The percentage of cases of acute liver failure caused by an overdose of acetaminophen increased considerably from 1998 to 2003, with unintentional overdose accounting for at least half of these cases, a new US study shows.

Acetaminophen, known in some countries as paracetamol, is the active ingredient in painkillers like Tylenol. Too much can cause serious liver damage

People with chronic pain, depression and those who abuse substances, including alcohol, may be particularly at risk for unintentional acetaminophen overdose, Dr. Anne M. Larson of the University of Washington in Seattle and colleagues report in the medical journal Hepatology.

“Efforts to limit over-the-counter packaging size and to restrict the prescription of narcotic-acetaminophen combinations (or to separate the narcotic from the acetaminophen) may be necessary to reduce the incidence of this increasingly recognized but preventable cause of acute liver failure in the United States,” Larson and her team write.

The researchers analyzed data on 662 consecutive patients treated for acute liver failure at 22 US tertiary care centers between 1998 and 2003. During that time, the annual percentage of acute liver failure cases due to acetaminophen rose from 28 percent to 51 percent.

Among the 275 cases determined to be acetaminophen-related, 48 percent were unintentional overdoses, 44 percent were suicide attempts, and intent was unknown in 8 percent. Many characteristics of the unintentional and intentional overdose groups were similar, while their clinical outcomes were not different.

Patients who unintentionally overdosed were older than those who attempted suicide, more likely to use several products containing acetaminophen and took longer to seek care after symptoms developed. Seventy-nine percent reported taking the medications for pain.

Depression was reported by 24 percent who unintentionally overdosed, compared with 45 percent of patients who intentionally overdosed.

“Overall, 178 subjects (65 percent) survived, 74 (27 percent) died without transplantation, and 23 subjects (8%) underwent liver transplantation,” Larson’s group found.

The investigators say there is a relatively narrow range between an effective dose of acetaminophen and a dangerous dose. They say that “consistent use of as little as 7.5 grams per day may be hazardous.” One extra-strength Tylenol tablet contains half a gram of acetaminophen.

In an editorial accompanying the study, Dr. John G. O’Grady of King’s College Hospital in London points out that a 1998 rule in the UK restricting over-the-counter sales of acetaminophen to 16 grams led to a 30 percent reduction in hospital admissions for cute liver failure related to the drug, and France’s rule limiting sales to 8 grams has also been effective.

“The required judgment from society, the medical profession, and other interested parties, is whether that level of restriction is too high a price to pay,” he concludes.

SOURCE: Hepatology, December 2005.