Clearer Liver Warning Urged for Painkillers

Tylenol maker says it plans to add one to label

By Adam Marcus
HealthScoutNews Reporter

http://www.drkoop.com/template.asp?page=newsdetail&ap=93&id=509224

FRIDAY, Sept. 20 (HealthScoutNews) -- Experts are urging the federal

government to mandate clearer and more consistent warning labels for acetaminophen, and the nation's leading maker of the pain and fever remedy has announced it is ready to do so.

Concerned that many Americans accidentally take toxic doses of acetaminophen, a Food and Drug Administration advisory panel yesterday overwhelmingly recommended that the agency force manufacturers to state boldly that misuse of the ubiquitous product can be deadly.

The panel said the risk of liver damage associated with acetaminophen, the active ingredient in Tylenol and its knockoffs, was great enough to warrant the change. Overdoses of acetaminophen, both intentional and accidental, are among the most common causes of adverse drug reactions in the world, experts said.

The makers of Tylenol, the best-selling acetaminophen product, plan to add a message on the warning label saying the drug can damage the liver.

The FDA has determined that acetaminophen overdoses lead to more than 56,000 emergency room visits a year in the United States, many involving infants and young children. Of those, about a quarter are unintended, and 100 are deadly.

"The fear is that people don't realize how many products contain acetaminophen," said Laura Bradbard, an FDA spokeswoman. Someone might take Tylenol for pain, then a cold remedy in the same day but not know they're exceeding the maximum safe dose. Acetaminophen is found in nearly 200 over-the-counter products, as well as some prescription painkillers like Percocet and Darvocet.

Bradbard said some babies die every year because parents give them liquid acetaminophen instead of solutions that come in droppers and are prepared specially for infants. The two contain different concentrations of medication, but warning labels don't offer concrete guidance for how much is appropriate for babies.

Acetaminophen packaging already bears a variety of warnings. Some bottles advise consumers not to take the painkiller with other products, like cold remedies, that include it. Others caution about the risk of combining the medication with three or more drinks a day of alcohol, while others state that liver damage is a side effect.

The FDA panel said it wanted to see a clearer warning that liver damage could result from overdose independent of heavy alcohol consumption.

The top recommended doses of acetaminophen are 4 grams a day -- that's eight extra-strength tablets -- for adults and 90 milligrams per kilogram a day for children. A single dose of 150 mg per kilogram, or about 7 grams, is considered poisonous to the average adult.

Those with a history of alcohol abuse or other liver trouble may suffer harm at lower amounts. Fasting, such as loss of appetite from a viral illness, also appears to be factor in overdoses and liver harm, experts said.

Dr. Susan Farrell, a toxicologist at Brigham and Women's Hospital in Boston, said high doses of acetaminophen are broken down by the liver into a toxic form that can harm the organ. However, the damage is reversible if it isn't deadly. Farrell agreed with the panel that "probably there needs to be better" labeling to reflect the hazard.

Dr. Anthony R. Temple, vice president of medical and regulatory science for McNeil Consumer & Specialty Pharmaceuticals, which makes Tylenol, said the company would soon change its packaging to say the medication "may cause liver damage. That makes it more specific to the type of health problems that may occur," said Temple. He added that acetaminophen is "the safest of all the [non-prescription] pain relievers if you take it at the recommended dose."

Temple said McNeil voluntarily put a warning on its Tylenol packaging about the hazards of alcohol and acetaminophen in 1994, four years before the FDA made such wording mandatory.

The FDA isn't bound by its panel recommendations, and rarely ignores them. However, the panel has made a similar recommendation in the past, and the FDA never acted on it. It has been trying to issue a report on the side effects of acetaminophen and other nonprescription painkillers for many years.

Today the same FDA panel took up the issue of whether to strengthen the warning labels on aspirin and other nonprescription, nonsteroidal anti-inflammatory drugs (NSAIDS), like ibuprofen. In particular, the agency is looking at the risks of gastric bleeding and kidney failure linked to the compounds. Aspirin and its relatives are thought to cause as many as 16,500 deaths a year from stomach and intestinal problems.