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

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.

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.

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.

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.

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.