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DDW: Hepatitis Patients at Risk for Accidental Acetaminophen Toxicity
By Peggy Peck, MedPage Today Staff Writer
Reviewed by Robert Jasmer, MD; Assistant Professor of Medicine, University of
California, San Francisco
May 22, 2006
LOS ANGELES, May 22 - Over-the-counter flu remedies such as Nyquil or Theraflu
are often used for relief of the flu-like symptoms of acute hepatitis, a choice
that may trigger acute liver failure because those agents contain acetaminophen.
Serum samples from 72 patients with fulminant hepatitis detected evidence of
acetaminophen toxicity in 12.5% of patients, said William M. Lee M.D., of the
University of Texas Southwester Medical Center in Dallas, who reported the
findings at Digestive Disease Week sessions here today.
Dr. Lee and colleagues used a high-pressure liquid chromatography with
electrochemical detection to assess acetaminophen levels. They studied 10
patients with liver failure due to confirmed acetaminophen overdose as a
positive control group.
The average serum concentration of acetaminophen adducts was 0.45 nmol/mL versus
5.58 nmol/mL in the control group. Nonetheless, Dr. Lee said the evidence of
acetaminophen adducts was "a second insult to the liver cells on top of
hepatitis."
Importantly, the toxicity occurred when the patients used the over-the-counter
flu medicines at therapeutic doses. "None reported doses that would exceed 4
g/day," he said. That is lower than previously reported toxic doses, he said.
Acetaminophen toxicity occurs in a dose-related fashion. Seven or eight grams
consumed over the course of three to four days can be fatal, Dr. Lee said.
An online check of ingredients in cold and flu products found acetaminophen
listed as an ingredient in 26 OTC remedies, including Coricidin D, Triaminic,
NyQuil, DayQuil, and Dristan as well as Midol and Pamprin.
In this series, 67% of patients who had detectable acetaminophen-protein adducts
in their blood died within three weeks of hospital admission versus 27% of
patients who had no evidence of acetaminophen use (P=0.017).
Liver toxicity is a well known side-effect of acetaminophen, he said, noting
that acetaminophen overdose is a leading cause of liver failure and liver
transplants "I am surprised it is still on the market," Dr. Lee said.
He later qualified that statement saying that but the drug is so popular, and is
sold under so many different brands-the most popular being Tylenol-that he
doubts it would ever be removed from the market.
That said, he noted that people with liver disease are frequently unaware that
they are using acetaminophen-containing compounds, which could put them at risk
for liver failure.
"Vicodin and Percocet are the two most popular prescription compounds containing
acetaminophen and these are often prescribed for pain relief in people with
liver disease," he said. "Unbundling of both of these drugs, which might be done
at some point, would be significant in terms of reducing accidental
acetaminophen overdose."
He said that in 2002 a FDA advisory committee recommended that labels of
over-the-counter cold and flu medicines be changed so that the front label would
list acetaminophen as an ingredient. "But that was in 2002 and the FDA has yet
to act on that recommendation."
John M. Vierling, M.D., president of the American Society for the Study of Liver
Diseases, a professor of medicine at Baylor in Houston, said the hallmarks of
acetaminophen toxicity are "a change in mental state and alteration in clotting
ability."
Dr. Vierling called acetaminophen an "excellent drug" but added that Dr. Lee's
study suggests the need to advise patients with chronic liver disease to avoid
not only Tylenol and other acetaminophen products but also to be cautious when
selecting cold and flu medicines.
The patients were included in the National Institutes of Health Acute Liver
Failure Study (1999-2004), a national registry of acute liver failure cases. Dr.
Lee said there are roughly 2,000 cases of acute liver failure annually and about
500 of those are fatal.
http://www.medpagetoday.com/2005MeetingCoverage/2005DDWMeeting/dh/3349