FDA Calls for Boxed Warning for Metoclopramide

Abstract

The US Food and Drug Administration announced on February 24, 2009, that manufacturers of metoclopramide must add a boxed warning to their drug labels delineating the risk of its long-term or high-dose use. Chronic use of metoclopramide has been linked to tardive dyskinesia even after medications containing this drug have been discontinued. Metoclopramide is used for short-term treatment of gastroesophageal reflux disease in patients who have not responded to other therapies, and to treat diabetic gastroparesis. It is recommended that treatment not exceed 3 months. Manufacturers will be required to implement a risk evaluation and mitigation strategy, or REMS, to ensure that patients are provided with a medication guide that discusses this risk. “The FDA wants patients and health care professionals to know about this risk so they can make informed decisions about treatment,” said Janet Woodcock, MD, director of the FDA's Center for Drug Evaluation and Research in the agency's announcement. “The chronic use of metoclopramide therapy should be avoided in all but rare cases where the benefit is believed to outweigh the risk.” Current product labeling warns of the risk of tardive dyskinesia with chronic metoclopramide treatment. The development of this condition is directly related to the length of treatment and dosing. Those at greatest risk include the elderly, especially older women, and long-term users. Tardive dyskinesia is characterized by involuntary, repetitive movements of the extremities, lip smacking, grimacing, tongue protrusion, rapid eye movements or blinking, puckering and pursing of the lips, or impaired movement of the fingers. These symptoms are rarely reversible and there is no known treatment. However, in some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped, the agency notes. Metoclopramide is available in a variety of formulations including tablets, syrups, and injections. Names of metoclopramide-containing products include: Reglan Tablets, Reglan Oral Disintegrating Tablets, Metoclopramide Oral Solution, and Reglan Injection. More than 2 million Americans use these products. Recently published analyses suggest that metoclopramide is the most common cause of drug-induced movement disorders. An additional FDA analysis of study data showed that approximately 20% of patients who used metoclopramide took it for >3 months. The agency says it has also become aware of continued anecdotal reports of tardive dyskinesia in patients who used metoclopramide, the majority of whom had taken the drug for >3 months.