Tylenol Safety Debated -- Again

Recommended Dose Safe, but Overdose Danger Debatable

Medically Reviewed by Brunilda Nazario, MD on July 23, 2004
From the WebMD Archives

July 23, 2004 -- Is acetaminophen -- best known as Tylenol -- safe enough for over-the-counter sales to continue?

Yes, most experts say. But every year, acetaminophen overdose is linked to 458 deaths from acute liver failure. Acetaminophen poisoning is implicated in half of all U.S. liver failures.

Yet tens of millions of Americans use Tylenol regularly. The FDA says the drug's benefits far outweigh its risks. Not so, argues liver disease expert William M. Lee, MD, professor of internal medicine at the University of Southwestern Medical Center in Dallas.

"It still must be asked: Is this amount of injury and death really acceptable for an over-the-counter pain reliever?" Lee writes in the July issue of Hepatology.

Unintentional Overdose

Lee warns that unintentional acetaminophen overdoses are often taken for several reasons:

  • People take several products, unaware that each one contains the maximum safe dose of acetaminophen.
  • People abusing narcotics often don't realize that the drug is paired with acetaminophen. As their tolerance for the narcotic increases, they take larger doses -- and get huge doses of acetaminophen.
  • People in pain take more and more pain reliever to get relief, far exceeding the recommended dose.
  • Chronic alcoholics are more sensitive to acetaminophen toxicity.

The largest recommended dose of acetaminophen comes in Tylenol Extra Strength products. The label instructs users to take two 500 mg pills -- a dose of 1 gram. The label warns people not to take more than 4 grams -- eight pills -- in a single 24 hour period.

Lee notes that most unintentional overdoses occur with 34 grams, taken, on average, over the course of three days.

That's a lot of pills, says Frank A. Anania, MD, director of hepatology at Emory University School of Medicine in Atlanta.

"Yes, this drug can be dangerous if people take 8 to 10 grams in a day. But that is 16 extra-strength tablets," Anania tells WebMD. "But even if you take eight pills every day for three days, that's only 12 grams. So that is a lot of Tylenol in these 'unintentional overdoses.' This brings up the question of whether the safety issue is one that can truly be addressed by more regulation of this drug."

Acetaminophen Misconceptions Abound

Lee's article is one of two point/counterpoint editorials in Hepatology. The companion piece is by Barry H. Rumack, emeritus director of the Rocky Mountain Poison and Drug Center and professor of pediatrics at the University of Colorado School of Medicine.

Rumack says Lee is working backward, trying to find out why people are dying of liver failure. Sure, he's finding evidence that sick people take Tylenol, but that's what sick people tend to do. Studies that look at what happens when people take acetaminophen, he says, don't raise red flags.

"I do not believe acetaminophen, at therapeutic doses, taken according to directions, produces toxicity," Rumack tells WebMD. "The few reports that suggest that don't prove anything, because the blood levels they are based on don't satisfy any scientific basis. All prospective studies show absolutely no toxicity."

One common misconception about acetaminophen, Lee says, is that it shouldn't be used by people who drink alcohol.

"I just don't believe that the casual alcohol drinker is at risk at therapeutic doses," Rumack says. "There is no data that acetaminophen is dangerous for a hangover."

Rumack argues that the dose of acetaminophen needed for liver toxicity is nearly 16 grams -- 32 extra-strength acetaminophen tablets. In chronic alcohol users, the toxic dose is lower -- 13 grams, or 26 extra-strength pills.

"Chronic severe alcoholics taking an overdose of acetaminophen are at greater risk than nonchronic alcoholics," Rumack says. "The person who has three drinks a day -- the one the Tylenol label warns to call a doctor -- is not at changed risk. If that person takes an overdose, they are at the same risk as anyone else. But a chronic alcoholic taking an overdose is clearly at higher risk."

More Study Needed

The fact that this argument continues shows that more research is needed, Anania says.

"For all we know, the increase in acetaminophen-related liver toxicity that Dr. Lee is seeing may be that fatty liver may lead to obese people not being able to deal with the drug," he says. "But we have not dealt with that yet. There is a lot of information lacking on the part of doctors, the FDA, and the industry."

And in addition to more research, Anania has three words of advice for both patients and doctors.

"Education, education, education. That's what we need," he says. "This is a debate that has been going on for a long time. I don't think restricting Tylenol is the answer. There is a need for education and better labeling. And education of physicians would help, too."

Show Sources

SOURCES: Lee, W.M. Hepatology, July 2004; vol 40: pp 6-9. Rumack, B.H. Hepatology, July 2004; vol 40: pp 10-15. Frank A. Anania, MD, director of hepatology, Emory University School of Medicine. Barry H. Rumack, emeritus director, Rocky Mountain Poison and Drug Center; professor of pediatrics, University of Colorado School of Medicine.

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