Drug Safety Update

Volume 5, Issue 10 May 2012

Latest advice for medicines users

This article has been superseded

Please see the most recent advice published in May 2014.

Domperidone: small risk of serious ventricular arrhythmia and sudden cardiac death

Article date: May 2012
Summary
Some epidemiological studies have shown that domperidone may be associated with a small increased risk of serious ventricular arrhythmia or sudden cardiac death. These risks may be higher in patients older than 60 years and in patients who receive daily oral doses of more than 30 mg. Non-prescription domperidone products are not recommended for use in patients with underlying cardiac disease, without medical supervision.
Domperidone is a dopamine antagonist with antiemetic properties. In the UK, it is available as a prescription-only medicine (maximum oral dose 80 mg) for the indications of nausea and vomiting, epigastric sense of fullness, upper abdominal discomfort, and regurgitation of gastric contents in adults. It is also available without a prescription in pharmacies at lower doses (daily dose 10 mg, maximum dose 40 mg) for the indications of minor gastrointestinal symptoms and nausea and vomiting in patients aged 16 years or older. The duration of non-prescription treatment should not exceed 2 weeks.

Cardiovascular risks

QTc prolongation and ventricular arrhythmia are known cardiac risks for all domperidone-containing products. A recent Europe-wide review of the available data found that domperidone may be associated with a small increased risk of serious ventricular arrhythmia or sudden cardiac death, especially in patients older than 60 years and in patients receiving daily oral doses of more than 30 mg. The Commission on Human Medicines has advised non-prescription domperidone products are not recommended for use in patients with underlying cardiac disease, without medical supervision.

Findings from epidemiology studies

Four epidemiology studiesVan Noord C, et al. Drug Saf 2010; 33: 1003–14 Johannes C, et al. Pharmacoepidemiol Drug Saf 2010; 19: 881–88 Straus SM, et al. Eur Heart Journal 2005; 19: 2007–12 De Bruin ML, et al. Br J Clin Pharmacol 2007; 63: 216–23have reported on the relation between domperidone and either sudden cardiac death alone, or on serious ventricular arrhythmia and sudden cardiac death as a combined endpoint. The findings from the two most recent studies [1,2] are summarised below.

Van Noord and colleagues[1] looked at 1304 cases of sudden cardiac death and 13 480 matched controls, of which ten cases were currently exposed to domperidone. For current use of domperidone, the adjusted odds ratio (OR) for a risk of sudden cardiac death was 1.92 (95% CI: 0.78–4.73). Analysis by dose suggested a higher risk for patients prescribed domperidone at higher doses (>30 mg/day), although there were only 4 exposed cases in each group and the 95% confidence intervals overlapped: OR 11.4 (1.99–64.9) for patients prescribed >30 mg/day, compared with 0.99 (0.23–4.23) for patients receiving 30mg/day.

The study by Johannes and colleagues [2] was the largest and most robust study in terms of exposed cases and included 1608 cases and 6428 controls (proton pump inhibitor [PPI] users), of which there were 169 cases and 482 controls with current exposure to domperidone. Compared with users of PPIs, the OR for current domperidone exposure was 1.44 (1.12–1.86). Stratified analyses by age and sex suggested a slightly higher risk for patients older than 60 years (OR 1.47 [1.14–1.91]) compared with those younger than 60 years (OR 1.23 [0.32–4.76]), although the 95% confidence intervals overlapped.

In light of evidence of a risk of serious ventricular arrhythmia and sudden cardiac death, it is important that the following advice is adhered to:

Advice for healthcare professionals:

  • Domperidone should be used at the lowest effective dose
  • Non-prescription domperidone products are not recommended for use in patients with underlying cardiac disease, without medical supervision
  • Prescribers should exercise caution for patients who have: existing prolongation of cardiac conduction intervals (particularly QTc); significant electrolyte disturbances; or underlying cardiac diseases such as congestive heart failure, and patients who are known to be taking prescribed medicines for these conditions, particularly for patients older than 60 years and patients who receive daily oral doses of more than 30 mg
  • Domperidone should be avoided in patients who are taking concomitant medication known to cause QT prolongation (eg, ketoconazole or erythromycin)
  • Patients should be advised to seek prompt medical attention if symptoms such as syncope or tachyarrhythmias appear during treatment

Advice for patients:

  • Non-prescription domperidone products are not recommended if you have current heart problems, or have ever had heart problems, including heart failure, a previous heart attack, angina (chest pains), or heart rhythm disorders including a rapid or slow or irregular heartbeat.
  • Seek medical attention immediately if you experience symptoms such as an irregular heartbeat or fainting while taking any domperidone product

Further information:

BNF section 4.6 Drugs used in nausea and vertigo

Article citation: Drug Safety Update May 2012, vol 5 issue 10: A2

References

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Page last modified: 08 August 2014