FDA probes new worry about acetaminophen overdose

March 27, 2001

WASHINGTON (AP) -- Evidence that many Americans may poison their
livers by unwittingly taking toxic doses of acetaminophen has the
government considering if consumers need stiffer warnings about the
popular over-the-counter painkiller.

It's not the first time acetaminophen, best known by the Tylenol
brand, has drawn federal concern. There are warnings not to take it
if you consume more than three alcoholic drinks, because the
combination can poison your liver.

But the latest worry is about overdoses: taking too much for too
long, or mixing the myriad acetaminophen-containing headache,
cold/flu and other remedies, or just popping extra pills.

Because acetaminophen is nonprescription, people think "it must be
safe and they take it like M&Ms," sighs Dr. William Lee of the
University of Texas Southwestern Medical Center in Dallas.

'Conspicuous' toxic effects

Lee's data suggest acetaminophen overdoses could be a bigger cause of
liver failure than some prescription drugs recently banned for liver
poisoning, such as the diabetes medicine Rezulin.

He tracked more than 300 acute liver failure cases at 22 hospitals
and linked 38 percent to acetaminophen, versus 18 percent of cases

caused by other medications. In a second database tracking 307 adults
suffering severe liver injury -- not full-fledged failure -- at six
hospitals, Lee linked acetaminophen to 35 percent of cases.

Most were accidents and should have been preventable, Lee contends.

The findings surprised Food and Drug Administration officials, who
this month began investigating how big a risk the painkiller poses
and whether Americans need more explicit warnings to use it safely.
They even are seeking data from Britain, where so many people used
acetaminophen for suicide that British health authorities now
restrict how many tablets are sold at once.

Acetaminophen's liver toxicity "is conspicuous in its magnitude
compared to some of the other bad players we've taken off the
market," says Dr. Peter Honig, FDA's postmarketing drug safety chief.
"We're looking at the data to decide if something has to be done, and

Certainly millions of Americans safely take acetaminophen every day.
Tylenol maker McNeil Consumer Healthcare calls it one of the safest
over-the-counter products and insists liver failure occurs only with
substantial overdoses.

"This is not a casual, 'Oops, I took an extra pill,"' stresses McNeil
vice president Dr. Anthony Temple.

Nor is it the first liver warning. The FDA mandates that bottles bear
alcohol warnings, after a Virginia man won an $8 million lawsuit
claiming moderate Tylenol doses with his usual dinner wine left him
needing a liver transplant.

And McNeil warns that mixing up doses of infant Tylenol drops with
children's Tylenol liquid kills -- the two are not interchangeable.
Yet poisonings still occur when parents mix up products and give
babies a potentially deadly teaspoon-full instead of a safe

More explicit warnings sought

For adults, acetaminophen bottles recommend no more than eight
extra-strength pills in 24 hours, and to seek help for overdoses.

Critics want labels to mention liver failure explicitly, saying
consumers don't realize overdosing is easy and dangerous. Lee cites
taking maximum doses for days instead of once or twice, or flu
sufferers taking high doses while not eating. Some rack up the
chemical by taking acetaminophen-containing prescription painkillers
like Vicodin or Percocet plus over-the-counter headache or cold/flu
remedies. Also, there are reports that smaller acetaminophen doses
may overwhelm hepatitis sufferers.

On the other hand, some FDA officials worry that too-explicit
warnings could alert potential suicides to the worst doses, causing a
problem such as Britain faced.

To be safe, Lee advises limiting daily acetaminophen to the amount in
four extra-strength pills, 2 grams total from all medicines.

Overdoses can be treated easily if doctors know the culprit in time.
But initial symptoms are flu-like and doctors may not promptly test
for acetaminophen's hallmark sky-high liver enzymes.

Consider 23-year-old Marcus Trunk, who took prescription Tylenol with
codeine for a wrist injury for 10 days and then over-the-counter
acetaminophen for another week. Suddenly fever and vomiting struck. A
hospital initially gave more acetaminophen before diagnosing liver
failure, says his mother, Kate Trunk of Fort Myers, Florida. He died
in a week; an autopsy blamed acetaminophen.

Mrs. Trunk had thought that alcohol was acetaminophen's only risk and
said her son was a teetotaler. Today, her haunting thought: "If I'd
been more educated to acetaminophen products, could I have steered
him clear?"

Copyright 2001 The Associated Press.