United States Court of Appeals

Fifth Circuit

FILED

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:

SueMcNeil appeals a summaryjudgmentfor

defendant Wyeth, a pharmaceutical company.

We reverse and remand. 

I.

InAugust 2000, Dr.Eduardo Wilkinsonprescribed Reglan, whose generic name is metoclopramide, 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. Thereafter, McNeil’s prescription was continued by

Dr. Roy Ragsdale for six months and then by

Dr. William Mania for two months. 
2

GERD is a disease whose expression ranges

frominfrequent heartburnto 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 control GERD by blocking dopamine receptors in

the brain and throughout the body, thus enhancing movement or contractions of the esophagus, stomach, and intestines. Dopamine is a

chemicalproduced naturallybythe 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 asthe

pyramidal system. More coordinated muscle

movements, such as dancing or talking, require

fine motor control from the extrapyramidal

system. 

Byblocking dopamine receptors,Reglancan

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 nervous system.”1 The clinical pharmacology

section of Reglan’s FDA-approved label explains 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 involuntary movements of the mouth, tongue, lips,

and extremities, involuntary chewing movements, and a general sense of agitation. Reglan’s label warned that Reglan may produce

tardive dyskinesia. 

InOctober 2001, about fourteenmonths after she started taking Reglan, McNeil was admitted to an emergency room complaining of

shortness of breath, anxiety, and an involuntary “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 physician 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 prescribed a replacement drug. When McNeil’s

EPS symptoms failed to improve with time,

she consulted a neurologist and two medical

specialistsinmovement disorder; allthree concluded that McNeil suffers from Reglan-induced tardive dyskinesia in addition to Reglaninduced EPS. 

II.

McNeil sued Wyeth in state court. Her

complaint alleged that Wyeth had failed adequately to warn physicians and consumers of

the increased risk of tardive dyskinesia that

accompanieslong-termuse ofReglan. 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. 

Wyethremoved to federal court pursuant to

28 U.S.C. § 1332(a)(1). Both parties consented to decision by a magistrate judge, whomwe

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). 
3

which the court granted, concluding that the

Reglan label was “adequate as a matter of law”

because it “specifically mentions the circumstances complained of . . . .” More specifically,

the court noted that the label 

specifies that the drug is intended for

short-termuse of 12 weeks or less, warns

against the potential risk of tardive dyskinesia and other movement disorders,

and discloses that the risk of developing

tardive dyskinesia is highest among elderlywomen and increases with the duration

of treatment and the total cumulative

dose. The label also describes the possible 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 paragraph, the court stated that “Wyeth is entitled

to summary judgment on plaintiff’s design defect claims.” McNeil appeals only the failureto-warn claims.

III.

Summary judgment is proper “if the pleadings, depositions, answers to interrogatories,

and admissions on file, together with the affidavits, if any, show that there is no genuine issue 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 verdict 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 inferencesfrom 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 unreasonably or inherently dangerous, a warning is required.” Gravis v. Parke-Davis & Co., 502

S.W.2d 863, 870 (Tex. Civ. App.SSCorpus

Christi 1973, writ ref’d n.r.e.) (citing RESTATEMENT (SECOND) OF TORTS § 402A

(1965)). 

Texaslawgenerallyholdsthat 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 specifically 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 reliance on Rolen to find adequacy as a matter of

law is inapposite. We agree. Although Reglan’s label mentions the conditions of which

McNeil complains, McNeil’s claim, unlike the

2

In Alm the court also cited with approval decisions from Texas appellate courts that have

adopted and applied the learned intermediary doctrine in casesinvolving a drug manufacturer’s duty

to warn about the potential hazards of prescription

drugs.
4

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 adequacy 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 follow, because, as the district court recognized,

even in the context of a learned intermediary,

“‘if the warning to the intermediary is inadequate 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 decidesto label a risk

as “comparatively rare” and also to provide a

numerical quantification of that risk, that number must be within a certain degree of accuracy.4

V.

The issue therefore is whether there is a

genuine issue ofmaterialfact asto whether the

label was misleading. This must be viewed in

terms of significant differences between the

disclosed risk and the actualrisk 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 professional 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 longterm use. Plaintiff’s expert, Dr. Thompson,

testified that by 1988 Wyeth had its “own market 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 Re3 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 differences in risk would send the adequacy question to

the jury, but when the differences in risk are signifi-

(continued...)

4

(...continued)

cant, their potentialmisleading 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 company’s warning with [that suggested in] the article,

a jury could infer that Parke, Davis’ version was

unreasonably diluted”).
5

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 metoclopramide 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 questioned in light of the availability of safer,

more effective drugs such as histamine-receptor blocking agents cimetidine

and ranitidine, and omeprazole. The

long-term efficacy and symptomatic benefit of metoclopramide have not been

documented.

Because the widespread long-term use of

Reglan suggeststhat Wyeth’sindication for use

for no more than twelve weeks was widely disregarded, a jury could infer that Wyeth’s warning wasineffective and thusinadequate. Therefore, 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 judgment incertaincircumstances. The “Contraindications” regulation requires that ‘[u]nder this

section heading, the labeling shall describe

those situationsin 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 contraindicated (absent compelling circumstances). Wyeth’s former medical monitor for Reglan also

testified similarly by agreeing that “Reglan

should not be prescribed for long-termtherapy

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 ofReglan suggeststhat Wyeth’sindication

for use for not more than twelve weeks was

widely disregarded, a jury could infer that the

warning was ineffective and therefore inadequate. It follows that Wyeth had a duty, under

Texas law, adequately to warn the learned intermediary 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 studies 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 concluded 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-controlstudy 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. 
6

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-termuse was

not just higher, but that it was “significantly”

higher, and that the labelwasthereforemisleading and inadequate.

Wyeth argues, however, that it was not required to update its label, because the studies

indicating that the risk for long-term use could

be a hundred times higher showed mere association with a disease, not necessarily causation.

Thus, Wyeth argues, because there could be a

variety of other factors responsible for the “association” found in these studies, that association does not necessarily require a warning to

physicians. This argument, however, is contradicted by the FDA regulations that require that

the labeling “be revised to include a warning as

soon asthere isreasonable evidence of an association of a serious hazard with a drug; a causalrelationship 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 federal law to warn physicians of a significant “association” betweentardive dyskinezia and longterm use of Reglan, that Texas law requiresthe

same thing. Texas law, however, does not absolve a manufacturer, as a matter of law, of a

duty to warn on grounds that no existing studies 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

renalfailure in patientsreceiving 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 renalfailure.” 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 labels and warn physicians of side effects based

on simple case reports, not on actual studies

showing causation. For example, a pharmaceutical company for which she was working

at the time (Eli Lily) inserted a warning that a

certain use of the drug Papaverine is contraindicated based only on a few case reports of its

apparentlycausing heart attacks, and no epidemiological or otherstudiesshowing causation.

She explained that the contraindicationattracted 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 counter 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 companies to do precisely what Wyeth claims it cannot do: tell physiciansthat a certain use is contraindicated evenifno clinicalor epidemiological studies exist that confirm causation or

degree ofrisk. Certainly, it is easier for a manufacturer to make an off-label use contraindicated when that use provides only a minimal

amount of sales from that drug as opposed to

when the off-label use providesthe majority of
7

its sales, as allegedly it is with Wyeth and Reglan. But it is precisely this factSSthat off-label

use allegedly provided a majority of Wyeth’s

salesSSthat would create Wyeth’s duty to physicians not to be misleading about the risk of

long-term use.

Admittedly, the physician, in the exercise of

professional judgment, can disregard the warnings or contraindications provided bythe manufacturer. But then he does so at his own risk,

and most physicians are likely reluctant to do so

absent more concrete evidence about the benefits of long-term use, evidence that is absent in

this case. Even Dr. Wilkinson, who initially indicated that he would not have changed his

long-term prescription of Reglan even if he had

read the studies now cited byMcNeil, acknowledged 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 (ifstill 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 asto whether pharmacologicalevidence should have alerted Wyeth about the

significantly increased risk from long-term use.

Under Texas law, causation is generally an issue 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 causalrelationship between the condition 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 metoclopramide orschizophreniamedications(Haldol and Thorazine) isto diminish the effects of

dopamine in the brain. The inability of dopamine to produce its effects causesEPS (including 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 testified that these side-effectsfor 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 ofside effectsthat

we associate with dopamine blockers. And

in thissense, it’s really no different that any

so-called neuroleptics, the drugs that produce the calming effect in schizophrenia.

So it’s just like Thorazine or Haldol or any

of the other antipsychotics. It’s highly predictable 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 further 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
8

“dopamine antagonists” such as phenothiazines

(which include Thorazine), Reglan “may produce 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 inMetoclopramide long termand

Thorazine long-term. So [the label] wouldn’t be correct in terms of being comparatively rare . . . . 25 percent isn’t rare compared to anything.

Therefore, we cannot say as a matter of law

that Reglan’slabelwas adequate even ifit 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 “producing 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, because there is a genuine issue of materialfact as

to whether the label’s inadequacy caused McNeil’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 ofthe significant risk of

tardive dyskinesia associated with long-term

Reglan use and that such information certainly

would have changed the “risk/benefit” analysis” 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 testimony 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 discussing 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 plaintiff would have rejected the drug if informed,

the inadequate labeling could be a “producing”

cause ofthe injury, because it effectively sabo-
9

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 question should go to the jury. The summary judgment is REVERSED, and this matter is REMANDED 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 intermediary,” id., this reliance seems less reasonable where

the learned intermediary fails to pass necessary information to the patient because the manufacturer

has understated the degree of risk.