Reglan & Tardive Dyskinesia Lawyer Blog

Expert Witness For Pliva Discusses Reglan Warning Label

In this report, an expert witness retained by Pliva expresses the opinion that Pliva's metoclopramide warning label was adequate.

9. However, because of how the FDCA was structured, companies that wanted to
market generic versions of drug products approved under NDAs after 1962, such as
Reglan brand of metoclopramide, would have had to duplicate the expensive animal
and clinical studies the innovator did, even though the patent protection had
ended. This situation had the consequence of providing a virtual monopoly for
drugs first approved after 1962, because generic drug manufacturers did not have
the financial resources to perform extensive clinical and animal studies and to
prepare and submit NDAs to the FDA. The Congress remedied this situation in 1984,
when the Hatch-Waxman amendments to the FDCA extended a simplified administrative
process the FDA used for generic versions of older drugs, called an Abbreviated
NDA (ANDA) to generic versions of drugs first approved after 1962. The public
policy arguments for the Hatch-Waxman amendments included the following:

Reglan Attorney For Wyeth Asks Court to Exclude Evidence Of Reglan Side Effects

This motion was filed in the Louisiana Reglan lawsuit of Tarver v. Wyeth.  The motion asks the court not to allow Dr. Daniel Sewell to testify about the association between Reglan and movement disorders like tardive dyskinesia.

On behalf of Wyeth, Mr. Reilly contacted Dr. Sewell in early 1999 to ask him about
his paper on Tardive Dyskinesia and to investigate his willingness to consult with
Wyeth on the Woodworth matter. Dr. Sewell informed Mr. Reilly that he was not
working with plaintiff's counsel in Woodworth and that he did not have any
conflicts that would prohibit him from working for Wyeth. Mr. Reilly eventually
scheduled an in-person meeting with Dr. Sewell. At their meeting, which took place
on or about April 27, 1999, Mr. Reilly and other counsel for Wyeth met with Dr.
Sewell for three-and-a-half hours. Dr. Sewell spent another hour-and-a-half
reviewing medical records and a videotape related to the plaintiff in Woodworth.

During this lengthy meeting, counsel for Wyeth shared confidential information
regarding the Woodworth case, including their thoughts on the merits of
plaintiff's claims and the adequacy of the Reglan(R) label. In the course of that
meeting, Dr. Sewell provided his assessment of plaintiff's condition; his thoughts
about the use of Reglan(R) for gastrointestinal disorders; his opinions about the
adequacy of the Reglan(R) label, especially in light of his paper on the use of
Reglan(R) in the VA center; and general defense strategies. It is important to
emphasize that the plaintiff in Woodworth was represented by the same attorney in
this case -- Mr. Ralph Pittle. Indeed, plaintiffs theories of liability in the
instant case are similar if not identical to those pursued in Woodworth by Mr.
Pittle.

From this point forward, Mr. Reilly and Wyeth reasonably believed that Wyeth had
established a confidential relationship with their new consultant, Dr. Sewell. In
fact, following this meeting, Dr. Sewell sent Mr. Reilly "an invoice for my
consultation with you and Stuart Gordon in San Diego." This invoice clearly
demonstrated that, from Dr. Sewell's perspective, a consultation had occurred. See
Affidavit of James R. Reilly in Support of Wyeth's Motion to Exclude Plaintiffs'
Expert Daniel Sewell at "Exhibit A." This confidential relationship was further
confirmed by Mr. Reilly's payment to Dr. Sewell for his services.

Government Report Discusses Metoclopramide Side Effects

This report was filed in the Louisiana Metoclopramide lawsuit entitled Tarver v. Wyeth.

Metoclopramide is a neuroleptic dopamine receptor antagonist, currently marketed
in the U.S. (Reglan(R)) for short-term therapy of gastroesophageal reflux and for
treatment of diabetic gastroparesis. In general, therapy with metoclopramide
tablets should not exceed 12 weeks in duration, as prolonged therapy and
cumulative dose may increase the risk of developing tardive dyskinesia. The aim of
this review is to assist in preparation for a forthcoming advisory committee
meeting on the approvability of Myzan(R), a combination of naproxen and
metoclopramide, for the acute treatment of migraine, by estimating both the use of
metoclopramide in the U.S. as well as the proportion of patients taking
metoclopramide for more than 90 days.

....

Over the ten-year period from 1995 to 2004, there was a two-fold increase in the
number of outpatient prescriptions dispensed for metoclopramide in the U.S. In
1995, the number of prescriptions dispensed for metoclopramide was almost 3.5
million. This number declined to less than 2 million prescriptions dispensed
annually from 1997 to 1999, and then increased abruptly in 2000 and reached over 7
million prescriptions dispensed during 2004. The increase in dispensed
prescriptions beginning in 2000 is likely due to the withdrawal of cisapride, a
treatment for severe nighttime heartburn, from the US. market in March 2000.
Almost 90% of the metoclopramide products dispensed were in an oral tablet dosage
form.

Over one-third of the annual visits in the U.S., in which metoclopramide was
mentioned, were made by patients ages 35-64 years old. Elderly patients (aged 65
years and older) accounted for about a third of the visits in which metoclopramide
was mentioned from 1995-1998, yet their proportions declined steadily in the
subsequent years. As opposed to the elderly population, visits in which
metoclopramide was mentioned in the pediatric population (aged 0-16 years)
increased steadily throughout the ten-year study period and constitute more than
30% of these visits in 2004. Visits in which metoclopramide was mentioned in
patients aged 17- 34 years remained steady. On average, over 55% of the annual
visits in which metoclopramide was mentioned were made by females.

During the last five years, from 2000 through 2004, more than 50% of
metoclopramide uses were for gastroenterology-related diagnoses. "Esophagitis"
(ICD-9 code 530.1) was ranked the most common diagnosis for metoclopramide
mentions, accounting for over 40% of metoclopramide mentions.

FDA Document Discusses Movement Disorders Associated With Metoclopramide

The following document was filed in the Louisiana lawsuit of Tarver v. Wyeth.  It discusses some concerns that the FDA had with metoclopramide and movement disorders.

Regarding the safety of MT100, my main concern relates to the extrapyramidal
adverse events known to be caused by metoclopramide.[FN3] Reglan labeling states
that extrapyramidal symptoms, mainly acute dystonic reactions, occur in
approximately 0.2% of patients receiving oral metoclopramide at doses between 30
to 40 mg per day. Dr. Prohaska notes that during the clinical development program
for MT100, there were two subjects reporting acute dystonic reactions, which
demonstrates the potential for extrapyramidal adverse events even at the dose (16
mg) of metoclopramide contained in MT 00. Akathisia has also been reported with
metoclopramide in the literature,[FN4] and metoclopramide-induced akathisia can
even apparently lead to suicide attempt, as reported in the literature.[FN5]