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Regulatory Focus™ > News Articles > FDA Declares Mission (Almost) Accomplished on Removal of High-Dose Acetaminophen Products

FDA Declares Mission (Almost) Accomplished on Removal of High-Dose Acetaminophen Products

Posted 27 March 2014 | By Alexander Gaffney, RAC

More than three years after initially asking all manufacturers of acetaminophen to voluntarily withdraw products containing more than 325 mg of the drug, the US Food and Drug Administration (FDA) is declaring mission (almost) accomplished.


In January 2011, FDA requested that manufacturers discontinue marketing high-dose versions of acetaminophen-defined as doses higher than 325 mg-due the drug causing severe liver failure in some patients.

"Overdose from prescription combination products containing acetaminophen account for nearly half of all cases of acetaminophen-related liver failure in the United States; many of which result in liver transplant or death," said Sandra Kweder, then in charge of FDA's Office of New Drugs, in a statement.

"The risk of liver injury primarily occurs when patients take multiple products containing acetaminophen at one time and exceed the current maximum dose of 4,000 milligrams within a 24-hour period," she added. By limiting the size of the dose, FDA officials said they hoped to cut down on the number of accidental overdoses.

In a Federal Register notice, FDA said manufacturers would have until January 2014 to stop marketing high-dose variants of the drug, after which time they would be subject to "action by FDA." The agency also proposed instituting a Boxed Warning on all acetaminophen prescription products to reflect the elevated risks of drug-induced liver injury (DILI).

Applications Removed

And in the face of that threat, nearly all manufacturers have complied with the agency.

On 26 March 2014, FDA issued two separate Federal Register notices announcing that it was officially withdrawing approval for 108 abbreviated new drug applications (ANDAs) for prescription pain medications containing more than 325 mg of acetaminophen.

"The holders of these ANDAs have voluntarily requested that approval of these applications be withdrawn and have waived their opportunity for a hearing," FDA wrote.

The majority of the 108 ANDAs were not for pure acetaminophen products, but rather combinations of acetaminophen and either hydrocodone or codeine.

In a statement, FDA noted that there are still six manufacturers who, despite no longer actively marketing their drug products, have nevertheless not "correctly withdrawn their applications" despite multiple attempts by FDA to contact the companies.

FDA's Federal Register notice indicates that those companies are: AbbVie, Ranbaxy Laboratories, Pharmaceutical Associates, Leitner Pharmaceuticals, Nesher Pharmaceuticals, and West-Ward Pharmaceutical.

FDA is in the process of petitioning to remove those applications, it said.

FDA Statement

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