One of the more sobering parts of being a trial lawyer is reviewing intakes of potential cases. We routinely talk with people who have just lost a spouse or child or who have recently suffered an injury that will leave them permanently disabled. Many of these accidents happened in the course of activities we all know to have an element of danger, but many involve doing the same thing a million other people do every day. No one expects that giving their kid Motrin will cause a horrific skin disease or that their tap water might be so polluted that it’s flammable.
Now, a growing body of medical studies shows that acetaminophen (Tylenol in the US, Paracetamol everywhere else) is dangerous at far lower doses than previously believed. It’s been known for decades that acetaminophen overdoses cause liver damage (for example, “acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States,” and some estimates by the American Association of Poison Control Centers suggest more than 50,000 emergency department visits every year related to acetaminophen), particularly when combined with alcohol, but it was generally considered safe if taken at anywhere near the recommended amounts.
Recent studies suggest that’s not the whole story. Just a few weeks ago, a new study in the British Journal of Clinical Pharmacology found that “staggered overdoses,” in which patients repeatedly took amounts slightly higher than the recommended dosage, were the cause of a substantial portion of the hospital admissions for acetaminophen-induced liver damage, and could be more dangerous than individual overdoses, in part because staggered overdoses were harder to diagnose and treat.
In June 2009, the FDA’s Drug Safety and Risk Management Advisory Committee, Nonprescription Drugs Advisory Committee, and the Anesthetic and Life Support Drugs Advisory Committee all voted in favor of:
- Reducing the current dosage strengths of acetaminophen in nonprescription products to below 4 grams/day
- Limit formulations of over-the-counter liquid doses of acetaminophen
- Eliminating prescription acetaminophen combination products (e.g., oxycodone)
- Requiring a boxed warning for prescription acetaminophen combination product
The FDA disappointingly didn’t act on most of that, and instead took eighteen months to take the weakest action it could:
On January 13, 2011, FDA announced that it is asking manufacturers of prescription acetaminophen combination products to limit the maximum amount of acetaminophen in these products to 325 mg per tablet, capsule, or other dosage unit. FDA believes that limiting the amount of acetaminophen per tablet, capsule, or other dosage unit in prescription products will reduce the risk of severe liver injury from acetaminophen overdosing, an adverse event that can lead to liver failure, liver transplant, and death.
The size of the individual dosage unit was never the problem, though. As the Acetaminophen Hepatotoxicity Working Group for the FDA Advisory Panel found in its report, the problem was far more complicated than the pills being too big:
There is no single factor that leads consumers (also referred to as patients in this report) to develop acetaminophen-related liver injury. The contributing conditions for these cases are multi-factorial and require different interventions that attempt to address each factor. For example, when someone takes an amount greater than labeled, it is unclear whether it is a case of failing to read the directions, failing to understand the directions, failing to understand that severe liver injury can result from not following the directions or failing to realize that more than one of the medications used contained acetaminophen.
The Working Group concluded, “Thus, it is necessary to address all of these causes in attempting to prevent future cases, making clear directions conspicuous and easy to understand and making consequences of overdose unequivocally clear.” (Emphasis added.)
It’s not just the pill size. It’s not just the recommended maximum dosage. The core problem is that consumers and patients have learned, from years of Tylenol advertising and liberal use of acetaminophen by their parents, nurses, and doctors, that it’s a “safe” drug, like caffeine, that can be used every day and without much consequence unless you have a particular susceptibility to it or if you intentionally take way too much. Consumers look at recommended dosages like they do speed limits: you can use that amount without any problems, but try not to go too far above it. Problem is, if you did that with the 4 grams/day of acetaminophen guideline, you had a much higher risk of liver damage, even if you didn’t do it all the time.
Thankfully, McNeil Consumer Healthcare, maker of Tylenol, got the message — at least part of the message — and in July voluntarily altered its warning labels for Tylenol Extra Strength with new recommended dosages:
- Take 2 caplets (1,000 mg) every 6 hours while symptoms last (revised from 2 caplets every 4 to 6 hours).
- Not to take more than 6 caplets (3,000 mg) in 24 hours, unless directed by a doctor (revised from 8 caplets in 24 hours).
All of which is to say, everyone agrees, explicitly or implicitly, that acetaminophen can be dangerous even at 4 grams / day.
It doesn’t take much of a logical leap to see why, even without a study confirming that specific conclusion. It’s already established that “acetaminophen hepatotoxicity can also occur even with therapeutic doses in certain conditions” like alcohol, malnourishment, and combined use with other drugs and that “even at lower-than-therapeutic doses, induction of CYP450 enzymes by drugs or chronic alcohol consumption may lead to an increase in the formation of NAPQI, increasing the risk of hepatotoxicity.”
But as I’ve discussed before (in, for example, the context of vinyl chloride), having a strong, sensible, evidence-based argument isn’t always enough to make it to a jury. Courts routinely dismiss cases despite ample scientific support behind their claims. Just ask Margalit Ratner.
Margalit Ratner, like many people (myself included, until I learned more through my legal practice), “ingested Tylenol and Extra Strength Tylenol as needed in order to relieve migraine headaches” for more than a decade, and then:
The plaintiff asserts that her usage never exceeded the maximum recommended dosage. … In 2001 a magnetic resonance imaging exam indicated that the plaintiff had “micronodular cirrhosis.” In July 2004 the plaintiff underwent liver transplant surgery. Thereafter, the plaintiff was diagnosed with “incomplete septal cirrhosis” (hereinafter ISC), a condition that reflected either an ongoing injury or a regression of liver scarring. In addition, the plaintiff was diagnosed with “hepatoportal sclerosis” (hereinafter HPS), a relatively uncommon liver condition which can lead to the shrinking of the liver and the development of “portal hypertension.”
Margalit sued McNeil in New York state court for “damages for negligence, failure to warn, defective design, breach of implied and express warranties” and violation of New York consumer laws.
The lawsuit, however, was dismissed on summary judgment before a jury heard a word. Last month, the intermediate appellate court in New York affirmed the dismissal.
Ratner had a serious injury — liver failure, liver transport, and continuing liver problems — which was apparently caused by someone else’s negligence: McNeil failing to warn patients about the real level at which consistent Tylenol use was dangerous. It should have been a clear-cut case for the jury to decide. For trial, Ratner’s lawyers called all the right experts.
- a gastroenterologist and a hepatologist, [who] was prepared to testify that the toxic effects of acetaminophen could be seen at doses that were “only slightly greater than recommended therapeutic doses,” and that people who are fasting, malnourished, or “predispos[ed]” are at a greater risk of acetaminophen toxicity, even at therapeutic doses.
- a pathologist and professor of hepatopathology, planned to testify about how exposure to hepatotoxins can result in toxic hepatitis, which can then lead to the development of hepatic fibrosis and liver cirrhosis.
- a pharmacologist, [who] would testify that the defendant failed to provide an adequate warning to consumers about the hepatotoxicity of acetaminophen, and that had methionine or other compounds been added as an ingredient to Tylenol, the hepatotoxicity of acetaminophen would have been effectively eliminated.
- a former chief medical officer with the Food and Drug Administration, [who] would testify that the defendant had downplayed the potential risks posed by the hepatotoxicity of Tylenol, and failed to design, test, label, and market Extra Strength Tylenol to consumers in a reasonably prudent and safe manner.
(All descriptions taking from the appellate court’s own description.)
That wasn’t enough for the trial court of the appellate court to let the case go to a jury, though. New York is, like Pennsylvania and New Jersey, a Frye state (as in, Frye v United States, 293 F 1013) that permits “expert testimony based on scientific principles, procedures, or theories only after the principles, procedures, or theories have gained general acceptance in the relevant scientific field.” The courts held that the gastroenterologist / hepatologist, pathologist / professor of hepatopathology, pharmacologist, and former chief medical officer with the FDA were all going off the rails because they couldn’t point to a specific study showing exactly what happened to Ratner. Sure, they pointed to dozens of studies supporting what they said, and their own clinical practice and theories, but that wasn’t enough.
As I’m sure you can tell from the above, I think the court’s conclusions were flat-out wrong on the law and on the science. The “principles, procedures, or theories” by which acetaminophen use of any amount causes liver damage have more than just “general acceptance” in medicine — they’re the only game in town. Check MedScape. If a doctor or medical researcher at McNeil or the FDA said they truly didn’t believe that regular use of Tylenol could cause liver damage, they would be fired and laughed out of the place.
As the 16th-century physician and alchemist Paracelsus said, “For everything is a poison, and nothing is without poison. Only the dose permits a thing not to be poisonous.” In the right dose, water is toxic. There’s no question that Tylenol is toxic; all of the “generally accepted principles, procedures and theories” of science and medicine agree. The only question is at what dose acetaminophen begins to cause serious side effects, and those specific factual questions relating to each individual injured consumer are rightly left for the jury, not for judges. That’s the law, and it comports with the science. It’s a shame to see the New York courts get it so wrong.
The sad irony here is that, like with many other drug recall and class action lawsuits (Vioxx in particular comes to mind), in time new studies will be performed that will most likely show exactly what Ratner was alleging, i.e. that prolonged use of the previously “recommended” doses of acetaminophen can nonetheless cause liver damage. Until then, plaintiffs just have to cross their fingers and hope for less unfavorable panel of judges. Tort reformers like to throw around the term “junk science” as a smear against trial lawyers, but, truth is, courts are even more likely to junk good science to let powerful corporations avoid responsibility.