The debate over acetaminophen and acute liver failure

[Guest guest]

Public release date: 20-Jul-2004

Contact: Greenberg

dgreenbe@...

201-748-6484

Wiley & Sons, Inc.

The debate over acetaminophen and acute liver failure

One expert questions the acceptability of the current level of

acetaminophen-related injury and death, while another suggests that

acetaminophen overdoses are misunderstood

Acetaminophen overdose causes more than 450 deaths due to acute liver

failure each year in the United States and this number appears to be on the

rise. In 2001, the U.S. Acute Liver Failure (ALF) Study found acetaminophen

responsible for 39 percent of cases. In 2003, the number had risen to 49

percent.

M. Lee, M.D., of the University of Texas Southwestern Medical Center

in Dallas, Texas and a principal investigator of the NIH-funded U.S. Acute

Liver Failure Group, suggests that the FDA should consider a more aggressive

and broader approach toward regulating the pain reliever to lessen the

incidence of such poisonings. Lee's article is one of two in the July issue

of Hepatology that considers acetaminophen-related injury and death in the

U.S.

Hepatology, the official journal of the American Association for the Study

of Liver Diseases (AASLD), published by Wiley & Sons, Inc. is available

online via Wiley InterScience at

http://www.interscience.wiley.com/journal/hepatology.

A counterpoint article, by Barry H. Rumack, M.D. of Rocky Mountain Poison

and Drug Center at the University of Colorado, says that therapeutic doses

of the drug do not place patients at risk, even when factors such as fasting

and alcohol consumption are considered. He suggests that most

acetaminophen-related injuries and deaths may be due to intentional

overdose.

More than 50 percent of the country's cases of acute liver failure are

related to acetaminophen, according to the ALF Study, reports Lee. While

acetaminophen overdose is a fairly common way to attempt suicide, most

suicidal patients receive medical care within four hours and can be

protected by the acetaminophen antidote.

However, Lee reports that people who ingest large quantities of the drug

over several days ­ usually to relieve pain and often in conjunction with

other narcotics ­ are typically not aware of the potential harm and only

seek treatment after symptoms of toxicity have appeared and their prognosis

is poor. These unintentional cases constitute roughly half of all cases that

develop liver failure and 30 percent of all these cases are fatal.

" We must remain skeptical of 'accidental' or 'unintentional' overdosages in

adults, " writes Rumack. He suggests that cases recorded as unintentional may

have actually been suicide attempts. " It is not possible to calculate the

true rate, as we do not know how many patients took overdosages and did not

seek treatment nor how many misrepresented what they actually did, " he says.

The U.S. Food and Drug Administration regulates acetaminophen, and in 2002,

its Non-prescription Drugs Advisory Committee considered evidence on related

acute liver failure. The committee recommended changing package labeling to

include a prominent warning that excess quantities of the drug might lead to

liver injury and requiring the display of the generic name on the front of

the package to avoid accidental overdose from the use of multiple

acetaminophen-containing products. However, the FDA has not yet acted on

that recommendation.

When the United Kingdom began aggressively working to limit acetaminophen

overdosing by limiting available quantities and requiring blister packaging,

the country saw a 10 percent decline in related hospital admissions, a 19

percent reduction in related deaths and a 56 percent reduction in related

liver transplants. In this country, a similar limit to package size and the

use of blister packaging might prevent a significant number of overdoses,

says Lee.

" Changing more than the package label would also send the message that this

medicine, like most others, is not globally safe, as its marketers claim, "

he says. " For a pain reliever with only mild-to-moderate efficacy, it would

seem prudent to move toward limiting these needless deaths. "