Earlier this week, the U.S. Food and Drug Administration urged health care providers to stop writing prescriptions for pain relievers containing more than 325 milligrams of acetaminophen, the active ingredient in Tylenol.
The agency’s announcement was aimed primarily at popular prescription medicines that combine acetaminophen with a more powerful opioid such as hydrocodone. Agency officials said they had determined that “there are no available data” to show that the benefits of having more than 325 milligrams of acetaminophen in a single pill outweighed the risks from taking too much of the drug.
The announcement followed up on a similar 2011 FDA admonition to drug makers and was the latest turn in a long-running deliberation over the regulation of acetaminophen.
As documented in a ProPublica series last year, the FDA has delayed for decades enacting tougher rules on acetaminophen. While generally considered safe when taken as recommended, relatively small overdoses have been shown to cause liver damage and even death. Each year, the drug accounts for about 150 accidental deaths, half of all cases of acute liver failure cases and tens of thousands of emergency room and hospital visits, according to federal data and scientific studies.
As far back as 1977, a panel of outside experts convened by the FDA recommended the agency set the standard dose of over-the-counter acetaminophen at 325 milligrams per pill, citing the possibility of liver damage. But the agency allowed 500 milligrams and even 650 milligrams single doses of the drug for sale. Today, the most commonly sold form of over-the-counter acetaminophen contains 500 milligrams in a single pill.
A 2008 FDA review found that the agency’s approval for such a dose was based on “few and limited” studies submitted in the 1970s by McNeil Consumer Healthcare, the Johnson and Johnson unit that makes Tylenol. Two studies showed that two 500-milligram pills were “marginally” more effective than two 325-milligram pills, while two other studies showed no difference.
Ninfa Redmond, a toxicologist who helped carry out the 1977 panel’s exhaustive, three-year study, said she was surprised that such big doses continued to be sold 40 years later.
“It never occurred to any of us that you make a product with that high a dose,” Redmond said. “I use the drug when I travel, but I use 325 milligrams,” she added.
Tuesday’s recommendation only applies to prescription drugs, not the over-the-counter products that make up about 80 percent of the market, according to the FDA. That means that you will still be able to walk into a gas station or grocery store and buy pills with up to 650 milligrams of acetaminophen, while your pharmacist is now discouraged from dispensing any product with more than half that amount.
One reason for this is that the FDA has more power to regulate prescription drugs than over-the-counter medicines.
In June 2009, an FDA advisory panel urged various limits on both over-the-counter and prescription drugs. But over-the-counter drug makers, led by McNeil, resisted efforts to reduce pill strength. In a 2009 letter to the FDA, McNeil noted that 500-milligram pills accounted for 92 percent of U.S. acetaminophen sales. McNeil suggested that removing the pills from the market would “burden” consumers by blocking access to pain relief.
The company also noted that reducing pill strength would require a “significant amount of time” in the over-the-counter regulatory system. If the agency decided not to pursue such a reduction, McNeil pledged it would add language to their drug labels recommending a lower total daily limit of 3,000 milligrams – or six extra strength pills.
“Other proposals could take significantly longer to implement,” wrote Lynn Pawelski, the company’s vice president for regulatory affairs.
In 2011 the company changed its label on Extra Strength Tylenol to reflect the lower recommended maximum daily dose.
McNeil, in an emailed statement, said the company still opposes any reduction in pill size for Extra Strength Tylenol and is committed to the health and safety of its patients.
“As the makers of Tylenol ... the health and safety of consumers is our number one priority,” the statement said. “Our position was on OTC medicines and that position has not changed.”
Even with prescription drugs containing acetaminophen, the FDA has moved slowly. In 2011, the agency warned manufacturers to stop making prescription pills with more than 325 milligrams by January 2014. In this week’s announcement, the agency said more than half of all drug makers had complied with the three-year deadline, but acknowledged that some continued to sell prescription combinations with more than 325 milligrams of acetaminophen.
ProPublica found that many of the largest pharmaceutical companies had dropped the amount of acetaminophen in their combination products to meet the FDA target, including the popular pain killer Vicodin, by AbbVie Inc.; Percocet, by Endo Pharmaceuticals; and Tylenol with Codeine, by the prescription drug unit of Johnson and Johnson.
In response to questions, the FDA was unable to say how many companies had failed to comply, or what percentage of the market they represented. The agency said it would now start to crack down on the remaining combination pills. “If manufacturers have not voluntarily withdrawn these products from the market, the FDA will take the necessary steps to withdraw them,” Morgan Liscinsky, an FDA spokesman, wrote in an e-mail.
When? “In the near future,” the agency announcement said.