"While this is not an industrywide initiative at this time, it fits squarely within the many ongoing industrywide educational initiatives to further acetaminophen safe and responsible use by consumers," said Emily Skor, a vice president with the trade group, which represents McNeil, Bayer Healthcare, Procter & Gamble and other nonprescription drugmakers.
20 YEARS OF WARNINGS
McNeil has updated the safety warnings on Tylenol periodically since the 1990s.
In 1994, the company added a warning about the risk of liver damage when combining alcohol with Tylenol following a lawsuit brought by Antonio Benedi, a former aide to President George H.W. Bush, who fell into a coma and underwent emergency liver transplant after mixing Tylenol with wine at dinner.
A jury awarded him $8.8 million in damages after concluding that McNeil failed to warn consumers about the risk. The FDA made the alcohol warning mandatory for all manufacturers of acetaminophen in 1998.
Then, in 2002, an expert panel of FDA advisers recommended that the government agency require all acetaminophen products to carry a warning about the risk of "severe liver damage" when not taken as directed. The group's votes are non-binding, though the FDA usually follows them. McNeil voluntarily added the warning to its products in 2004, five years before the FDA made it mandatory.
Today, McNeil appears to be moving ahead of regulators again. In 2009, the FDA assembled another expert panel to consider more sweeping changes to reduce acetaminophen overdoses. The panel recommended a half-dozen major changes, including lowering the maximum nonprescription daily dose for adults. McNeil voluntarily adopted that recommendation, lowering the recommended adult dose of Extra Strength Tylenol to 3,000 milligrams per day, or six pills of Extra Strength Tylenol, down from 4,000 milligrams per day, or eight pills. The label stipulates that patients can still take a higher dose under doctor's directions.
But the company has not embraced a more drastic recommendation by the FDA's expert panel: eliminating the over-the-counter "extra-strength" formulation altogether, which would mean lowering the acetaminophen dose from 1,000 milligrams to 650 milligrams, or two tablets of 325 milligrams each. The panel said the 1,000 milligram dose should only be available via prescription.
McNeil argues that the lower dose is less effective and could drive people to take anti-inflammatory pain relievers, a different class of drugs that includes aspirin and ibuprofen. Those medicines can cause stomach ulcers and dangerous gastrointestinal bleeding.
FDA spokeswoman Erica Jefferson says the agency is actively working on new rules for both children and adult acetaminophen products. While the agency won't give a timeframe for completion, the federal government's website that tracks new regulations lists December as the target date for publishing the proposed rules.
As early as 1977, FDA advisers recommended adding more warnings to the acetaminophen label about liver damage, but the agency didn't require the language until 2009.
"They are very slow to respond to these things and it's always a little frustrating," says Dr. Lewis Nelson of New York University, who chaired the 2009 FDA panel.
ANATOMY OF AN OVERDOSE
Experts first identified acetaminophen overdose as a major public health concern in the 1990s, but it has taken years to form a clearer picture of the problem.
Acetaminophen overdoses occur when the liver is overwhelmed by too much of the drug, producing a toxic byproduct that kills liver cells. Liver failure occurs when most cells are no longer able to function. At that point, a patient then generally has 24 to 48 hours to live without a transplant.
Of the roughly 500 acetaminophen deaths reported annually, about half are accidental, with the rest deemed suicides. About 60 percent of the unintentional overdoses involve prescription opioid-acetaminophen combination drugs such as Percocet and Vicodin, according to a database of liver failure cases run by Dr. Lee at the Southwestern Medical Center in Dallas. Those two products alone were prescribed more than 173 million times last year, according to IMS Health.