McNeil v. Wyeth

United States Court of Appeals
Fifth Circuit
F I L E D
August 22, 2006
Charles R. Fulbruge III
Clerk
In the
United States Court of Appeals
for the Fifth Circuit
_______________
m 05-10509
_______________
SUE C. MCNEIL,
Plaintiff-Appellant,
VERSUS
WYETH,
FORMERLY KNOWN AS
AMERICAN HOME PRODUCTS CORPORATION,
DOING BUSINESS AS A.H. ROBINS COMPANY, INC.,
Defendant-Appellee.
_________________________
Appeal from the United States District Court
for the Northern District of Texas
_________________________
Before KING, SMITH, and BENAVIDES,
Circuit Judges.
JERRY E. SMITH, Circuit Judge:
Sue McNeil appeals a summaryjudgment for
defendant Wyeth, a pharmaceutical company.
We reverse and remand.
I.
In August 2000, Dr. Eduardo Wilkinson pre-
scribed Reglan, whose generic name is meto-
clopramide, manufactured by Wyeth, to treat
McNeil’s symptoms of gastroesophagealreflux
disease (“GERD”). The prescription was for
six months, though the Food and Drug
Administration had approved the drug only for
use of no more than twelve weeks. There-
after, McNeil’s prescription was continued by
Dr. Roy Ragsdale for six months and then by
Dr. William Mania for two months.

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GERD is a disease whose expression ranges
from infrequent heartburn to frequent heartburn
accompanied by regurgitation. In severe cases
it can lead to a narrowing of the esophagus by
scarring.
Reglan is a “prokinetic” drug that helps con-
trol GERD by blocking dopamine receptors in
the brain and throughout the body, thus enhanc-
ing movement or contractions of the esopha-
gus, stomach, and intestines. Dopamine is a
chemical produced naturally by the human body
that sends signals from one nerve to the next.
Simple movements of muscles, such as moving
a finger, are controlled by what is known as the
pyramidal system. More coordinated muscle
movements, such as dancing or talking, require
fine motor control from the extrapyramidal
system.
Byblocking dopamine receptors, Reglan can
affect the extrapyramidal system by causing
extrapyramidal symptoms (“EPS”), which “are
a group of adverse drug reactions referred to
generally as extrapyramidal symptoms because
of the involvement of the extrapyramidal ner-
vous system.”1 The clinical pharmacology
section of Reglan’s FDA-approved label ex-
plains that, like other “dopamine antagonists”
such as phenothiazines, Reglan “may produce
extrapyramidal reactions, although these are
comparatively rare.”
Tardive dyskinesia is a particularly severe
form of EPS characterized by grotesque invol-
untary movements of the mouth, tongue, lips,
and extremities, involuntary chewing move-
ments, and a general sense of agitation. Reg-
lan’s label warned that Reglan may produce
tardive dyskinesia.
In October 2001, about fourteen months af-
ter she started taking Reglan, McNeil was ad-
mitted to an emergency room complaining of
shortness of breath, anxiety, and an involun-
tary “chewing motion” of her mouth. The
nurse who first treated McNeil noted that she
was also fidgeting, appeared nervous, and had
an unsteady gait. The emergency room physi-
cian who later examined McNeil confirmed
these observations and diagnosed EPS, likely
occasioned by exposure to Reglan.
McNeil’s primary care physician confirmed
this diagnosis, discontinued Reglan, and pre-
scribed a replacement drug. When McNeil’s
EPS symptoms failed to improve with time,
she consulted a neurologist and two medical
specialists in movement disorder; all three con-
cluded that McNeil suffers from Reglan-in-
duced tardive dyskinesia in addition to Reglan-
induced EPS.
II.
McNeil sued Wyeth in state court. Her
complaint alleged that Wyeth had failed ade-
quately to warn physicians and consumers of
the increased risk of tardive dyskinesia that
accompanies long-term use of Reglan. McNeil
argued that Wyeth’s failure to warn rendered
the inherently unsafe product unreasonably
dangerous. Further, McNeil alleged that the
Reglan label was misleading as to the risk of
tardive dyskinesia and failed adequately to
warn about the increase in risk associated with
exposure to the drug for more than twelve
weeks.
Wyeth removed to federal court pursuant to
28 U.S.C. § 1332(a)(1). Both parties consent-
ed to decision by a magistrate judge, whom we
therefore refer to as the “district court.”
Wyeth moved for summary judgment, 1 Windham v. Wyeth Lab., Inc., 786 F. Supp.
607, 612 (S.D. Miss. 1992).

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which the court granted, concluding that the
Reglan label was “adequate as a matter of law”
because it “specifically mentions the circum-
stances complained of . . . .” More specifically,
the court noted that the label
specifies that the drug is intended for
short-term use of 12 weeks or less, warns
against the potential risk of tardive dys-
kinesia and other movement disorders,
and discloses that the risk of developing
tardive dyskinesia is highest among elder-
ly women and increases with the duration
of treatment and the total cumulative
dose. The label also describes the possi-
ble symptoms associated with movement
disorders caused by the drugSSthe very
symptoms of which plaintiff complains.
Therefore, the court concluded that Wyeth
was entitled to summary judgment on McNeil’s
marketing defect claims. In an additional para-
graph, the court stated that “Wyeth is entitled
to summary judgment on plaintiff’s design de-
fect claims.” McNeil appeals only the failure-
to-warn claims.
III.
Summary judgment is proper “if the plead-
ings, depositions, answers to interrogatories,
and admissions on file, together with the affi-
davits, if any, show that there is no genuine is-
sue as to any material fact and that the moving
party is entitled to a judgment as a matter of
law.” FED. R. CIV. P. 56(c). Disputes about
material facts are genuine “if the evidence is
such that a reasonable jury could return a ver-
dict for the nonmoving party.” Anderson v.
Liberty Lobby, Inc., 477 U.S. 242, 248 (1986).
We review the district court’s decision de novo.
Skotak v. Tenneco Resins, Inc., 953 F.2d 909,
912 (5th Cir. 1992). The evidence and infer-
ences from the summary judgment record must
be viewed in the light most favorable to the
nonmovant. Minter v. Great Am. Ins. Co.,
423 F.3d 460, 465 (5th Cir. 2005).
IV.
Texas, like most jurisdictions, has adopted
section 402A of the Restatement of Torts for
product liability claims. Nobility Homes, Inc.
v. Shivers, 557 S.W.2d 77, 79-80 (Tex. 1977).
Under that section, “[i]f a product is unreason-
ably or inherently dangerous, a warning is re-
quired.” Gravis v. Parke-Davis & Co., 502
S.W.2d 863, 870 (Tex. Civ. App.SSCorpus
Christi 1973, writ ref’d n.r.e.) (citing RE-
STATEMENT (SECOND) OF TORTS § 402A
(1965)).
Texas law generallyholds that the adequacy
of a product’s warning is a question of fact to
be determined by the jury. Williams v. Upjohn
Co., 153 F.R.D. 110, 114 (S.D. Tex. 1994);
Alm v. Aluminum Co. of Am., 717 S.W.2d
588, 591-92 (Tex. 1986)). In prescription
drug cases involving the learned intermediary
doctrine, however, when “a warning specifi-
cally mentions the circumstances complained
of, the warning is adequate as a matter of
law.” Rolen v. Burroughs Wellcome Co., 856
S.W.2d 607, 609 (Tex. App.SSWaco 1993,
writ denied).2
McNeil argues that the district court’s re-
liance on Rolen to find adequacy as a matter of
law is inapposite. We agree. Although Reg-
lan’s label mentions the conditions of which
McNeil complains, McNeil’s claim, unlike the
2 In Alm the court also cited with approval de-
cisions from Texas appellate courts that have
adopted and applied the learned intermediary doc-
trine in cases involving a drug manufacturer’s duty
to warn about the potential hazards of prescription
drugs.

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claim of the plaintiff in Rolen, is not that the
warning is inadequate because her condition
was not mentioned. Rather, her argument is
that the label is misleading as to the risk level
for developing the condition.
We are aware of no Texas case allowing ad-
equacy as a matter of law in such situations,
and therefore we apply the default Texas rule
that adequacy questions go to the jury. Our
position is consistent with Texas law and the
Restatement of Torts, which Texas courts fol-
low, because, as the district court recognized,
even in the context of a learned intermediary,
“‘if the warning to the intermediary is inade-
quate or misleading, the manufacturer remains
liable for injuries sustained by the ultimate
user.’”3
Warning the learned intermediary of a much
lower risk than the actual risk could render the
warning not just misleading, but ineffective.
When the risk described on the label is so low
as to induce a doctor to undertake the risk, had
he not done so if he were warned of the real
risk, we cannot say that no reasonable jury
could conclude that a warning was inadequate.
Thus, if the manufacturer decides to label a risk
as “comparatively rare” and also to provide a
numerical quantification of that risk, that num-
ber must be within a certain degree of accur-
acy.4
V.
The issue therefore is whether there is a
genuine issue of material fact as to whether the
label was misleading. This must be viewed in
terms of significant differences between the
disclosed risk and the actual risk of developing
EPS and tardive dyskinesia, with use longer
than twelve weeks.
A.
Wyeth argues that it does not have a duty
to warn about risks of use longer than twelve
weeks because the label clearly states that the
drug is indicated for treatment for no more
than that duration. Thus, not only would such
a warning be superfluous, but it would also be
improper, because Wyeth allegedly cannot tell
a medical professional how to exercise profes-
sional judgment on whether a drug should be
used longer than the period approved by the
FDA. We disagree.
Wyeth was, or should have been, aware
that Reglan was prescribed routinely for long-
term use. Plaintiff’s expert, Dr. Thompson,
testified that by 1988 Wyeth had its “own mar-
ket data that 84 percent of people” were using
Reglan long-term. In 1992, an article by Dr.
Ron Stewart and others drew attention to the
common practice of long-term treatment with
metoclopramide. The study involved 4,515
elderly patients at the Florida Geriatric Re-
3 Wyeth-Ayerst Lab. Co. v. Medrano, 28 S.W.3d
87 (Tex. App.SSTexarkana 2000, no writ) (citing
Alm, 717 S.W.2d at 591); see also Bristol-Myers
Co. v. Gonzales, 561 S.W.2d 801 (Tex. 1978);
Crocker v. Winthrop Labs., 514 S.W.2d 429 (Tex.
1974).
4 We do not mean to suggest that de minimis dif-
ferences in risk would send the adequacy question to
the jury, but when the differences in risk are signifi-
(continued...)
4(...continued)
cant, their potential misleading impact is a question
for the jury. Other courts have also recognized that
warnings that are “unreasonably diluted” may be
misleading and thus inadequate. See Salmon v.
Parke, Davis & Co., 520 F.2d 1359 (4th Cir.
1975) (deciding that although a specific condition
was mentioned in the label, “[c]omparing the com-
pany’s warning with [that suggested in] the article,
a jury could infer that Parke, Davis’ version was
unreasonably diluted”).

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search Program. Of the patients who reported
using metoclopramide, 32% had used it for
more than one year. This led the authors to
conclude that long-term treatment with meto-
clopramide is “quite common” and that other
prescription drugs were effective and safer for
treating GERD:
The routine use of metoclopramide for
gastroesophageal reflux should be ques-
tioned in light of the availability of safer,
more effective drugs such as hista-
mine-receptor blocking agents cimetidine
and ranitidine, and omeprazole. The
long-term efficacy and symptomatic ben-
efit of metoclopramide have not been
documented.
Because the widespread long-term use of
Reglan suggests that Wyeth’s indication for use
for no more than twelve weeks was widely dis-
regarded, a jury could infer that Wyeth’s warn-
ing was ineffective and thus inadequate. There-
fore, McNeil’s suggested additional warning
about long-term use would not be superfluous.
Moreover, the FDA regulations require a
manufacturer to inform a medical professional
precisely how to exercise his professional judg-
ment in certain circumstances. The “Contraindi-
cations” regulation requires that ‘[u]nder this
section heading, the labeling shall describe
those situations in which the drug should not be
used because the risk of use clearly outweighs
any possible benefit.’ 21 C.F.R. § 201.57(d)
(2000). Thus, the manufacturer must tell the
physician when the drug should not be used if
“the risk of use clearly outweighs any possible
benefit.”
One of McNeil’s experts testified that the
label should have indicated that use of Reglan
for longer than twelve weeks was contraindi-
cated (absent compelling circumstances). Wy-
eth’s former medical monitor for Reglan also
testified similarly by agreeing that “Reglan
should not be prescribed for long-term therapy
for GERD because the side effects are too
dangerous and because its efficacy in longer
term use has not been established.”
In sum, because the widespread long-term
use of Reglan suggests that Wyeth’s indication
for use for not more than twelve weeks was
widely disregarded, a jury could infer that the
warning was ineffective and therefore inade-
quate. It follows that Wyeth had a duty, under
Texas law, adequately to warn the learned in-
termediary of known risks with long term use
and not to be misleading as to that risk.
B.
Because Wyeth advertised that the risk of
developing EPS is “comparatively rare,” or
that it is 0.2% for short term use, just noting
that the risk is higher for long-term use may
not put a physician on notice that certain stud-
ies have found that the risk could be a hundred
times higher.5 That is, because the advertised
risk is negligibly low, the mere statement that
the risk increases with use does not put a
5 An 1989 study by Dr. Lucinda Miller and Dr.
Joseph Jankovic looking at 1,031 patients conclud-
ed that the prevalence of metoclopramide-induced
movement disorders is probably greater than
Wyeth’s estimate of 1 in 500. An article published
by Dr. Linda Ganzini and others in 1993 described
that 29% of the patients in a case-control study
exposed to metoclopramide met the case definition
of tardive dyskinesia. The average duration of
exposure to the drug was 2.6 years. Another
case-control study conducted by Dr. Daniel Sewell
in 1994 found that 27% of the patients exposed to
metoclopramide for longer than thirty days met the
case definition of tardive dyskinesia.

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physician on notice that the increase in risk is of
a completely different order of magnitude and
class of risk. Thus, a jury could find that the
risk of developing EPS from long-term use was
not just higher, but that it was “significantly”
higher, and that the label was therefore mislead-
ing and inadequate.
Wyeth argues, however, that it was not re-
quired to update its label, because the studies
indicating that the risk for long-term use could
be a hundred times higher showed mere associ-
ation with a disease, not necessarily causation.
Thus, Wyeth argues, because there could be a
variety of other factors responsible for the “as-
sociation” found in these studies, that associa-
tion does not necessarily require a warning to
physicians. This argument, however, is contra-
dicted by the FDA regulations that require that
the labeling “be revised to include a warning as
soon as there is reasonable evidence of an asso-
ciation of a serious hazard with a drug; a caus-
al relationship need not have been proved.” 21
C.F.R. § 201.57(e) (emphasis added).
Of course, it does not immediately follow,
from the fact that Wyeth is required under fed-
eral law to warn physicians of a significant “as-
sociation” between tardive dyskinezia and long-
term use of Reglan, that Texas law requires the
same thing. Texas law, however, does not ab-
solve a manufacturer, as a matter of law, of a
duty to warn on grounds that no existing stud-
ies or clinical trials prove actual causation.
In Jordan v. Geigy Pharms., 848 S.W.2d
176 (Tex. App.—Fort Worth 1992, no writ),
the court observed that although the drug
manufacturer warned that cases of “significant
renal failure in patients receiving Voltaren have
been reported from postmarketing experience,
but were not observed in over 4,000 patients in
controlled clinical trials,” it had not warned of
the possibility of “acute renal failure.” Jordan,
848 S.W.2d at 182. In other words, even if
the clinical studies did not show significant
renal failure and thus, also did not show acute
renal failure, there was a genuine issue of
material fact on adequacy raised solely by
association evidence (anecdotal case reports,
not clinical trials).
McNeil’s expert, Dr. Thompson, also noted
that manufacturers frequently change their la-
bels and warn physicians of side effects based
on simple case reports, not on actual studies
showing causation. For example, a pharma-
ceutical company for which she was working
at the time (Eli Lily) inserted a warning that a
certain use of the drug Papaverine is contrain-
dicated based only on a few case reports of its
apparently causing heart attacks, and no epide-
miological or other studies showing causation.
She explained that the contraindication attract-
ed a lot of hate mail from physicians who had
practiced the off-label use, but that it had to be
done, and it took little time to do. This is not
to say that a manufacturer is always required
to change a label based on case reports; we
mention Thompson’s testimony only to coun-
ter Wyeth’s contention that manufacturers
never change labels based on case reports (as
distinguished from clinical trials) and that they
never tell physicians how to exercise their
judgment.
Thus, it is not uncommon for drug compa-
nies to do precisely what Wyeth claims it can-
not do: tell physicians that a certain use is con-
traindicated even if no clinical or epidemiologi-
cal studies exist that confirm causation or
degree of risk. Certainly, it is easier for a man-
ufacturer to make an off-label use contraindi-
cated when that use provides only a minimal
amount of sales from that drug as opposed to
when the off-label use provides the majority of

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its sales, as allegedly it is with Wyeth and Reg-
lan. But it is precisely this factSSthat off-label
use allegedly provided a majority of Wyeth’s
salesSSthat would create Wyeth’s duty to phy-
sicians not to be misleading about the risk of
long-term use.
Admittedly, the physician, in the exercise of
professional judgment, can disregard the warn-
ings or contraindications provided by the manu-
facturer. But then he does so at his own risk,
and most physicians are likely reluctant to do so
absent more concrete evidence about the bene-
fits of long-term use, evidence that is absent in
this case. Even Dr. Wilkinson, who initially in-
dicated that he would not have changed his
long-term prescription of Reglan even if he had
read the studies now cited by McNeil, acknowl-
edged that he would not have prescribed
Reglan for more than twelve weeks had Wyeth
provided a contraindication on Reglan’s label.
Therefore, we cannot say as a matter of law
that the peer-reviewed studies cited by McNeil
do not describe a significant risk about which
Wyeth should have warned Texas physicians.
Of course, Wyeth is free to argue, to a jury, its
view of the proper weight to be given to these
studies; it can also challenge (if still timely) the
admissibility of these peer-reviewed studies
under Daubert v. Merrell Dow Pharms., Inc.,
509 U.S. 579 (1993).
McNeil has also raised a genuine issue of
materialfact as to whether pharmacologicalevi-
dence should have alerted Wyeth about the
significantly increased risk from long-term use.
Under Texas law, causation is generally an is-
sue of fact. Lenger v. Physician’s Gen. Hosp.,
Inc., 455 S.W.2d 703, 706 (Tex. 1970). An
expert opinion is legally sufficient evidence to
establish a causal relationship between the con-
dition and the event. See Rodriguez v. Reeves,
730 S.W.2d 19 (Tex. App.—Corpus Christi
1987, writ ref’d n.r.e.).
McNeil’s expert, Dr. Thompson, testified
that the well-known, scientifically established
pharmacology of dopamine antagonists that
block a D2 dopamine receptor such as meto-
clopramide or schizophrenia medications (Hal-
dol and Thorazine) is to diminish the effects of
dopamine in the brain. The inability of dopa-
mine to produce its effects causes EPS (includ-
ing Parkinsonian side effects such as rigidity,
tremor, and dystonia, and the more severe
side-effect known as tardive dyskinesia),
because the extrapyramidal system needs
dopamine to function. Thompson also testi-
fied that these side-effects for metoclopramide
are “highly predictable,” given the function it
performs (blocking dopamine receptors) and
the known effects of other dopamine blockers:
[M]ost of [metoclopramide’s] side effects
are related to its action, which is, in fact,
blocking the dopamine effects in the brain
and elsewhere. And so what it does is to
produce the whole array of side effects that
we associate with dopamine blockers. And
in this sense, it’s really no different that any
so-called neuroleptics, the drugs that pro-
duce the calming effect in schizophrenia.
So it’s just like Thorazine or Haldol or any
of the other antipsychotics. It’s highly pre-
dictable that this would be its effect . . . .
Thompson testified that the propensity of
neuroleptics such as Thorazine and Haldol to
cause tardive dyskinesia was discovered about
twenty years after the beginning of the use of
Thorazine, that is, in the late 1970’s. She fur-
ther testified that the rate of developing tardive
dyskinesia with long term use of D2 receptor
blockers was 25%. Therefore, she found to be
misleading the label’s claim that like other

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“dopamine antagonists” such as phenothiazines
(which include Thorazine), Reglan “may pro-
duce extrapyramidal reactions, although these
are comparatively rare. As Thompson testified,
Most of the papers I’ve seen would give
about the same prevalence rate of tardive
dyskinesia in Metoclopramide long term and
Thorazine long-term. So [the label] would-
n’t be correct in terms of being compara-
tively rare . . . . 25 percent isn’t rare com-
pared to anything.
Therefore, we cannot say as a matter of law
that Reglan’s label was adequate even if it failed
to warn that the risk of developing tardive
dyskinesia was not “comparatively rare,” but
increased significantly with long-term use.
VI.
Under Texas law, a plaintiff who complains
“that a prescription drug warning is inadequate
must also show that the alleged inadequacy
caused her doctor to prescribe the drug for
her.” Porterfield v. Ethicon, Inc., 183 F.3d
464, 468 (5th Cir. 1999); accord Stewart v.
Jannssen Pharm., 780 S.W.2d 910, 912 (Tex.
App.—El Paso 1989, writ denied). In other
words, a plaintiff must show not only that a
warning was inadequate, but that it was a “pro-
ducing cause” of his injuries.
Wyeth is correct that although the district
court has not addressed this issue, the matter
was before the court, so we could affirm for
this reason if we were to find for Wyeth on this
question. We do not so decide, however, be-
cause there is a genuine issue of material fact as
to whether the label’s inadequacy caused Mc-
Neil’s doctor to prescribe the drug.
Wilkinson gave conflicting testimony. On
the one hand, he stated that he still would have
prescribed the drug had he known that the risk
was “significant,” but would have alerted the
plaintiff to that risk. On the other hand, he
testified that he would not have prescribed the
drug had its label stated that use for longer
than twelve weeks is contraindicated because
the risks are significant and the benefits have
not been proven. Therefore, McNeil has
raised a genuine issue of fact as to whether
Wilkinson would have prescribed the drug had
the label’s warning been adequate.
Moreover, because Wilkinson testified that
he was never informed of the significant risk of
tardive dyskinesia associated with long-term
Reglan use and that such information certainly
would have changed the “risk/benefit” analy-
sis” and the conversation he would have had
with McNeil about the risks, the inadequate
labeling could be a producing cause of the
injury even if Wilkinson had never testified
that he would not have prescribed Reglan had
a contraindication been inserted. Sworn testi-
mony from McNeil establishes that she was
never told of the significantly increased risk of
tardive dyskinesia with use of Reglan for
greater than twelve weeks and that, if she had
known of such a risk, she would not have
taken Reglan for longer than that.
The doctrine of the “learned intermediary”
presupposes that the physician will act as an
intermediary. This function includes discuss-
ing the cost-benefit ratio with the patient if
necessary. Where the physician would have
adequately informed a plaintiff of the risks of
a disease, had the label been sufficient, but fails
to do so on that account, and where the plain-
tiff would have rejected the drug if informed,
the inadequate labeling could be a “producing”
cause of the injury, because it effectively sabo-

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tages the function of the intermediary.6
We note that our discussion of “permissible
inferences is intended neither to define nor to
decide the issues in this case.” Salmon, 520
F.2d at 1364. It serves merely to illustrate our
reasons for concluding that summary judgment
is inappropriate. Reasonable minds can differ
on whether not mentioning that the increase in
risk for long-term use was significant would be
misleading. But this is precisely why that ques-
tion should go to the jury. The summary judg-
ment is REVERSED, and this matter is RE-
MANDED for further proceedings.
6 “[T]he mere presence of an intermediary does
not excuse the manufacturer from warning those
whom it should reasonably expect to be endangered
by the use of its product.” Alm, 717 S.W.2d at 591.
Instead, the issue “in every case is whether the
original manufacturer has a reasonable assurance
that its warning will reach those endangered by the
use of its product.” Id. Although usually the
manufacturer can rely on the “learned intermedi-
ary,” id., this reliance seems less reasonable where
the learned intermediary fails to pass necessary in-
formation to the patient because the manufacturer
has understated the degree of risk.

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