The Food and Drug Administration will limit the amount of the pain reliever acetaminophen allowed in commonly used prescription drugs such as Percocet and Vicodin to reduce the danger of harm to the liver.
But Thursday’s announcement, setting a maximum of 325 milligrams per prescription pill, will not affect over-the-counter products containing acetaminophen, which is best known by the brand name Tylenol.
The FDA also will require box warnings — its strongest labeling requirement — about possible liver damage on acetaminophen prescription products.
Acetaminophen is usually paired with painkilling opioids like hydrocodone or oxycodone and such combination products are prescribed nearly 200 million times per year, making them among the most widely used prescription drugs.
Acetaminophen is valued as a pain reliever in part because, unlike other common analgesics such as aspirin, ibuprofen and naproxen, it does not cause gastric bleeding or other stomach discomfort.
But regulators have long worried about liver damage from the drug, particularly when taken in excess of a 4,000-milligram daily limit or with alcohol.
Acetaminophen overdose is the leading cause of liver failure and the leading cause of death from liver failure in the U.S. Overdoses accounted for 56,000 hospital emergency room visits and were linked to an average of 458 deaths annually during the 1990s, according to FDA data.
Avoiding overdose can be challenging because the drug is blended into so many cold preparations and pain relievers.
The FDA is not taking any action affecting the levels of opioids in the drugs, and the lowering of the acetaminophen dosage won’t affect their pain-relieving quality, said Sandra Kweder, a senior official in the FDA’s drug office, who briefed reporters on the changes.
“We don’t believe we are making these products less effective,” said Kweder, who noted that the combination drugs were introduced with lower doses of acetaminophen that crept upward over time.
The elimination of versions of drugs containing up to 750 milligrams of acetaminophen will be phased in over three years and is not expected to create shortages of pain medication.
While the FDA’s action will lessen the strain of acetaminophen-opioid combinations on the liver, it may have the unintended consequence of increasing abuse of the drugs, said Frank Palumbo, director of the University of Maryland’s Center for Drugs and Public Policy.
“I think it’s a double-edged sword,” Palumbo said. “Some patients may be tempted to take more of the opioid.”
The FDA’s restrictions are less stringent than the suggestions of an agency advisory committee, which by a narrow margin in July 2009 recommended a ban on Percocet and Vicodin.
Kweder said limiting the amount of acetaminophen was “a more reasoned and reasonable” approach that would not disrupt pain management programs.
In a statement, Abbott Laboratories, the maker of Vicodin, said it was “evaluating the FDA’s guidance and will determine how best to comply.”
One prescription drug containing acetaminophen, known by the Darvocet brand name, was removed from the market at the FDA’s request in November because of concerns about the heart toxicity of propoxyphene, the other active ingredient in the product.
Elimination of acetaminophen in higher dosages in prescription compounds means that it will be available on its own in a higher strength — 500 milligrams — in both over-the-counter and prescription versions.
The 2009 advisory committee recommended imposing a maximum strength of 325 milligrams for over-the-counter acetaminophen, but Kweder said the FDA hadn’t decided what actions, if any, it would take.
Sidney Wolfe, director of the nonprofit Public Citizen’s Health Research Group and a member of the advisory committee, lauded the FDA for its action on prescriptions, but he said the agency also should have restricted the size of over-the-counter doses because they make up 80% of the acetaminophen market.