Use of Domperidone and Risk of Serious Cardiac Events in Postpartum Women (Q16-10)

Use of Domperidone and Risk of Serious Cardiac Events in Postpartum Women (Q16-10)

Q16-10

Overview

What is the issue?
  • Domperidone, an antiemetic and prokinetic drug, is often used off-label to promote lactation among postpartum women with insufficient breast milk supply.
  • Safety concerns have been raised that domperidone could potentially increase the risk of sudden cardiac death (SCD) and ventricular tachyarrhythmia (VT), with Health Canada advisories in 2012 and 2015.
What is the aim of the study?
  • This study evaluated the impact of the Health Canada advisories on the use of domperidone and assessed its safety in postpartum women.
How was the study conducted?
  • CNODES conducted a retrospective cohort study using administrative health databases from five Canadian provinces with records of close to 1.2 million postpartum women.
  • Domperidone utilization postpartum, rates of initiation, and average dose and duration were estimated. The impacts of the 2012 and 2015 advisories were assessed via interrupted time-series analysis.
  • Crude rate ratios and differences were estimated for the composite endpoint (VT or SCD) and secondary outcomes (VT, SCD, and all-cause mortality) for use versus non-use of domperidone, postpartum.
What did the study find?
  • The cohort included 1,190,987 pregnancies, with 11.5% exposed to domperidone.
  • Domperidone use increased among postpartum women between 2004 and 2017, although variations existed across provinces.
  • The 2012 Health Canada safety advisory was followed by a reduction in prescribing across provinces, whereas the 2015 advisory had a more modest impact on prescribing practices, despite its stronger content.
  • A crude analysis suggests that domperidone may increase the risk of the composite endpoint of VT or SCD (rate ratio: 2.01; 95% CI: 0.47, 8.60; rate difference per 100,000 person-years: 3.7; 95% CI: -6.7, 14.1). A safety analysis with statistical adjustment was not feasible due to the rarity of these adverse events.
Implications
  • Domperidone use among postpartum women increased substantially between 2004 and 2017.
  • Domperidone users had a higher frequency of cardiac death or ventricular tachyarrhythmia than nonusers. Due to the rarity of these events and lack of statistical adjustment, these results should be interpreted with caution.
Key messages
  • Domperidone use among postpartum women increased substantially between 2004 and 2017.
  • Domperidone users had a higher frequency of cardiac death or ventricular tachyarrhythmia than non-users. Due to the rarity of these events and lack of statistical adjustment, these results should be interpreted with caution.

Manuscripts

Ou LB; Moriello C; Douros A; Filion KB. Domperidone and the Risks of Sudden Cardiac Death and Ventricular Arrhythmia: A Systematic Review and Meta-Analysis of Observational Studies. British Journal of Clinical Pharmacology. Br J Clin Pharmacol. 2021 oct;87(10):3649-3658.

Moriello C; Paterson JM; Reynier P, Dahl M; Aibibula W; Fisher A; Gamble JM; Kuo IF; Ronksley PE; Winquist B; Filion KB for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Off-label postpartum use of domperidone in Canada: a multidatabase cohort study. CMAJ Open. 2021 May 14; (9)2: E500-E509.

Presentations

Project Team

Project Lead
Kristian Filion PhD
Methods Lead
Steering Committee Liaison
Michael Paterson MSc
Lead Analyst
Pauline Reynier Msc
Lead Analyst
Matthew Dahl BSc
Staff Scientist
Wusiman Aibibula PhD
Research Assistant
Carolina Moriello MSc
Research Assistant
Site Investigator
Brandace Winquist
Saskatchewan
Site Investigator
John-Michael Gamble BSc (Pharm), MSc, PhD
Ontario
Site Investigator
I Fan Kuo ACPR, MSc, PharmD
Manitoba
Site Investigator
Anat Fisher MD, PhD
British Columbia
Site Investigator
Paul Ronksley PhD
Alberta
Analyst
Xinya Lu PhD
Saskatchewan
Analyst
Fangyun Wu MSc
Ontario
Analyst
Matthew Dahl BSc
Manitoba
Analyst
Richard Morrow Ma, PhD Candidate
British Columbia
Analyst
Jianguo (James) Zhang MSc
Alberta