FDA Advisory Panel Urges "Black Box" Warning -- and Potential Ban -- on Prescription Acetaminophen Combinations Due to Liver Toxicity

By Liz Highleyman

Acetaminophen toxicity is a leading cause of acute liver failure, accounting for an estimated 50,000 emergency room visits and nearly 500 deaths annually in the U.S., according to the American Association for the Study of the Liver

The drug can cause acute liver failure at amounts not much higher than the standard recommended maximum dose -- or even at the recommended dose in some individuals. People with pre-existing liver disease such as chronic hepatitis B or C are at higher risk, as are people who drink alcohol while taking the drug.

Acetaminophen is an ingredient in so many different over-the-counter and prescription products that people may accidentally overdose. The concern with the prescription combinations -- widely-used pain relievers combining acetaminophen with hydrocodone (Vicodin), oxycodone (Percocet), or codeine (Tylenol 3) -- is that patients may take too much acetaminophen when they increase the dose in an effort to get more of the coformulated narcotic.

The joint panel of the FDA's Drug Safety and Risk Management Advisory Committee, Nonprescription Drugs Advisory Committee, and Anesthetic and Life Support Drugs Advisory Committee held 2 days of hearings on the issue of acetaminophen liver toxicity and how to prevent it.

The panel voted nearly unanimously (36 to 1) to require the "black box" warning on prescription product labels. However, a proposal to ban the prescription combinations was more controversial (20 to 17 in favor), as was a move to ban acetaminophen-containing over-the-counter products (24 to 13 against).

The panel also considered whether to require a single dose of acetaminophen in liquid products for children in order to avoid confusion (36 to 1 in favor), lower the maximum recommended daily and single doses (21 to 16 and 24 to 13 in favor, respectively), make the current 500 mg extra-strength version available by prescription only (26 to 11 in favor), and sell acetaminophen in smaller packages with fewer pills, as done in the U.K. -- an attempt to prevent massive intentional overdosing as a suicide attempt (20-17 against).

The potential ban is more controversial than the label warning since removing prescription acetaminophen combinations from the market would leave few analgesic options outside the strictly regulated Class II narcotics -- which, though actually safer in many respects, have much more stringent requirements for both prescribing physicians and patients.

The FDA is not required to follow the advice of advisory committees, but it usually does so.

7/3/09

Sources

FDA Panel Backs 'Black Box' Warning for Acetaminophen Prescription Combos. MedPage Today. June 30, 2009

G Harris. Panel Recommends Ban on 2 Popular Painkillers. New York Times. June 30, 2009.