Reglan® Requires FDA Approved Black Box Label Warning

Tardive Dyskinesia is a debilitating and untreatable condition caused by extended use, or high dosages of neuroleptic drugs. Symptoms of tardive dyskinesia are primarily involuntary muscle movements including twitching and jerking of the extremities, lip smacking, tongue protrusion, lip pursing or puckering, rapid eye movements, repetitive blinking, and impaired finger movements. While these symptoms may decrease after a patient stops taking the causative drugs, the condition is untreatable and the symptoms rarely reverse completely.

Metoclopramide (the active ingredient in Reglan®) is the most common drug known to cause tardive dyskinesia. Metoclopramide is a drug used to treat gastrointestinal disorders such as heartburn and esophageal reflux disease, and some neurological and psychiatric disorders. Metoclopramide is an ingredient in several formulations of Reglan®, including tablets and injection, and is also available in a generic tablet and oral solution.

Why FDA changed the label requirements

Although Reglan® has always placed warnings about the risk of tardive dyskinesia on its packaging, the FDA has issued a notice that the degree of risk was not known at the time the

“Abbreviated New Drug Application” (ANDA) was filed. Since that time the increasing number of cases of tardive dyskinesia associated with patients taking Reglan® or metoclopramide have warranted an FDA order for the manufacturer to provide a “black box” label warning consumers and health care professionals of the risks of developing tardive dyskinesia as a result taking this drug in high doses or for periods exceeding 90 days. In addition to the dosage and length of treatment other increased risk factors include female gender, advanced age, and the total cumulative dose.

Other requirements

In addition to the black box warning label, the manufacturer must submit a “Risk Evaluation and Mitigation Strategy” (REMS), a plan outlining in detail exactly how they will notify health care providers of the risks of this drug and the need to evaluate the risks in relation to the benefits of using it. Among the other requirements of a REMS are information needed to make this risk to benefit assessment, a medication guide, and a plan to inform health care providers that it is necessary for them to inform the patients of these risks in an effort to avoid adverse outcomes.

Over two million Americans take products containing metoclopramide for gastric problems. Patients with gastric reflux disease and diabetic gastroparesis, in which the gastric contents empty slowly into the intestines benefit from the drugs’ ability to increase stomach muscle movement, thus avoiding reflux of stomach contents into the esophagus.