The Big Bucks in Tylenol
The Long War on Aspirin
By FRED GARDNER
J ohnson & Johnsonís Acetaminophen is the active ingredient in Tylenol. McNeil Laboratories first marketed it (in combination with a barbiturate) in 1953 as a safer alternative to aspirin. The big selling point was that aspirin, then the best-selling painkiller, is hard on the stomach. Preceding the launch, McNeil had hired a leading critic of aspirin, a gastroenterologist named James Roth, and organized a conference. "In 1951," the company history recounts, "the safety and efficacy of acetaminophen was described at a scientific symposium in New York City sponsored by the Institute for the Study of Analgesic and Sedative Drugs.
According to the research reported at this symposium, acetaminophen was found to be as effective as aspirin for pain relief and fever reduction, but without the side effects of aspirin such as stomach irritation, gastrointestinal bleeding, and impairment of the blood to clot normally."McNeil launched Tylenol Elixir for Children -pure acetaminophen- in 1955. The company history says, "The outstanding success of Tylenol was attributed to a unique marketing strategy: to inform health care professionals of the undesirable effects of aspirin and ask them to recommend Tylenol to patients susceptible to these effects." After Johnson & Johnson acquired McNeil in 1959 the safer-than-aspirin pitch was complemented by a massive giveaway of the product to doctors and hospitals, creating market share by irresistible financial force.
In the 1970s J&J sales reps began solemnly informing healthcare professionals that aspirin had been associated with "Reye's syndrome" (pronounced "Rise") a potentially fatal condition involving the liver and ultimately the brain of infants and children following viral illness. In 1982 the Surgeon General issued a warning to this effect. (Ralph Nader's Public Health Research Group received credit in the media for pressuring the government to act.) In 1986 the FDA required all aspirin products in the U.S. to carry a warning label stating "children and teenagers who have or are recovering from chicken pox, flu symptoms or flu should NOT use this product."
A second sentence was added in 2003: "If nausea, vomiting, or fever occur, consult a doctor because these symptoms could be an early sign of Reye's Syndrome, a rare but serious illness."
It is a tribute to Johnson & Johnson's marketing effort that so many people have heard of Reye's and its association with aspirin, given how extremely rare it is. In '86 there were approximately 100 cases in the U.S. In the UK there were 172 cases reported between 1986 and 1999 -only 17 associated with aspirin use. Aspirin (an extract of willow bark) is not as benign as cannabis, but it, too, has been on the receiving end of a corporate disinformation campaign. J&J has whipped up exaggerated fears of lethality.
In 2004 an Australian government committee evaluated the Reye's warning statement on aspirin in a report that noted numerous inconsistencies in the diagnosis itself. "The viral illness which proceeds Reye's Syndrome varies" from country to country, the report said. In the US almost all Reye's cases involve varicella or influenza A or B; but in the UK and Australia, gastrointestinal and other viruses are involved. "In the US, the cases are usually over five years of age, with a median age of six-seven years. In the UK the median age of cases was 10-15 months ... These differences between Reye's Syndrome as it is commonly seen in the US and the UK and Australian cases, have led to questions about whether the term 'Reye's Syndrome'refers to the same disease in both countries or, in fact, whether it refers to a single disease at all, or a heterogeneous group of disorders ...
"Despite over 20 years of study, there is still debate about the nature of the association between aspirin and Reye's Syndrome," according to the Australian report, whose authors reviewed all the relevant studies. In many cases it turned out that the symptoms attributed to Reye's were actually manifestations of inborn errors of metabolism -the body couldn't make enough of a certain enzyme. In 1987 a researcher named Orlowski at the Children Hospital in Camperdown -Reye's old hospital- reviewed the records of 20 patients diagnosed with Reyes and found that only one had been administered aspirin, and "this patient had a zero salicylate level when admitted hospital after severe vomiting."
In 1999 Orlowski reevaluated 26 surviving Reye's Syndrome patients who had been assessed in 1990 and found that 18 had been diagnosed in the intervening years with other conditions, 15 of them with inborn metabolic disorders. Orlowski also reanalyzed the records of all 49 patients in the 1990 study and determined that "six had probable Reye's Syndrome, two had possible Reye's syndrome, 23 were unlikely to have had Reye's Syndrome, and Reye's Syndrome was excluded in 18 patients."
The report notes that "A number of studies have been conducted to investigate how aspirin could be involved in Reye's Syndrome. However, no clear mechanism of action has been defined. It is clear from the epidemiology studies that other factors apart from viral illness and aspirin exposure are involved ... The data available does not confirm a specific or causal role for aspirin. It is likely that, if aspirin is involved in Reye's syndrome, it acts to compound injuries to an already stressed metabolism."
More Americans probably fear aspirin as a cause of Reye's syndrome than fear acetaminophen as a cause of severe liver damage. Yet, as discussed in a previous column there are approximately 2,000 cases of acute liver failure annually in this country, resulting in about 500 deaths. Acetaminophen overdose is the leading cause for calls to Poison Control Centers (133,000 in '04, more than half required a trip to the ER or doctor's office). The mechanism of action is not mysterious: the liver, as it breaks down acetaminophen, makes a toxic compound, N-acetyl-para-benzoquinoneimine, which is then transformed to a benign one. In cases of overdose, the liver can't fully process the toxin, which accumulates. For those with liver damage from hepatitis and/or heavy alcohol use, a "therapeutic" dose can lead to acute failure. Recently Dr. William Lee presented data at a conference showing that one in eight cases of acute liver failure attributed to hepatitis B also involves acetaminophen poisoning.
Your correspondent asked Dr. Lee why manufacturers combine -"bundle"- acetaminophen with synthetic opiates, as in Percocet and Vicodin. (Tylenol with codeine is ubiquitous, while most U.S. pharmacies don't even stock aspirin with codeine.) Lee replied, "The point of the bundling from the physician's standpoint is that you do not need a triplicate form to fill in which most of us use very rarely -have, but keep in a bottom drawer and (like me yesterday) cannot find... when we are on the run and trying to get someone relief.
These compounds are the only ones that can be called in and written on a plain scrip. Not sure how it got enacted, however." If the rationale for making the acetaminophen-opioid drugs available by "plain scrip" is regulatory rather than medical, we suspect that J&J lobbyists had a hand in establishing it. This is not a conspiracy theory, it's a conspiracy hypothesis. There are people in DC who should be able to substantiate or disprove it. The question is: which lobbyists working for which corporations fixed which codes so that "bundling" drugs would facilitate prescription writing?
Johnson & Johnson has paid out countless millions of dollars over the years to settle suits by Tylenol victims and minimize adverse publicity. Occasionally the wall of silence by the corporate media gets breached, but the message that Tylenol causes liver damage has yet to reach the masses. A 1998 article in Forbes by Thomas Easton and Stephen Herrera critiqued J&J's strategy: "J&J has made grudging concessions, strengthening the warning label a little at a time... Why not warn about people about possible liver failure? J&J says that 'organ specific' warnings would confuse people. Why not talk about the risk of death? That would promote suicides, says the company." The Forbes piece concluded, "[CEO James] Burke's successor has a painful choice. He can rewrite the label, putting on it the verbal equivalent of a skull and crossbones. Or he can go on paying off victims, and hope for the best." Richard Cowan posted the Forbes piece on Marijuananews.com, with a commentary contrasting the safety profiles of Tylenol and cannabis. That was about 2,500 deaths ago.