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Open Access

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 and Kristian B. Filion; for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators
May 14, 2021 9 (2) E500-E509; DOI: https://doi.org/10.9778/cmajo.20200084
Carolina Moriello
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.
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J. Michael Paterson
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.
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Pauline Reynier
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.
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Matthew Dahl
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.
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Wusiman Aibibula
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.
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Anat Fisher
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.
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John-Michael Gamble
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.
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I fan Kuo
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.
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Paul E. Ronksley
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.
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Brandace Winquist
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.
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Kristian B. Filion
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.
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  • Figure 1:
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    Figure 1:

    Flow diagram describing the construction of the study cohort across provinces, by pregnancy. *Patients were eligible to contribute multiple pregnancies to the study cohort. †The exclusion of observations with less than 365 days of health coverage was predominantly driven by Ontario, where the study population was restricted to patients receiving social assistance. Patients excluded in this step in Ontario included those who did not receive social assistance for at least 365 days before conception.

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    Figure 2:

    Prevalence of domperidone use in the 6 months after delivery among postpartum patients in 5 Canadian provinces. Health Canada advisories regarding domperidone were issued in March 2012 and January 2015.

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    Figure 3:

    Interrupted time series analysis examining the impact of the 2012 Health Canada advisory on rates of initiation of domperidone in the 6 months immediately postpartum in 5 Canadian provinces. The dashed line represents the release of the 2012 Health Canada advisory. Note: CI = confidence interval.

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    Figure 4:

    Interrupted time series analysis examining the impact of the 2015 Health Canada advisory on rates of initiation of domperidone in the 6 months immediately postpartum in 4 Canadian provinces. Ontario was excluded from this analysis owing to insufficient data available post-advisory. The dashed line represents the release of the 2015 Health Canada advisory. Note: CI = confidence interval.

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    Table 1:

    Baseline characteristics of deliveries overall and by use of domperidone in the 6 months immediately postpartum*

    CharacteristicNo. (%) of deliveries†
    Overall
    n = 1 190 987
    Domperidone
    n = 137 401
    No domperidone
    n = 1 053 586
    Age, yr, mean ± SE28.6 ± 0.629.6 ± 0.428.5 ± 0.6
    Obesity‡22 549 (1.9)3221 (2.3)19 328 (1.8)
    Alcohol-related disorders27 340 (2.3)2266 (1.7)25 074 (2.4)
    Income quintile
     1 (lowest)267 188 (22.4)24 705 (18.0)242 483 (23.0)
     2233 098 (19.6)25 919 (18.9)207 179 (19.7)
     3218 305 (18.3)26 947 (19.6)191 358 (18.2)
     4223 515 (18.8)28 496 (20.7)195 019 (18.5)
     5 (highest)177 454 (14.9)23 423 (17.1)154 031 (14.6)
     Unknown71 427 (6.0)7911 (5.8)63 516 (6.0)
    Comorbidities
     Previous history of arrhythmia or conduction disorders28 582 (2.4)4047 (3.0)24 535 (2.3)
     Any insertion of a pacemaker or defibrillator234 (< 0.1)28 (< 0.1)183 (< 0.1)
     Hypertension66 828 (5.6)9658 (7.0)57 170 (5.4)
     Cardiomyopathy1193 (0.1)139 (0.1)1054 (1.0)
     Left ventricular hypertrophy159 (< 0.1)14 (< 0.1)143 (0.0)
     Heart failure2435 (0.2)330 (0.2)2105 (0.2)
     Ischemic heart disease12 384 (1.0)1956 (1.4)10 428 (1.0)
     Valvular heart disease2620 (0.2)327 (0.2)2293 (0.2)
     Diabetes65 651 (5.5)10 116 (7.4)55 535 (5.3)
     Depression157 761 (13.3)20 421 (14.9)137 340 (13.0)
    Pregnancy-related characteristics
     Multifetal gestation22 008 (1.9)5547 (4.0)16 461 (1.6)
     Parity ≥ 1
      No579 511 (48.7)87 614 (63.8)491 897 (46.7)
      Yes611 025 (51.3)49 773 (36.2)561 252 (53.3)
      Unknown451 (0.0)14 (0.0)437 (0.0)
     Cesarean delivery332 987 (28.0)49 579 (36.1)283 408 (26.9)
     Gestational age, wk, mean ± SE39 ± 0.238.6 ± 0.339.1 ± 0.2
      ≤ 37128 950 (10.8)21 132 (15.4)107 818 (10.2)
      38–42 (inclusive)1 061 930 (89.2)116 262 (84.6)945 668 (89.8)
      ≥ 43107 (0.0)6 (0.0)100 (0.0)
    Use of medications
     Antiarrhythmic drugs26 731 (2.2)4456 (3.2)22 275 (2.1)
     Statins2286 (0.2)366 (0.3)1920 (0.2)
     Antihypertensive medications41 499 (3.5)6915 (5.0)34 584 (3.3)
     Proton pump inhibitors63 432 (5.3)10 389 (7.6)53 043 (5.0)
     Antipsychotic medications18 990 (1.6)2486 (1.8)16 504 (1.6)
     Other medications with galactagogic effects32 607 (2.7)4652 (3.4)27 955 (2.7)
     Drugs with known risk of QT prolongation294 860 (24.8)42 866 (31.2)251 994 (23.9)
     Strong and moderate CYP3A4 inhibitors130 647 (11.0)18 051 (13.1)112 596 (10.7)
    • Note: CYP3A4 = cytochrome P450 3A4, SE = standard error.

    • ↵* Patients were permitted to contribute multiple observations to the study cohort.

    • ↵† Unless stated otherwise.

    • ↵‡ Defined using diagnostic codes for obesity (International Statistical Classification of Disease and Related Health Problems, 10th Revision code E66.x and International Classification of Diseases, 9th Revision code 278.0).

    • View popup
    Table 2:

    Rates of ventricular tachycardia, sudden cardiac death and all-cause mortality among postpartum patients in the 6 months immediately postpartum across the 5 participating provinces (2004–2017), by current use of domperidone

    VariableIncidence rate (95% CI)*Crude rate ratio (95% CI)Crude rate difference (95% CI)*
    Composite of VT or sudden cardiac death
     Current domperidone use0.74 (0.19 to 2.97)2.01 (0.47 to 8.60)0.37 (−0.67 to 1.41)
     No current domperidone use0.37 (0.24 to 0.57)1.00 (Ref.)0.00 (Ref.)
    VT
     Current domperidone use0.74 (0.19 to 2.97)3.66 (0.81 to 16.49)0.54 (−0.50 to 1.57)
     No current domperidone use0.20 (0.11 to 0.37)1.00 (Ref.)0.00 (Ref.)
    Sudden cardiac death
     Current domperidone use0.00 (0.00 to 0.00)—−0.18 (−0.30 to −0.07)
     No current domperidone use0.18 (0.10 to 0.34)1.00 (Ref.)0.00 (Ref.)
    All-cause mortality
     Current domperidone use1.11 (0.36 to 3.45)0.37 (0.12 to 1.15)−1.93 (−3.28 to −0.59)
     No current domperidone use3.05 (2.61 to 3.55)1.00 (Ref.)0.00 (Ref.)
    • Note: CI = confidence interval, Ref. = reference, VT = ventricular tachycardia.

    • ↵* Incidence rate and rate difference are expressed as event per 10 000 person-years. Event totals by treatment group are not reported owing to the presence of small cells (counts < 6).

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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
Apr 2021, 9 (2) E500-E509; DOI: 10.9778/cmajo.20200084

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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
Apr 2021, 9 (2) E500-E509; DOI: 10.9778/cmajo.20200084
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