By Alan Mozes
WEDNESDAY, March 8, 2023 (HealthDay Information) — Acetaminophen, a preferred over-the-counter medicine for thousands and thousands fighting ache and fever, will 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 recognized 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 possible 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 possible the biggest driver within the decreases in acute liver failure circumstances and hospitalizations together acetaminophen-opioid merchandise,” mentioned research writer Dr. Jayme Locke, director of the College of Alabama at Birmingham’s Complete Transplant Institute.
The report was revealed within the March 7 subject of the Journal of the American Medical Affiliation. Locke and her colleagues burdened that their investigation doesn’t definitively show that the FDA mandate straight brought about acetaminophen-opioid drug problems to plummet.
“Definitely, different components might have performed a task,” Locke famous. “For instance, the mandate might have introduced the difficulty 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 identical time, she identified that the FDA mandate did not place any new limits on over-the-counter acetaminophen dosing. Not surprisingly, “comparable [downward risk] tendencies weren’t noticed in acetaminophen alone,” Locke mentioned.
In line with the research authors, the meant objective of mixing acetaminophen with an opioid was to allow docs to reveal sufferers to decrease doses of every of the 2 medication. Given the burgeoning opioid habit disaster, that method made sense.
However researchers began to warn that at such excessive doses acetaminophen was proving poisonous to the liver.
In truth, 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 suggest an outright ban on such combo medication. In the long run, the FDA selected the dosage restrict route.
To see if the brand new restrict had a protecting impression, Locke’s staff analyzed figures compiled by the Nationwide Inpatient Pattern (NIS) and the Acute Liver Failure Examine Group (ALFSG).
NIS knowledge supplied particulars on roughly 473 million hospitalizations between 2007 and 2019. ALFSG knowledge targeted on grownup sufferers who have 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 knowledge revealed that whereas roughly 12 out of 100,000 hospitalizations concerned combo drug toxicity simply earlier than the FDA transfer, that determine dropped to only above 4 in 100,000 by 2019. And whereas the danger for being hospitalized with combo drug toxicity had been growing 11% a yr as much as the time of the FDA’s new restrict, that determine really flipped to an 11% drop per yr after the restrict was introduced.
ALFSG figures revealed the same dynamic: 27% of acute liver failure circumstances have been attributed to the drug combo on the time of the FDA transfer, however that determine dropped to five% by 2019.
Locke mentioned 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 staff assess whether or not the brand new acetaminophen restrict in any approach diminished the efficiency of acetaminophen-opioid combos.
However primarily based on the proof, Locke mentioned her staff is “happy with the effectiveness of the mandate at reducing acute liver failure circumstances.”
Dr. Marc Ghany, part chief of medical 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 advised that the FDA’s mandate can solely go to this point, provided that mixture acetaminophen-opioid formulations solely account for about 20% of whole 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 really elevated over the identical interval.”
The problem now, mentioned Ghany, is what to do about toxicity danger among the many overwhelming majority of sufferers who use over-the-counter acetaminophen.
“Efforts to enhance shopper training on the dangers of acetaminophen damage, and to supply easy and clear info of the dangers of liver damage on the product label proceed. However this alone could also be inadequate, given the final perception amongst shoppers that over-the-counter drugs are protected,” he famous.
“The one approach to defend in opposition to acetaminophen-related liver damage and dying,” mentioned Ghany, “can be to develop safer, simpler ache relievers.”
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, medical 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