, Ont.; Manitoba Centre for Health Policy, Department of Community Health Sciences (Dahl, Kuo), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Department of Anesthesiology, Pharmacology and Therapeutics (Fisher), University of British Columbia, Vancouver BC; School of Pharmacy (Gamble), University of Waterloo, Kitchener, Ont.; Department of Community Health Sciences (Ronksley), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Saskatchewan Health Quality Council (Winquist); Department of Community Health and Epidemiology (Winquist), College of Medicine, University of Saskatchewan, Saskatoon Sask.; Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health (Filion), McGill University, Montréal, Que.
² Centre for Clinical Epidemiology (Moriello, Reynier, Aibibula, Filion), Lady Davis Institute, Jewish General Hospital, McGill University, Montréal, Que; ICES (Paterson); Institute of Health Policy, Management and Evaluation (Paterson), University of Toronto, Toronto, Ont.; Manitoba Centre for Health Policy, Department of Community Health Sciences (Dahl, Kuo), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Department of Anesthesiology, Pharmacology and Therapeutics (Fisher), University of British Columbia, Vancouver BC; School of Pharmacy (Gamble), University of Waterloo, Kitchener, Ont.; Department of Community Health Sciences (Ronksley), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Saskatchewan Health Quality Council (Winquist); Department of Community Health and Epidemiology (Winquist), College of Medicine, University of Saskatchewan, Saskatoon Sask.; Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health (Filion), McGill University, Montréal, Que. kristian.filion@mcgill.ca.

Abstract

Background: Trends in off-label postpartum use of domperidone and the impact of safety advisories on its use remain unknown. Our objectives were to describe postpartum use of domperidone in Canada, to evaluate the impact of Health Canada advisories on prescribing patterns, and to describe the association between domperidone use and a composite end point of sudden cardiac death or ventricular tachycardia (VT) among postpartum patients.

Methods: We conducted a multidatabase cohort study involving pregnant patients with live births between 2004 and 2017 using administrative health databases from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario). We excluded patients with less than 1 year of prepregnancy database history and with approved indications for domperidone. We assessed domperidone use in the 6 months postpartum and the impact of the 2012 and 2015 Health Canada advisories on prescribing via interrupted time series analysis. We estimated crude rates of VT and sudden cardiac death.

Results: We included 1 190 987 live births. Mean maternal age was 28.6 (standard error 0.6) years. Domperidone use increased over time, from 7% in 2003-2005 to 12% in 2009-2011, when it plateaued. The 2012 advisory was followed by a drop in use and a reduction in slope, and the 2015 advisory had a more modest impact. Crude analysis suggests that domperidone may be associated with increased VT or sudden cardiac death (0.74 v. 0.37 per 10 000 person-years; difference per 10 000 person-years: 0.37, 95% confidence interval -0.67 to 1.41).

Interpretation: Postpartum domperidone use increased between 2004 and 2017, with prescribing attenuated after Health Canada advisories and a very low absolute rate of VT or sudden cardiac death. These findings suggest that Health Canada advisories affected prescribing; any potential increase in VT or sudden cardiac death with use of domperidone is small and could not be confirmed in this large study STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04024865.

Publication types

Observational Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antiemetics / adverse effects
Canada / epidemiology
Death, Sudden, Cardiac* / epidemiology
Death, Sudden, Cardiac* / etiology
Death, Sudden, Cardiac* / prevention & control
Domperidone / adverse effects*
Drug Utilization* / statistics & numerical data
Drug Utilization* / trends
Female
Humans
Interrupted Time Series Analysis
Lactation / drug effects
Lactation Disorders / drug therapy*
Off-Label Use / statistics & numerical data*
Postpartum Period*
Practice Patterns, Physicians' / statistics & numerical data
Pregnancy
Retrospective Studies
Risk Factors
Tachycardia, Ventricular* / chemically induced
Tachycardia, Ventricular* / diagnosis
Tachycardia, Ventricular* / epidemiology

Substances

Antiemetics
Domperidone

Associated data

ClinicalTrials.gov/NCT04024865

Grants and funding

DSE-146021/CIHR/Canada