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December 21, 2014

Domperidone – Risk of Cardiac Disorders

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Products include Domerid/Motilium

Domperidone is a propulsive agent and a dopamine antagonist with antiemetic properties. It is authorised for use in adults for the relief of nausea and vomiting, epigastric sense of fullness, upper abdominal discomfort and regurgitation of gastric contents, and in children for the relief of nausea and vomiting.

The risk of QTc prolongation and cardiac risk with domperidone was previously reviewed at EU level by the Pharmacovigilance Working Party (PhVWP) of the European Medicines Agency, with the product information updated to reflect the available data at that time (2008).

In 2010, two new epidemiological studies1, 2 were published concerning the risk of ventricular arrhythmia or sudden cardiac death (SCD) and a possible association with domperidone. A weak association with SCD was found. It was concluded that there is some evidence to support that, particularly at higher doses (>30mg/day), or in patients >60 years, domperidone may be associated with an increased risk of serious ventricular arrhythmias or SCD.

Spontaneous reports of suspected adverse reactions also suggest a potential association between domperidone and QT prolongation for non-parenteral routes of administration and an association with torsades de pointes (TdP), independently of the route of administration. Based on the assessment of the available data, the PhVWP recommended further updates to the product information for domperidone-containing products to reflect the current information on the risk of SCD, particularly in patients >60 years and in patients taking daily doses of >30mg/day and emphasised that domperidone should be used at the lowest effective dose in adults and children.

The PhVWP also recommended that the originator marketing authorisation holder should conduct an additional well-designed, high-powered epidemiological study on the association between domperidone and cardiac disorders, with particular emphasis on dose to further clarify this risk.

Healthcare professionals should be aware of these risks, closely adhere to the recommendations for use, and be particularly cautious when advising or treating patients who have existing prolongation of cardiac conduction intervals, particularly QTc, and those with significant electrolyte disturbances or underlying cardiac diseases such as congestive heart failure.

Healthcare professionals are reminded that co-administration with oral ketoconazole, erythromycin or other potent CYP 3A4 inhibitors that prolong the QTc interval should be avoided; for further details see the Summary of Product Characteristics (SPC) on www.imb.ie.

This information was recently communicated in a Direct Healthcare Professional Communication (DHPC) which is available on www.imb.ie. The Pharmaceutical Society of Ireland has also published guidance to support the safe supply of non-prescription medicines containing domperidone which can be located on www.thepsi.ie.

Suspected adverse reactions associated with the use of domperidone including cases of cardiac disorders should be reported to the IMB via the usual routes.

Key Message:

Some epidemiological studies have shown that domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death. The risk of serious ventricular arrhythmias or sudden cardiac death may be higher in patients >60 years or at daily oral doses >30mg. Domperidone should be used at the lowest effective dose in adults and children.

References

1- Van Noord C, Dieleman JP, van Herpen G, Verhamme K, Sturkenboom MC. Domperidone and ventricular arrhythmia or sudden cardiac death: a population-based case-control study in the Netherlands. Drug Saf. 2010; 33: 1003-1014.

2- Johannes C. et al. Pharmacoepidemiology and Drug Safety 2010; 19:881-888.