🚀 go-pugleaf

100 people a year die from acetaminophen, perhaps it's time for 
some acetaminophen contols. Why isn't the government protecting 
us?! ;-)

http://www.medpagetoday.com/Gastroenterology/GeneralHepatology/tb
/2233?pfc=101&spc=230

Acetaminophen Is Leading Cause of Acute Liver Failure
  	
By Neil Osterweil, Senior Associate Editor, MedPage Today
Reviewed by Robert Jasmer, MD; Assistant Professor of Medicine, 
University of California, San Francisco
November 30, 2005

 SEATTLE, Nov. 30 - Liver toxicity from acetaminophen poisoning 
is by far the most common cause of acute liver failure in the 
United States, researchers reported.

Users of the popular painkiller who are most at risk include 
those with depression, chronic pain, alcohol/narcotic use, and 
those who take several acetaminophen-containing products at the 
same time, they added.

"Education of patients, physicians, and pharmacists to limit 
high-risk [acetaminophen] use settings is recommended," wrote 
Anne M. Larson, M.D., of the University of Washington, and 
colleagues at 21 other U.S. centers, in the December issue of 
Hepatology.

Acetaminophen (Tylenol and generics) is widely available in over-
the-counter preparations for headaches, colds, allergies, 
osteoarthritis, and other conditions.

The data suggest that consistent use of as little as 7.5 g/day of 
acetaminophen could lead to severe hepatic injury, Dr. Larson and 
colleagues wrote.

But in an accompanying editorial, John G. O'Grady, M.D., of the 
Institute of Liver Studies at King's College Hospital in London 
cautioned that there's no need for panic, because acetaminophen-
associated liver toxicity is uncommon, and the drug itself is not 
toxic.

"Measures to minimize acetaminophen hepatotoxicity are important 
but need to be considered in the context that the apparent scale 
of the problem is a reflection of the huge number of patients 
taking acetaminophen with good effects and in the absence of any 
adverse event," Dr. O'Grady wrote.

"Educational initiatives to highlight the range of preparations 
containing acetaminophen, together with reiteration of advice on 
maximum daily dosing, have potential benefits, especially with 
respect to unintentional overdosing," he added.

Acetaminophen overdose -- anything more than the package-
recommended 4 g/day -- has been associated with severe hepatic 
necrosis leading to acute liver failure. Some people deliberately 
take toxic doses in suicide attempts, but others may accumulate 
high levels of acetaminophen unintentionally when they take, for 
example, Tylenol for a headache and a second acetaminophen-
containing product for cold symptoms.

Although N-acetylcysteine administered with 12 hours of ingestion 
of acetaminophen can prevent liver injury, many people may be 
unaware that they could benefit from it, Dr. Larson and 
colleagues wrote.

"Unintentional overdosing is usually only recognized after 
symptoms have developed. Extended acetaminophen dosing, delay in 
seeking medical attention, and/or failure to institute N-
acetylcysteine therapy are associated with greater morbidity and 
mortality," they noted.

To determine whether people who inadvertently overdose on 
acetaminophen are at greater risk for bad outcomes, Dr. Larson 
and colleagues at 22 U.S. tertiary care centers examined the 
incidence, risk factors, and outcomes of acetaminophen-induced 
acute liver failure in consecutive patients seen over a six-year 
period.

They found that 662 patients met the established acute liver 
failure criteria of coagulopathy and encephalopathy, and that 42% 
of these patients (275) had liver failure associated with 
acetaminophen liver injury.

They also noted that the annual percentage of acetaminophen-
related failures rose during the study period. Acute liver 
failure related to use of the painkiller accounted for 28% of all 
cases in 1998, and 51% in 2003.

The median dose ingested by participants in the study was 24 g 
(range 1.2-180 g). The 24 g dose is the equivalent of 48 extra-
strength tablets, the authors noted.

Suicide attempts accounted for 122 of the 275 cases (44%), 
unintentional overdoses accounted for 131 (48%) of the cases, and 
the remaining 22 (8%) were of unknown intent.

Among those who didn't intend to overdose, 38% had taken two or 
more acetaminophen-containing products simultaneously, and 63% 
used narcotic-containing compounds such as Percocet 
(acetaminophen and oxycodone) or Vicodin (acetaminophen and 
hydrocodone).

Eighty-one percent of patients in this group reported taking an 
acetaminophen and/or other analgesics for acute or chronic pain 
syndromes.

"Overall, 178 subjects (65%) survived, 74 (27%) died without 
transplantation, and 23 subjects (8%) underwent liver 
transplantation; 71% were alive at three weeks," the 
investigators wrote.

Both the transplant-free survival rate and rate of liver 
transplantation were similar between intentional and 
unintentional overdoses.

Both the study authors and editorialist suggested that a strategy 
restricting but not banning over-the-counter sales of 
acetaminophen containing medications may be necessary to prevent 
accidental overdoses.

"This approach was taken in the United Kingdom in 1998, when 
over-the-counter sales of acetaminophen were restricted to 16 
g," he wrote. "In the four years following the change in 
legislation there was a 30% reduction in patients with severe 
acetaminophen-induced acute liver failure admitted to specialist 
liver units and liver transplant centers."

In France, where only half that much acetaminophen can be bought 
at one time "this measure is highly effective in minimizing 
severe acetaminophen hepatotoxicity," Dr. O'Grady added.

Primary source: Hepatology
Source reference:
Larson AM et al Acetaminophen-Induced Acute Liver Failure: 
Results a United States Multicenter, Prospective Study. 
HEPATOLOGY 2005;42:1364-1372.