Unintended acetaminophen overdoses rising

Penny Tenzer, MD, a family physician in Miami, occasionally sees a patient with elevated liver enzymes linked to taking too much acetaminophen. But unlike the majority of people who overdose on this drug, these patients were not deliberately trying to harm themselves. Rather, they took various over-the-counter medications without realizing that they all contained this ingredient.

"People are frequently so unaware of the many things that have acetaminophen in them and that there is a maximum daily dose," said Dr. Tenzer, who is the vice chair of the Dept. of Family Medicine at the University of Miami School of Medicine.

The fact that acetaminophen taken at higher than recommended doses can harm the liver is not new, and the possibility that this drug could be used to attempt suicide has long been acknowledged. Drug safety experts are increasingly recognizing, however, that not all overdoses are deliberate, and that this is a serious public health issue.

"We need to take a fresh look at patients who may be overusing acetaminophen," said Robert Gillette, MD, a retired family physician in Poland, Ohio, and one of the contributing authors of the American Academy of Family Physicians 2002 monograph, "Appropriate Use of Common OTC Analgesics and Cough and Cold Medications."

More recently, a Food and Drug Administration analysis of several national databases published online in Pharmacoepidemiology and Drug Safety last month found that the rate of overdoses classified as inadvertent ranged from 8% to 26%, depending on the dataset used. A study published in Hepatology prospectively followed several hundred patients with acute liver failure over six years. For those whose conditions were associated with high amounts of acetaminophen, 48% of the doses were inadvertent.

"We were impressed with how many were accidental," said Anne Larson, MD, lead author and associate professor in transplant hepatology at the University of Washington in Seattle. "It's touted as so safe, but acetaminophen has a narrow window for safety."

No one is calling for this drug to be removed from the market. In light of the millions who take it every day without incident, the percentage of adverse events is actually quite small.

"It's got to be one of the safest meds we have, despite this very real issue," said Jerry Avorn, MD, a pharmacoepidemiologist and professor of medicine at Harvard Medical School, who has written extensively on drug safety.

What those concerned with drug safety are calling for is better labeling and increased education for physicians, patients and the community at-large, particularly because it appears that this problem is getting worse. The FDA paper found that the number of fatalities from acetaminophen nearly doubled from 1997 to 2001, and the agency launched its own educational campaign in 2004. Dr. Larson's study also found that the percentage of acute liver failure due to the drug rose from 28% in 1998 to 51% in 2003.

"It's comes down to education of all physicians, patients and whole communities," Dr. Tenzer said.

Experts say clearer labeling is especially crucial, because these increases often are attributed to the fact that acetaminophen is in an ever-growing list of over-the-counter and prescription medications. At last count, more than 600 included it as an active ingredient, and the concern is that related precautions are not always clearly spelled out on the label.

"It's contained in so many different products, and the labeling is so poor, that even a reasonable patient has a hard time being able to steer clear of the maximum," Dr. Avorn said. "The warnings can be made far more patient-friendly."

A statement issued by McNeil Consumer & Specialty Pharmaceuticals, the company that manufactures acetaminophen under the brand name Tylenol, said work was continuing to improve the label.

"McNeil is committed to consumer safety and has a long history of pioneering labeling and packaging changes to reduce the potential for misuse of over-the-counter and prescription products," the statement read.