Summary Safety Review - Domperidone - Assessing the Potential Risks of Serious Ventricular Arrhythmias, QT Interval Prolongation and Sudden Cardiac Death

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2021-12-30

Product

Domperidone

Potential Safety Issue

Serious abnormal heart rhythm caused by abnormal electrical activity in the lower chambers of the heart (ventricular arrhythmia and QT interval prolongation) and sudden cardiac death.

Key Messages

  • Domperidone is authorized for sale in Canada to treat symptoms of slowed stomach emptying seen with certain gastrointestinal conditions, and to prevent symptoms, such as nausea and vomiting, caused by some drugs used to treat Parkinson's disease.
  • In 2021, Health Canada carried out a follow-up safety review to 1 previously completed in 2014.1 The current review was triggered by the publication of a Canadian study on the risk of heart effects with domperidone when used for lactation promotion, which is an off-label (non-authorized) use of the drug.2
  • Health Canada's review found no additional safety concerns with domperidone use and the risks of serious ventricular arrhythmias, QT interval prolongation or sudden cardiac death. The current product safety labelling (Canadian Product Monograph) for domperidone, related to these risks, is appropriate. No updates are needed at this time.
  • Health Canada will continue to monitor the safety of domperidone. Health Canada will also publish an Infowatch article to raise awareness and remind healthcare professionals of the cardiac risks and the maximum daily dose recommendations, as well as to encourage continued reporting of suspected safety issues with the use of domperidone.

Overview

In 2007, increased numbers of reports in the Canada Vigilance database prompted Health Canada to advise healthcare professionals to watch for drug interactions and risk factors that could result in changes to the electrical activity of the heart (QT prolongation) in patients using domperidone.3

In 2012, 2 studies showed an increased risk of serious abnormal heart rhythms (cardiac arrhythmias) in patients taking domperidone at doses exceeding 30 mg daily as well as in patients over 60 years of age. This prompted Health Canada to update the Canadian Product Monographs (CPMs) for domperidone to advise healthcare professionals to use the lowest possible dose of the drug, and to be cautious when prescribing it to patients at high risk of abnormal heart rhythms. At that time, Health Canada informed Canadians about this risk and changes to the CPMs.4

In 2014, 2 more safety reviews were carried out in response to new information received from a foreign regulator about domperidone safety and Health Canada’s consultation with Canadian healthcare professionals, respectively. The 2 reviews confirmed the risk of serious abnormal heart rhythms and sudden cardiac death related to domperidone use. As a result, the CPMs were further updated in 2015 to include a maximum daily dose recommendation, and new restrictions for use in patients with certain medical conditions or taking other drugs.

In 2021, Health Canada carried out a follow-up to the 2014 safety reviews of domperidone and serious ventricular arrhythmia, QT interval prolongation and sudden cardiac death. This latest safety review was triggered by the publication of a Canadian study2 on the risk of heart effects with domperidone when used for lactation promotion, an off-label use in Canada. The purpose of the current review was to consider recent information, for both the approved and off-label use, and determine if additional measures were warranted.

Use in Canada

  • Domperidone is a prescription drug authorized for sale in Canada to treat symptoms of slowed stomach emptying seen with certain gastrointestinal disorders, as well as to prevent symptoms, such as nausea and vomiting, caused by some drugs used to treat Parkinson's disease.
  • Domperidone was first marketed in Canada in 1985 and is available as a 10 mg tablet.
  • There were approximately 1.7 million prescriptions filled for domperidone in 2020, which represents approximately 120 million domperidone tablets.

Safety Review Findings

  • Health Canada reviewed the available information from searches of the Canada Vigilance databasea and published literature for both the approved and off-label use of domperidone.
  • Health Canada reviewed 15 cases (8 Canadian and 7 international) of serious ventricular arrhythmia, QT interval prolongation, and/or sudden cardiac death/cardiac arrest following the use of domperidone for both the approved and off-label use. Of the 15 cases, 6 (3 Canadian) were found to have a possible link with domperidone use. The remaining 9 cases (3 Canadian) did not have enough information to be further assessed.
  • The Canadian study that triggered this review found that the risk of cardiac side effects is very low in individuals using domperidone off-label to promote lactation.
  • Health Canada's safety review also looked at the scientific literature published since 2014, and did not find any new information about serious ventricular arrhythmia, QT interval prolongation, or sudden cardiac death following the use of domperidone for both the approved and off-label use.

Conclusions and actions

  • Health Canada's review of the available information found no new safety information related to the risks of serious ventricular arrhythmia, QT interval prolongation or sudden cardiac death for both the approved and off-label use of domperidone. As a result, no further updates to the CPMs are warranted.
  • Health Canada will publish an Infowatch article to raise awareness and remind healthcare professionals of the cardiac risks for both the approved and off-label use, and the maximum daily dose recommendations.
  • Health Canada encourages consumers and healthcare professionals to continue reporting any side effects related to the use of domperidone, and other health products, to the Canada Vigilance Program.
  • Health Canada will continue to monitor safety information involving domperidone, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action should new health risks be identified.

Additional information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international information and what is known about the use of domperidone both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. Summary Safety Review - Domperidone - Serious abnormal heart rhythms and sudden death (cardiac arrest) - Health Canada. Issued: 2015-01-27.
  2. Moriello C, Paterson JM, Reynier P, Dahl M, Aibibula W, Fisher A, et al. Off-label postpartum use of domperidone in Canada: a multidatabase cohort study. CMAJ Open. 2021 20210514;9(2):E500-9.
  3. Djelouah I, Scott C. Domperidone: heart rate and rhythm disorders. Canadian Adverse Reaction Newsletter 2007;17(1).
  4. Health Canada Public Communication: Domperidone maleate - Association with serious abnormal heart rhythms and sudden death (cardiac arrest). Posting date: March 7, 2012.

Footnotes

  1. Canadian reports can be accessed through the Canada Vigilance Online Database.

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