Reglan® Requires FDA Approved Black Box Label Warning

Tardive Dyskinesia is a debilitating and untreatablecondition caused by extended use, or high dosages of neuroleptic drugs. Symptomsof tardive dyskinesia are primarily involuntary muscle movements includingtwitching and jerking of the extremities, lip smacking, tongue protrusion, lippursing or puckering, rapid eye movements, repetitive blinking, and impairedfinger movements. While these symptoms may decrease after a patient stopstaking the causative drugs, the condition is untreatable and the symptomsrarely reverse completely.

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

Why FDA changed thelabel requirements

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

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

Other requirements

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

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