Domperidone

Breast-feeding women should not take the dopamine antagonist domperidone to induce or increase lactation, because the drug may put them at risk of developing a fatal cardiac arrhythmia, the Food and Drug Administration has warned.

Domperidone (Motilium) is a gastric motility agent widely used in Canada, New Zealand, Germany, Australia, Mexico, and South Africa to treat gastric reflux and nausea. The drug also increases prolactin production. Although unavailable in the United States and not approved for lactation induction in any country, domperidone is being used off label as a galactagogue, the FDA said. Internet sites that support breast-feeding promote the drug heavily; many of these sites also give readers tips about how to procure it in oral form.

In a talk paper issued last month, the FDA said that in other countries, intravenous administration of high doses of domperidone has been associated with cardiac problems, including irregular heartbeat and, in a few cases, fatal ventricular arrhythmia. Many of the deaths occurred in the mid-1980s, after which the intravenous form of the drug was withdrawn in Great Britain, said Gerald G. Briggs, B. Pharm., pharmacist clinical specialist, Women's Hospital, Long Beach (Calif.) Memorial Medical Center.

"When you see that kind of adverse effect in high IV doses, it's a cause for concern," Mr. Briggs said.

Serious adverse events with the oral form in the recommended dosage (10 mg, three to four times a day) are probably rare, but there is a possibility of toxicity in women who take additional doses or who metabolize the drug poorly, he said.

He added that nursing babies whose mothers take domperidone in the prescribed dosage are probably not at risk for adverse events.

Domperidone is listed as a drug "usually compatible with breast-feeding" in the American Academy of Pediatrics' 2001 policy statement. "The Transfer of Drugs and Other Chemicals Into Human Milk." Web sites supporting the drug's use are incorrect in touting the listing as an official endorsement of domperidone's safety, said Dr. Richard Gorman, chair of the AAP's Committee on Drugs.

"There are no case reports on this medication showing that nursing babies had any adverse events" from domperidone, Dr. Gorman said. "However, that's a long way from saying that breast-feeding women should take this drug. In fact, in countries where the drug is used, there are warnings on the label about using only with caution on breast-feeding women."

The policy and list are due to be updated in 2005, Dr. Gorman said. At that time, domperidone probably will be removed, as will cisapride, which is also on the current list. Cisapride was withdrawn from the U.S. market because of similar concerns about cardiac events.

"Domperidone possesses cardiac electrophysiological effects similar to those of cisapride and class III antiarrhythmic drugs," wrote Canadian researcher Benoit Drolet. "It prolongs cardiac repolarization at clinically relevant drug concentrations, and it should not be considered a no-risk alternative to cisapride." Patients with hepatic or renal insufficiency, those who suffer from long-QT syndrome, and patients on multidrug regimens are at particular risk when taking domperidone, he said (Circulation 102[16]:1883-85, 2000).

Using domperidone to induce lactation isn't worth risking potential complications, especially since an approved drug, metoclopramide (Reglan), effectively stimulates milk production without the possibility of cardiac problems. Dr. Gorman said.

But some breast-feeding advocates say metoclopramide has serious side effects, including depression and muscle spasm, that aren't seen with domperidone. Metoclopramide has been linked to severe depression and suicidality and is contraindicated in women with a history of depression, according to the prescribing information. La Leche League International gives information about domperidone on its Web site, but plainly states that the drug is not approved in the United States and is used off label as a galactagogue.

"We are very concerned about the FDA warning," said Katy Lebbing, spokesperson for La Leche League. "Domperidone is heavily used in the lactation community, and we know it has helped a lot of mothers increase their milk."

Statements on other breast-feeding support Web sites charge that the domperidone warning is politically motivated and that rival drug companies are lobbying to keep it out of the United States. Dr. Thomas Hale, professor of pediatrics at Texas Tech University, Lubbock, and author of "Medications and Mother's Milk," a book recommended by La Leche League, said that domperidone is safe and effective.

The FDA "wants to stop the importation of all drugs, particularly those used by the elderly, and now the breast-feeding mother," Dr. Hale wrote on his Web site. "I do not propose to advise you as to what you should do, but as for me, I simply choose to ignore them and their advice."

Breast-feeding advocates who staunchly support the use of domperidone for lactation are ignoring the facts, Dr. Gorman said. "We are pro-breast-feeding, but we're also pro-healthy mother."

To reduce the availability of domperidone in this country, the FDA also sent letters to six U.S. pharmacies that import the drug for use in compounding. The letters warned that all drugs with domperidone are unapproved and violate the federal Food, Drug, and Cosmetic Act. These companies have been ordered to cease using domperidone in any preparation.

BY MICHELE G. SULLIVAN

Mid-Atlantic Bureau

COPYRIGHT 2004 International Medical News Group
COPYRIGHT 2004 Gale Group