By Alan Mozes 

HealthDay Reporter

WEDNESDAY, March 8, 2023 (HealthDay Information) — Acetaminophen, a well-liked over-the-counter treatment for tens of millions fighting ache and fever, may also be present in prescription painkillers that mix acetaminophen and an opioid into one tablet.

The issue? The U.S. Meals and Drug Administration has lengthy identified that top dosages of acetaminophen (Tylenol) can hurt the liver. So, in 2011 the FDA set new security limits on precisely how a lot acetaminophen could possibly be packed into any prescription painkiller.

Now, a brand new research reveals the transfer probably saved lives.

Ever because the FDA introduced the regulatory change, which slashed the bounds on acetaminophen from as much as 750 milligrams (mg) to as much as 325 mg, there was an 11% to 16% annual drop within the variety of hospitalizations and acute liver failure circumstances involving the combo painkiller. One such combo is Vicodin, which accommodates hydrocodone and acetaminophen.

“This implies that the mandate was probably the biggest driver within the decreases in acute liver failure circumstances and hospitalizations together acetaminophen-opioid merchandise,” stated research creator Dr. Jayme Locke, director of the College of Alabama at Birmingham’s Complete Transplant Institute.

The report was printed within the March 7 difficulty of the Journal of the American Medical Affiliation. Locke and her colleagues burdened that their investigation doesn’t definitively show that the FDA mandate immediately brought about acetaminophen-opioid drug problems to plummet.

“Definitely, different components may have performed a task,” Locke famous. “For instance, the mandate might have introduced the problem of acetaminophen toxicity to the forefront for each suppliers and sufferers,” presumably main some to chop down on acetaminophen dosages on their very own.

On the similar time, she identified that the FDA mandate did not place any new limits on over-the-counter acetaminophen dosing. Not surprisingly, “comparable [downward risk] traits weren’t noticed in acetaminophen alone,” Locke stated.

In line with the research authors, the meant goal of mixing acetaminophen with an opioid was to allow docs to reveal sufferers to decrease doses of every of the 2 medicine. Given the burgeoning opioid dependancy disaster, that strategy made sense.

However researchers began to warn that at such excessive doses acetaminophen was proving poisonous to the liver.

In reality, the brand new report highlights one 2005 research that discovered greater than 4 in 10 of all acute liver failure circumstances linked to acetaminophen use ended up being traced again to acetaminophen-opioid painkillers.

In 2009, such crimson flags prompted an FDA advisory panel to advocate an outright ban on such combo medicine. Ultimately, the FDA selected the dosage restrict route.

To see if the brand new restrict had a protecting influence, Locke’s group analyzed figures compiled by the Nationwide Inpatient Pattern (NIS) and the Acute Liver Failure Research Group (ALFSG).

NIS information offered particulars on roughly 473 million hospitalizations between 2007 and 2019. ALFSG information targeted on grownup sufferers who had been handled for acute liver failure between 1998 and 2019.

The investigators then stacked pre-FDA mandate liver failure and hospitalization danger up in opposition to post-mandate danger. And what they noticed was a dramatic drop in danger, coinciding with the FDA’s 2011 mandate.

For instance, NIS information revealed that whereas roughly 12 out of 100,000 hospitalizations concerned combo drug toxicity simply earlier than the FDA transfer, that determine dropped to simply above 4 in 100,000 by 2019. And whereas the danger for being hospitalized with combo drug toxicity had been rising 11% a 12 months as much as the time of the FDA’s new restrict, that determine truly flipped to an 11% drop per 12 months after the restrict was introduced.

ALFSG figures revealed an identical dynamic: 27% of acute liver failure circumstances had been attributed to the drug combo on the time of the FDA transfer, however that determine dropped to five% by 2019.

Locke stated the research didn’t determine what proportion of combo drug customers struggled with a substance use dysfunction earlier than or after the FDA transfer. Nor did the group assess whether or not the brand new acetaminophen restrict in any approach lowered the efficiency of acetaminophen-opioid mixtures.

However primarily based on the proof, Locke stated her group is “happy with the effectiveness of the mandate at reducing acute liver failure circumstances.”

Dr. Marc Ghany, part chief of scientific hepatology analysis on the liver ailments department on the U.S. Nationwide Institute of Diabetes and Digestive and Kidney Illnesses, co-authored an editorial accompanying the research.

Ghany instructed that the FDA’s mandate can solely go thus far, provided that mixture acetaminophen-opioid formulations solely account for about 20% of complete acetaminophen use in the USA.

He identified that the research discovered “the speed of hospitalizations for people utilizing non-prescription, over-the-counter acetaminophen-only merchandise truly elevated over the identical interval.”

The problem now, stated Ghany, is what to do about toxicity danger among the many overwhelming majority of sufferers who use over-the-counter acetaminophen.

“Efforts to enhance client training on the dangers of acetaminophen damage, and to supply easy and clear data of the dangers of liver damage on the product label proceed. However this alone could also be inadequate, given the final perception amongst customers that over-the-counter medicines are protected,” he famous.

“The one option to shield in opposition to acetaminophen-related liver damage and dying,” stated Ghany, “could be to develop safer, simpler ache relievers.”

Extra data

There’s extra on acetaminophen on the U.S. Nationwide Institutes of Well being.


SOURCES: Jayme Locke, MD, MPH, director, UAB Complete Transplant Institute, chief, division of transplantation, and professor of surgical procedure, College of Alabama at Birmingham; Marc Ghany, MD, MHSc, part chief, scientific hepatology analysis part, liver ailments department, U.S. Nationwide Institute of Diabetes and Digestive and Kidney Illnesses, Nationwide Institutes of Well being, Bethesda, Md.; Journal of the American Medical Affiliation, March 7, 2023

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