MAR 07, 2023 8:05 AM PST

FDA mandate decreased acetaminophen liver failure

WRITTEN BY: Amielle Moreno

In the US and many developed countries, acetaminophen is the number one cause of drug-induced acute liver failure. Seven and a half to 10 grams of acetaminophen in less than eight hours can be toxic. While dangerous as a solo treatment, there can be a significant risk of acetaminophen overdose when combined with opioids in pain pills such as hydrocodone.

Acetaminophen/opioid drugs are often prescribed by physicians to treat pain while avoiding an overdose on either one of the medications. The US Food and Drug Administration was aware in 2005 that popular and habit-forming medicines like Vicodin were implicated in 43% of acute liver failure cases. But the combo was still causing acute liver failure and hospitalization.

After careful consideration in 2009, an FDA advisory panel recommended prohibiting the sale of this troublesome med combo in hopes of eliminating the public’s risk of acute liver failure.

Instead, in 2011 the FDA decided to limit how much of the popular analgesic could be combined in opioid medications. The 750 milligram doses were reduced to 325 milligrams of acetaminophen. Now, a new study out of JAMA has the results of this public safety decision.

Large amounts of acetaminophen cause acute liver failure by overwhelming the series of enzymes responsible for breaking it down. Several liver cell enzymes metabolize acetaminophen molecules into intermediates and then endpoint metabolites. During an acetaminophen overdose, the enzymes become overwhelmed. Unfortunately, one of the intermediate metabolites is highly reactionary. It begins destroying cells when it is not broken down rapidly enough, attaching to mitochondrial proteins and killing liver cells as a result.

Antioxidant therapy can only be used to treat overdose patients for a limited timeframe. The only available therapy once this window closes is a liver transplant.

Using two safety assessment systems, a group of researchers from University of Alabama at Birmingham and Weill Cornell Medicine monitored cases of acute liver failure and hospitalizations pre and post the limitation mandate by the FDA. Reducing the dosage of acetaminophen to 325 milligrams in the acetaminophen-opioid cocktail “was associated with a significant and persistent decline in the yearly rate of hospitalization,” and acute liver failure cases, reports Dr. Jayme Locke, study leader and surgeon-scientist from the University of Alabama at Birmingham.

One of the safety systems calculated a steady increase of 11% acetaminophen-opioid toxicity hospitalizations per year until the mandate. At that point, the stat began to decline at a symmetrical rate of 11%.

The same reduction was not witnessed in Canada, where there are comparable warning labels and livers. These findings support the perspective that the mandate is having the desired effect of reducing acute liver failure via this particular public health risk.

Sources:   Redox Biology, EurekAlert!, Hepatology, FDA,  JAMA: FDA rule lowering drug dose is associated with less liver injury

About the Author
Doctorate (PhD)
Amielle Moreno earned her doctorate in neuroscience from Emory University and has dedicated her career to science communication, news coverage, and academic writing/editing. She is a published researcher who has branched out to author articles for various science websites. She recently published an original research article detailing her findings on how sensory areas of the brain respond to social sound. When she's not writing or editing, you can find her spinning the latest neuroscience news into comedy gold, hosting her podcast "Miss Behavior Journal Club." This fortnightly humorous podcast features the latest in behavioral research. Her goal in life is to defend and discover scientific truths.
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