The FDA estimates that more than two million Americans use Reglan or its generic equivalent, metoclopramide. Reglan was approved for treatment of certain gastrointestinal disorders in 1979. In 2009, the FDA found that Reglan “poses a significant and serious public health concern” because it can cause tardive dyskinesia.

Tardive dyskinesia can be a devastating and totally disabling neurological condition characterized by involuntary and uncontrollable hands, feet, head, face and tongue movements, such as grimacing, lip smacking and tongue protrusions. There is no cure for tardive dyskinesia.

Approved indications for Reglan included prevention of nausea and vomiting associated with chemotherapy, diabetic gastroparesis and short term treatment (4 to 12 weeks) of GERD.

The manufacturers’ labelling before 2009 mentioned that extrapyramidal symptoms (aka EPS and are described as symptoms affecting the part of the motor system involved in the coordination of movement) could be a side effect of Reglan use and that such symptoms include, among others, acute dystonic reactions (muscle contractions cause twisting and repetitive movements or abnormal postures), involuntary movements of limbs, facial grimacing, torticollis (a twisted neck in which the head is tipped to one side), tongue protrusion, bulbar or slurred speech, motor restlessness and tardive dyskinesia. It also mentioned that the risk of developing tardive dyskinesia and the likelihood it would become irreversible was believed to increase with duration and dose.

Regarding the incidence of EPS, the label stated that acute dystonic reactions are the most common type of EPS associated with Reglan and that they occur in approximately 1 out of 500 patients. This implies that the risk of tardive dyskinesia, which is one of the several other types of EPS, is even less than 1/500.

However, beginning in 1989, a series of published studies has shown that prolonged use of Reglan causes tardive dyskinesia at an incidence of 20% to 30%. That is 1 to 1.5 out of every 5 prolonged use patients – which is far greater than the less than 1/500 indicated by the manufacturers’ label.

The manufacturers’ label did not convey the true magnitude of the risk of developing tardive dyskinesia, and how dramatically that risk increases after taking Reglan for more than 12 weeks. To compound the problem, many physicians failed to know or appreciate even the understated warnings. For example, the FDA’s own study found that a “substantial portion” of patients in that study had been prescribed Reglan for more than 90 days.

Unfortunately, it took an FDA directive in February 2009 to force the manufactures to strengthen their warnings and to get prescribing physicians to pay attention to them. The FDA required Reglan manufacturers to take several specific steps to alert physicians and patients about the serious risk posed by using Reglan for more than 12 weeks.

1. The FDA required manufacturers to initiate a Risk Evaluation and Mitigation Strategy, part of which requires distribution of a Medication Guide. The Medication Guide must include information about the serious risk of tardive dyskinesia and be given to all users each time a pharmacy dispenses Reglan.
2. The manufacturers were required to change their labelling to strengthen their "Warnings" section. The revised required Warnings section must state that:

a) “Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase with the duration of treatment and total cumulative dose” and

b) a published study found that in patients taking Reglan at least three months the incidence of tardive dyskinesia was 20%.

  3.  The manufacturers were also required to add the FDA’s strongest warning, a “Black Box” warning. The Black Box warning emphasizes that:

a) prolonged use (more than 12 weeks) of Reglan can cause tardive dyskinesia;

b) the risk of developing tardive dyskinesia increases with duration of use and cumulative dose; and

c) prolonged treatment should be avoided in all but rare cases.

Thus, the new warnings make clear that:

1. Reglan causes tardive dyskinesia;
2. the longer it is used  beyond 12 weeks, the more likely tardive dyskinesia will develop and the more likely it will be irreversible; and
3. when used beyong 12 weeks the incidence of tardive dyskinesia is a very frightening 1 out of 5 patients.

The tragedy here is not simply that these warnings came too late for the many Americans who have Reglan-induced tardive dyskinesia and will suffer from it for the rest of their lives, but that the information that could have prevented them from being stricken with this devastating condition in the first place has been available to Reglan’s manufacturers and prescribing physicians for so many years.

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