Extra Strength Tylenol, one of the most aggressively-marketed consumer products in the country, has been making news again lately. The media focus has been on how researchers built on previous findings that “acetaminophen reduced neural responses to social rejection in brain regions previously associated with distress caused by social pain” and found that Tylenol can reduce existential unease and cause people to be less morally judgmental. It is an undeniably powerful drug.
But the bigger news from a patient safety standpoint has been the creation of “multidistrict litigation” against McNeil Pharmaceuticals. The order means that the bulk of Tylenol injury lawsuits while be handed, at least for pretrial purposes, here in the federal court in Philadelphia, a couple blocks from our office. A year and a half ago, I wrote a post about how courts were lagging behind the science on acetaminophen, and it seems that the tide is changing on that.
The risk of acute liver failure when using Tylenol certainly isn’t new, and even Tylenol lawsuits aren’t new. As just one example, more than twenty years ago Antonio Benedi, a regular wine-drinker (but by no means an alcoholic) “had been taking Extra-Strength Tylenol in normal, over-the-counter doses since February 5, 1993 for flu-like aches,” when, five days later, he “was admitted to the hospital on February 10, 1993 in a coma and near death due to liver and kidney failure.” Benedi v. McNeil-PPC, Inc., 66 F.3d 1378 (4th. Cir. 1995).
The hospital’s pathologist examined Benedi’s damaged liver and concluded that the injury was characteristic of acetaminophen toxicity. In the lawsuit that followed, Benedi’s lawyers proved that even “therapeutic” doses of Tylenol – i.e., doses within the limits given on the label – could cause acetaminophen hepatotoxicity and acute liver failure when combined with ordinary amounts of alcohol. The Tylenol warning label was subsequently updated to warn about alcohol use while taking acetaminophen.
Since then, not much has changed even while acetaminophen liver injuries continue to mount. Researchers know “acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States,” and that the incidence of Tylenol-induced acute liver failure is on the rise. Some estimates by the American Association of Poison Control Centers suggest more than 50,000 emergency department visits every year related to acetaminophen.
There were two inadequate changes over the past decade. In 2005, the over-the-counter Tylenol label was modestly updated to warn that “severe liver damage may occur if more than 4,000mg of acetaminophen is taken.” In 2011, Tylenol changed the label on its Extra Strength Tylenol formulation (the 500mg pills) to impose a maximum of 6 caplets every 24 hours, or 3 grams a day.
Neither of these changes really get to two biggest problems: many routine medical conditions increase Tylenol toxicity and Tylenol has no safety margin for its use.
Starting with the first problem, McNeil Laboratories and Johnson & Johnson are simply wrong that a patient has to take more than 4 g of Tylenol to run the risk of acute liver failure or death. Way back in 1987, researchers confirmed the metabolic process by which, when mice weren’t fed as much, their livers didn’t produce as much glutathione, and the liver had much greater difficulty clearing acetaminophen. It’s easy to see that and think, well, how often do people really “fast” – as in, go without any food at all – and take a significant amount of Tylenol?
But “fasting” in this context doesn’t mean abstaining from food entirely, and, more to the point, think about when people consistently take the maximum dose of Tylenol – for example, when they are sick with a cold or the flu, or when they are recovering from surgery, times when people don’t tend to eat much. Last time you had the flu, even if you could keep food down, you weren’t hungry, so you didn’t eat much, but your fever kept going up and you felt aches and pains throughout your body, and so you took Tylenol as often as the label said you could. They even market it for this purpose, like “Tylenol Cold & Flu Severe.”
Bad idea. That’s where the “increased hepatotoxicity” comes in. In just a few days, you can go from “having a flu” to “in the hospital with ‘Acetaminophen related hepatotoxicity,” to the liver transplant list – or worse. It’s scary, and it happens to consumers all the time. Indeed, the problem might be even worse than we think: as researchers noted two years ago, “the cause of liver injury in 14% of patients with acute liver failure remains unknown.” Their data lead them to conclude there was a “high prevalence of unrecognized or uncertain acetaminophen toxicity among subjects with indeterminate acute liver failure.”
If you have any other condition that affects the liver, or if you’re anything other than a perfectly healthy adult, then the risks are even worse. Consider this 2001 article from the American Academy of Pediatrics, which lists “Conditions and Situations That May Increase the Risk of Acetaminophen Toxicity” including Diabetes mellitus, Obesity, Chronic undernutrition, Prolonged fasting, Family history of hepatotoxic reaction, and Concomitant viral infection.
Moving to the second problem, there’s no denying that, even in perfectly healthy patients, at some dosage Tylenol is likely cause acute liver failure. The question are: what is that level, and how often do people cross it? Many studies have found, for example, “that there is a narrow therapeutic margin and that consistent use of as little as 7.5 g/day may be hazardous.” The phrase, “narrow therapeutic margin,” is a euphemism for “the recommended dose brings you awfully close to permanent injury and potentially death.” Other studies have found the number could be much lower, so that consumers who frequently take just a little bit more Tylenol than recommended – the so-called “staggered overdose” – are at far greater danger of liver injuries, and some slight tipping point like a flu or some alcohol use can push them over the edge.
We’re all familiar with cases of people attempting suicide by overdosing on Tylenol, but that’s not the whole story: there are literally hundreds of published medical studies describing unintentional overdoses on Tylenol, typically referred to as “therapeutic misadventures.” How does this happen? I have one guess: patients don’t know just how dangerous acetaminophen can be. Although that warning references “liver damage,” it doesn’t convey the two most serious potential side effects: acute liver failure and death. As the Washington Post noted in a long article earlier this week about Medicare, one of the biggest contributors to health problems today is “non-compliance” with medications. The consequences of just a few days of “non-compliance” or a “therapeutic misadventure” with Tylenol, however, are far worse than with any other over-the-counter pill – but consumers don’t know that.
Put simply, there are no other over-the-counter drugs with such a narrow window that, if you merely take an extra four or five pills, you could die, and yet Tylenol is labeled and advertised not just as being like everything else, but as being safer than other drugs.
As noted above, Tylenol litigation isn’t new, but the creation of the multi-district litigation (“MDL,” which is different from a class action) really changes things. Over 50,000 people go to the emergency room with these injuries every year, but Johnson & Johnson and McNeil aren’t going to do anything. They sell over $1 billion a year of Tylenol. (Read more about their branding initiatives over the past fifty years here). The FDA isn’t going to do anything, either.
These days, there’s only one way unsafe drugs are ever pulled from the market or given better warnings: when the company is held accountable to its victims, it makes less of a profit, and so moves on to something else. The creation of the multidistrict litigation is important because it will help gather together these hundreds, potentially thousands, of cases, allowing them to have strength in numbers, and preventing the company from spending literally millions of dollars fighting each one of them to try and dissuade other plaintiffs and their lawyers from bringing individual lawsuits.
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