The Oregonian

Plagued by nagging colds, sore backs, throbbing heads and life’s other aches and pains, millions of people reach for Tylenol.

And if one dose doesn’t stop the pain, maybe two or three will.

If you do that, you’re courting trouble: An overdose of acetaminophen, the popular painkiller in Tylenol and other brands, sends thousands of U.S. residents to the hospital each year, killing hundreds.

For years, fear of an acetaminophen overdose has been the main reason people call poison-control centers. It’s the leading cause of death in poison-control cases. Now, studies show overdoses of the drug have become the nation’s chief cause of acute liver failure, a rare but life-threatening crisis. Up to half of these poisonings appear accidental.

The federal government is considering more severe warning labels on over-the-counter acetaminophen drugs. Some brands have already made changes. And drug makers and regulators have launched campaigns to warn about the dangers of acetaminophen overdoses.

“We take this seriously,” said Dr. Ed Kuffner, senior director of medical affairs for Tylenol maker McNeil Consumer Healthcare. “Nobody should ever exceed 4,000 milligrams per day.”

Just twice that maximum dose increases your risk of liver failure. The daily maximum equals eight Extra Strength Tylenols, so using 15 pills a day can be dangerous – even once. The maximum doesn’t change if you mix products. Doctors worry some overdoses stem from people who combine several of the 600-plus-milligram acetaminophen drugs and don’t realize how much they’re ingesting.

For example, if you take two Vicodin, two Excedrin and drink a Theraflu packet, you can get as much as 3,150 milligrams of acetaminophen, close to the daily maximum, depending on which of those brands’ products you use.

The basic message: Know what’s in the drugs you take and follow instructions on the label.

“It’s a good product. … But it’s got to be used as directed,” Dr. Zane Horowitz, medical director of the Oregon Poison Center, said of acetaminophen. “Kind of like a stepladder. If you use it correctly, it’s a great thing. If you step on that tippy-top step, you’re going to fall off.”

At recommended doses, acetaminophen rarely causes problems, unless you are hypersensitive or have serious liver problems. If you regularly have three or more alcoholic drinks in a day, you may form problems at lower doses of acetaminophen or other painkillers, though studies conflict on whether this problem is real or just a theory.

The fact that acetaminophen is safe and works for most users helped make it the nation’s most popular medicine.

About a fifth of U.S. adults, or 45 million people, take acetaminophen in any week, a survey by the Slone Epidemiology Center at Boston University says. Nearly 10 percent of U.S. residents under 18 take acetaminophen in any week, roughly 7 million kids.

Nearly all those uses are safe. But high doses can cause problems because the liver makes a toxic chemical as it works to process the drug. In most cases, the liver corrals and clears out that toxin. But if the dose rises too high, the liver can be poisoned, toxins can build in the body, the brain may swell, and people can fall into a coma and die. These serious overdoses can creep up: A person may feel fine, maybe just nauseated, for a day or two before the crisis hits.

This might mean it’s easier to have a life-threatening dose of acetaminophen than some other common painkillers, doctors said. But they added that drugs such as ibuprofen, which can kill at bigger doses, may cause more side effects at recommended doses, including stomach irritation.

Acetaminophen was the reason for 133,000 calls to U.S. poison-control centers in 2004. More than half of those cases needed treatment in a health care facility. And 327 people died in 2004, more than a quarter of all the deaths in poison-center cases.

Emergency doctors can treat acetaminophen overdoses in the first 12 to 24 hours. After that, the antidote, a foul-tasting drug that helps the liver clear toxins, loses its effectiveness.

Overdoses increasingly cause acute liver failure, a disastrous organ collapse that hits quickly. Years ago, hepatitis was the main cause of this life-threatening condition, which strikes about 2,000 U.S. residents each year. But acetaminophen is now the No. 1 cause, said the University of Washington’s Dr. Anne Larson, main author of a December study that involved 22 hospitals.

Acetaminophen caused 42 percent of the acute liver failures in the 1998-2003 study, including 51 percent in the final year. In 275 acetaminophen overdoses, 74 people died and 23 got transplants. Roughly half of acetaminophen overdoses seemed accidental. Those patients said they took an average of 7,500 milligrams a day, usually for less than a week.

“That really, I think, is the striking thing,” said Oregon Health and Science University’s Dr. Atif Zaman, who worked on the study. “There are people thinking, “Well, if I take one, and it helps, I could take two.”‘

Health experts hope to alter that thinking. In 2002, a committee advised the Food and Drug Administration to change the labels on all over-the-counter drugs containing the painkiller. They said “acetaminophen” should be in large, bold type on labels and that regulators should consider warning consumers specifically about liver damage. A spokeswoman said the FDA is working on a proposed rule but has no time line.

Some drug makers are not waiting. McNeil already made the word “acetaminophen” bigger on labels and started using it in more Tylenol ads, Kuffner said. The company expanded label warnings, telling people not to use it “with any other product containing acetaminophen” and saying overdose “may cause liver damage. In case of overdose, get medical help or contact a Poison Control Center right away … even if you do not notice any signs of symptoms.”

Consumers can take several steps to protect themselves and loved ones, doctors said. That includes reading the labels of every drug taken, by prescription and over the counter, and following the directions.

Pay attention to children’s products, whose concentration varies widely: A teaspoon of Tylenol Children’s Suspension Liquid has 160 milligrams of acetaminophen. A teaspoon of Infants’ Tylenol Concentrated Drops, meant for use in smaller doses, has 500 milligrams. Don’t substitute one for the other, doctors said.

If you take several drugs, be careful to check their total acetaminophen dose and make sure there are no other problems. That can be hard to figure out, so those unsure about safe use should call a doctor, pharmacist, poison center or the hot lines listed on some drug boxes.

“Really, with most drugs, the best thing to do is use the smallest amount, but make sure it’s an effective amount,” Zaman said. “Stay away from the adage “More is better.”‘

PH END DWORKIN

(Andy Dworkin is a staff writer for The Oregonian of Portland, Ore. He can be contacted at andydworkin(at)news.oregonian.com.)

AP-NY-06-01-06 1628EDT