Domperidone Under Scrutiny in Europe Due to Cardiac Risks

March 08, 2013

European Union (EU) drug regulators announced yesterday that they have begun a review of domperidone, an antiemetic, because of concerns about adverse cardiac events, including QT prolongation and arrhythmias.

Domperidone-containing antiemetics, sold under brand names such as Motilium (Janssen), Mirax (Berlin), and Domper (Opalia, YSP, and Yung Shin), are widely available over the counter or by prescription in a number of European countries. The drugs also have been used on an off-label basis to increase lactation in breast-feeding mothers.

The US Food and Drug Administration (FDA) has not approved domperidone for any indication. In 2004, the FDA warned clinicians and breast-feeding mothers not to use domperidone to boost milk production because of the risk for adverse events. The agency cited reports of cardiac arrhythmias, cardiac arrest, and sudden death in patients receiving an intravenous form of domperidone that has been discontinued in several countries. However, the European Medicines Agency (EMA) — the EU equivalent of the FDA — continued to receive reports of these adverse events with other forms of the drug.

The FDA noted in 2004 that breast-feeding women in the United States were buying the drug from Internet pharmacies and US compounding pharmacies. The FDA sent warning letters to 6 such compounding pharmacies about the illegal trade in domperidone. A similar letter was issued in 2010 to a compounding pharmacy in Virginia. However, Internet pharmacies still continue to advertise the drug.

The EMA said yesterday that it began its review of domperidone at the request of drug regulators in Belgium, who learned of new cases of cardiotoxicity. Those regulators have proposed that the drug be contraindicated for patients with QT prolongation, significant electrolyte disturbances, or underlying cardiac diseases such as congestive heart failure.

The EMA said that its Pharmacovigilance Risk Assessment Committee will study domperidone-containing drugs, assess whether their benefits outweigh their risks, and recommend possible regulatory action, which could include withdrawing the drugs from the market or revising their label instructions.

More information is available on the EMA Web site.