Terry v. McNeil-PPC, Inc. (In re Tylenol (Acetaminophen) Mktg., Sales Practices & Prods. Liab. Litig.)

• Decision Date: 13 November 2015
• Docket Number: MDL NO. 2436,Civil Action No. 2:12-cv-07263,2:13-md-02436
• Citation: 144 F.Supp.3d 699
• Court: U.S. District Court — Eastern District of Pennsylvania
• Parties: In re: Tylenol (Acetaminophen) Marketing, Sales Practices and Products Liability Litigation This Document Relates to: Rana Terry, as Personal Representative and Administrator of the Estate of Denice Hayes, Deceased, Plaintiff, v. McNEIL-PPC, Inc., McNeil Consumer Healthcare, and Johnson & Johnson, Inc., Defendants.

144 F.Supp.3d 699

In re: Tylenol (Acetaminophen) Marketing, Sales Practices and Products Liability Litigation

This Document Relates to:

Rana Terry, as Personal Representative and Administrator of the Estate of Denice Hayes, Deceased, Plaintiff,
v.
McNEIL-PPC, Inc., McNeil Consumer Healthcare, and Johnson & Johnson, Inc., Defendants.

MDL NO. 2436
2:13-md-02436
Civil Action No. 2:12-cv-07263

United States District Court, E.D. Pennsylvania.

Signed November 13, 2015

144 F.Supp.3d 703

MEMORANDUM

Stengel, District Judge

This case is part of a Multidistrict Litigation (MDL) involving claims of liver damage from the use of Tylenol at or just above the recommended dosage.¹ This is the first “bellwether” scheduled for trial.² The plaintiff claims that her sister died of acute liver failure after taking Extra Strength Tylenol “as directed” by its label.³ She asserts that defendants Johnson & Johnson and McNeil—the makers of Tylenol—knew or should have known that consumers may develop acute liver failure after taking Extra Strength Tylenol at or just above the recommended dose, yet failed to warn users of this risk.

The defendants moved for summary judgment on the plaintiff's failure-to-warn claim, arguing that the plaintiff has not offered sufficient evidence of this claim and/or the claim is preempted by federal law. For the reasons explained below, I will deny the defendants' motion.

144 F.Supp.3d 704

I. A HISTORICAL OVERVIEW OF TYLENOL⁴

The plaintiff's claims are different from those previously asserted against the defendants about the safety of Tylenol. While previous cases have questioned whether Tylenol can cause liver damage, this case and others in this MDL question the extent of such damage and the quickness with which it can occur. A historical overview of the regulation and science of Tylenol is helpful in explaining the plaintiff's claims.

a. TYLENOL, ACETAMINOPHEN, AND LIVER DAMAGE⁵

Extra Strength Tylenol is an over-the-counter (OTC) pain reliever; consumers do not need a prescription to buy it. The active ingredient in Extra Strength Tylenol is acetaminophen, which is an analgesic and antipyretic or pain reliever and fever reducer.⁶ Defendant McNeil manufactures and markets many different Tylenol products, including Extra Strength Tylenol and Regular Strength Tylenol. The two products differ in that one tablet of Extra Strength Tylenol contains 500 mg of acetaminophen while a tablet of Regular Strength Tylenol contains only 325 mg of acetaminophen per tablet. Johnson & Johnson is the parent company of McNeil and is involved in managing its operations.

Acetaminophen was first synthesized as a pain reliever in the 1890s and has been available OTC since the 1960s.⁷ Tylenol is one of more than 600 acetaminophen-containing products on the market in the United States in OTC and prescription formulations.⁸ Acetaminophen is one of the most widely used OTC drugs.⁹ Twenty percent of Americans—60 million people—ingest an acetaminophen-containing product each week.¹⁰ The Food and Drug Administration

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(FDA), which regulates OTC drugs, has found acetaminophen to be a “safe and effective OTC analgesic” when taken in recommended doses and used according to the label.¹¹ However, acetaminophen has been known to cause severe liver damage.¹²

i. Acetaminophen's Link to Acute Liver Failure

Acetaminophen is different from other OTC pain relievers in two ways: 1) it is the only one to have an antidote, and 2) its maximum total daily limit is the same for both OTC and prescription products.¹³ Acetaminophen is a “dose-related toxin,” meaning it can be safely used at certain doses but harmful at higher doses.¹⁴ As a result, there is evidence that it has a “narrow therapeutic margin”—i.e., there is little difference between the current maximum recommended dose of acetaminophen and the doses that could cause liver injury.¹⁵ The parties debate how narrow this margin is.

A simplistic explanation of how the body metabolizes acetaminophen helps frame the issues in this case. Typically, glutathione—an antioxidant found in the liver—will bind to the toxic parts of acetaminophen, to neutralize them and prevent them from harming the body.¹⁶ These neutralized toxins are then excreted.¹⁷ However, if the body does not have enough glutathione, those toxins can build up in the liver, causing acute liver failure (ALF). Glutathione stores may be low when a person is malnourished or when the liver has been neutralizing a lot of toxins at once.¹⁸

144 F.Supp.3d 706

“Acute liver failure (ALF) is a rapid deterioration of the organ's ability to function.”¹⁹ Patients who experience ALF can fall into a coma or die.²⁰ They may require a liver transplant.²¹ A person who has recovered from ALF may still be at risk of redeveloping it, if the person again consumes too much acetaminophen.²²

If acetaminophen-induced ALF is recognized quickly, acetaminophen's antidote (N -acetylcysteine or NAC) can be given to a patient to supply glutathione and prevent or decrease liver injury.²³ However, persons who have developed ALF from an unintentional acetaminophen overdose may not realize their liver injury because symptoms of ALF are not readily apparent or may look like the symptoms the acetaminophen is being used to treat (i.e., flu symptoms).²⁴

ii. FDA Actions to Address Acetaminophen-Induced Acute Liver Failure

The majority of acute liver failure cases in the United States are related to the use of acetaminophen.²⁵ Each year, acetaminophen is responsible for hundreds of deaths and liver transplants, in addition to tens of thousands of hospitalizations.²⁶ These acetaminophen-induced liver injury patients include both people who are intentionally trying to harm themselves (i.e., attempting suicide) and those who take acetaminophen for therapeutic reasons (i.e., to treat physical pain).²⁷ There is evidence that patients

144 F.Supp.3d 707

taking acetaminophen at 4 g per day—the recommended maximum daily dose until recently—may be at risk of developing acute liver failure.²⁸

Medical literature began questioning the safety of acetaminophen at or just above therapeutic levels as far back as the 1980s.²⁹ During the 1990s, members of the medical community continued to raise concerns about acute liver failure occurring in patients at or even lower than the maximum daily dose of 4 grams.³⁰ Throughout this same time period, McNeil was also actively engaged in research and development of a drug or combination of ingredients that would reduce or eliminate acetaminophen's potentially toxic effects on the liver.³¹

In 2002, the FDA convened an Advisory Committee to discuss ways to prevent liver injury caused by unintentional acetaminophen overdose.³² During the Committee Meeting, the FDA presented findings from medical literature: 1) that hepatotoxicity may occur “at recommended doses of APAP,” 2) that such cases were linked to risk factors such as alcohol use and/or fasting, and 3) that some cases of unintentional overdose led to death.³³ The FDA also presented its own findings from a review of its own internal Adverse Event Reporting (AER) database. The FDA found hepatotoxicity (i.e., liver damage) in persons who have ingested less than 4 grams/day and who had risk factors like alcohol and “poor nutritional status.”³⁴ As a result, the American Association of the Study of Liver Disease (AASLD) and the FDA offered specific recommendations for enhancing safety warnings and instructions for acetaminophen-based products.³⁵

In 2006, the FDA proposed a rule to strengthen warnings regarding the risk of liver damage from taking acetaminophen.

144 F.Supp.3d 708

After receiving and reviewing public comments, the FDA promulgated a final rule outlining the liver warnings it found to be necessary.³⁶ This final rule, issued in 2009, is explained further below.

In February 2008, the Acetaminophen Hepatotoxicity Working Group for the Center for Drug Evaluation and Research of the FDA met to discuss ways to address unintentional acetaminophen overdose.³⁷ The Group outlined several recommendations, including a reduction in the maximum tablet strength from 500 mg to 325 mg.³⁸ The reduction in tablet strength was intended to reduce the overall recommended daily dose of Tylenol from 4,000 mg to 3,250 mg.³⁹ This recommendation was made over the objection of an unnamed acetaminophen manufacturer which asserted the data did not support a need for the change; the Group looked at Adverse Events Reports (AERs) showing that daily doses of 4 g presented a risk for some individuals.⁴⁰ Survey data also showed that “people routinely and knowingly take more than the recommended dose of OTC pain relievers.”⁴¹

In June 2009, a joint meeting of several FDA Advisory Committees was held to discuss the issue of liver injury related to acetaminophen use.⁴² The joint committee recommended that the warning on acetaminophen products be further strengthened and the recommended dose reduced.⁴³

b. THE REGULATORY FRAMEWORK FOR TYLENOL

OTC drugs are approved by the FDA through two separate routes: the New Drug Application (NDA) process and the monograph system.⁴⁴ During the forty or

144 F.Supp.3d 709

so years Extra Strength Tylenol has been available OTC, it has been regulated under both FDA regulatory processes.

i. New Drug Application v. Monograph Process

The NDA process requires specific products be approved for sale with specific labeling.⁴⁵ The monograph system allows for the marketing of OTC drugs containing particular ingredients, which were already on the market before the FDA established the monograph system in 1972.⁴⁶ These active ingredients, which include acetaminophen, were ones which had been found to be generally safe and effective through general usage.⁴⁷ Therefore, they were allowed to remain on the market OTC.

Because Extra Strength Tylenol's active ingredient is acetaminophen, it was automatically regulated by the monograph system as of 1972. In 1975, the FDA approved Extra Strength Tylenol as “safe and...