Too many people are dying or being hospitalized from accidental overdoses of acetaminophen--the active ingredient in Tylenol--and drug makers should print stronger warning labels on bottles of the drugs, federal scientists said Thursday.
At least 100 people die of accidental acetaminophen poisoning every year and another 15,000 make visits to an emergency room because they are simply not aware of the risks, a Food and Drug Administration advisory panel was told.
Although an estimated 100 million people take the drug every year in safety, taking more than eight extra-strength pills (4,000 milligrams) per day, or taking fewer pills while consuming alcohol, can cause severe liver damage and death.
"You cannot allow more innocent men, women and children to suffer," said Kate Trunk, whose 23-year-old son Marcus died of an accidental overdose. "Death is not an acceptable side effect."
McNeil Consumer & Specialty Pharmaceuticals, a unit of Johnson & Johnson Inc., has already strengthened the warning on the label of Tylenol and said Thursday that it will further upgrade the warning in the near future.
Tylenol's label says, "Overdose warning: Taking more than the recommended dose (overdose) can cause serious health problems."
The new label will say, "Taking an overdose may cause liver damage," Dr. Anthony Temple of McNeil told the panel. "We think others in the industry should follow."
The panel also recommended that the phrase "contains acetaminophen" should be present on the label in large bold type in all products containing it. As many as 200 over-the-counter products contain the drug, including headache remedies and cough-and-cold syrups. It is also present in a few prescription painkillers, such as Percocet and Vicodin.
Patients combining such drugs can now receive a dangerous dose of acetaminophen without realizing it. That is apparently how Marcus Trunk died. He was taking an over-the-counter version of acetaminophen for pain from a wrist injury, and unwittingly also took a flu remedy containing it.
"It seems obvious to me, from a labeling point of view, that someone should be able to buy something in the supermarket and know what's in it," said Dr. Nathaniel Katz of New Rochelle, N.Y., a member of the advisory panel.
The panel also advised clarifications of dosages for infants. Several infants die each year when parents mistakenly administer children's liquid acetaminophen instead of infant acetaminophen drops. Labels on these products now tell parents to consult their physician about the proper dose. The panel suggested that proper doses should be printed on the label.
McNeil has applied to the FDA to make such a change, and the agency is considering it.
Acetaminophen has been available over the counter in the United States since 1960. Many physicians and patients prefer it because it has pain-relieving effects similar to aspirin but causes much less stomach distress.
But high doses of the drug can be lethal, and many people attempt suicide using the drug. An earlier FDA review found more than 41,000 emergency room visits every year by people who attempted suicide with acetaminophen.
The suicide problem became so severe in England that there are now restrictions on how many tablets of acetaminophen can be sold at one time.
In 1998, the FDA warned that people taking three or more alcoholic drinks per day should not take acetaminophen because of the high risk of liver damage when the two are combined.
FDA is not required to follow advice from its advisory panels, but it generally does so.
Earlier this week, scientists reported new research on how acetaminophen differs from aspirin. Aspirin and similar drugs work by inhibiting an enzyme called cyclooxygenase or COX. Ten years ago, researchers discovered that there are actually two forms of the enzyme, called COX-1 and COX-2.
COX-2 is the culprit responsible for pain, fever and inflammation, but COX-1 actually has a positive effect, protecting the stomach and gastrointestinal tract from acid. Aspirin has adverse effects on the stomach because it inhibits both enzymes. That discovery led to the development of a family of pain relievers called COX-2 inhibitors, such as Celebrex and Vioxx, which do not cause stomach problems.
On Monday, biochemist Dan Simmons of Brigham Young University reported that there is actually a third enzyme in the family, called COX-3. This enzyme is the target of acetaminophen, he said.