Metoclopramide Tardive Dyskinesia Warnings Accompany New Tablets

A new orally disintegrating version of metoclopramide tablets, a generic variation of Reglan that Salix Pharmaceuticals, Ltd. received approval last week to begin marketing for treatment of diabetic gastroparesis and gastroesophageal reflux disease (GERD), will carry a “black box” warning about the risk of a serious movement disorder, known as tardive dyskinesia.

The FDA granted marketing approval for the new metoclopramide HC1-based MetozolV orally disintegrating tablets on September 8. They will be sold by Salix Pharmaceuticals, Ltd. in 5 mg and 10 mg strengths, with the same tardive dyskinesia warning the FDA required all metoclopramide drugs to carry earlier this year.

Metoclopramide tardive dyskinesia problems involve an involuntary movement disorder with symptoms that can include uncontrolled lip smacking, grimacing, repetitive chewing, rapid eye movements and blinking, pursing and puckering of the lips, tongue protrusion, impaired finger movements and involuntary movements in the body extremities. In some cases, the disorder disappears when the user stops taking the medication, but in other cases the condition is irreversible and permanent.

Originally formulated and marketed under the brand-name Reglan by Wyeth, which has since been discontinued, a number of manufacturers make generic metoclopramide products sold as tablets, oral solutions and injections.

In February 2009, the FDA required that manufacturers of all variations of the drug add a black box warning about the Reglan tardive dyskinesia risk, which is the strongest warning that can be placed on a prescription medication. The drug makers were also required to develop mitigation and risk evaluation strategies to help ensure patients are aware of the potential metoclopramide side effect.

Salix Pharmaceuticals’ new metoclopramide-based disintegrating tablets will include the warnings that users should avoid taking the medication for longer than 12 weeks except in rare cases where the therapeutic benefits outweigh the risks of developing tardive dyskinesia.

Prior to the FDA mandated warnings, metoclopramide drugs contained information that grossly underestimated the risk of tardive dyskinesia, according to Reglan lawsuits filed against Wyeth and generic drug makers. While the manufacturers previously indicated that the incidence of tardive dyskinesia from metoclopramide drugs was only 0.2%, the actual rate of occurrence is likely more than 100 times higher. In addition, estimates have suggested that before the black box warning was added, about 30% of all prescriptions for the medication were for more than 12 weeks, which greatly increased the risk.

In June, the U.S. Judicial Panel on Multidistrict Litigation denied a request to consolidate all federal metoclopramide lawsuits over tardive dyskinesia, so all of the cases are proceeding as individual claims in different districts throughout the country.