EXPLORING THE LINK BETWEEN ACETAMINOPHEN IN OPIOIDS AND SERIOUS LIVER INJURY
EXPLORING THE LINK BETWEEN ACETAMINOPHEN IN OPIOIDS AND SERIOUS LIVER INJURY
A U . S . Food and Drug Administration ( FDA ) mandate to limit the dosage of acetaminophen in pills that combine acetaminophen and opioid medications is significantly associated with subsequent reductions in serious liver injury , researchers report in a spring 2023 edition of the medical journal JAMA . The federal mandate was announced in 2011 and implemented in 2014 . hospitalizations from 2007 to 2019 . The ALFSG is a prospective cohort of adult patients with acute liver failure from 1998 to 2019 at 32 U . S . medical centers . The NIS database included 39,606 cases of hospitalizations involving acetaminophen-opioid toxicity , and the ALFSG database had 2,631 patients hospitalized with acute liver failure , including 465 with acetaminophen-opioid toxicity .
RESEARCH & CLINICAL TRIALS
“ The FDA mandate that limits acetaminophen dosage to 325 milligrams per tablet in combination acetaminophen-opioid medications was associated with a significant and persistent decline in the yearly rate of hospitalizations and proportion per year of acute liver failure cases involving acetaminophen and opioid toxicity ,” said study leader and surgeon-scientist Jayme Locke , M . D ., MPH , director of the UAB Comprehensive Transplant Institute ( CTI ) and chief of the UAB Division of Transplantation .
Patient safety – while still providing pain relief – is the reason to combine different analgesic classes in a medication . Together , the multiple drugs should provide additive synergistic analgesia while minimizing toxicity by using lower doses of each component .
The challenge was that excessive doses of acetaminophen , also known as paracetamol , are toxic to the liver . By 2005 , one study found that 43 % of acetaminophen-induced acute liver failure cases involved combination acetaminophen-opioid medications taken as therapy . So , an FDA advisory panel in 2009 recommended prohibiting the sale of combination acetaminophen-opioid medications , though the FDA instead acted to limit the amount of acetaminophen in such medications to 325 milligrams . Before the FDA mandate , these medications contained 325- 750 milligrams of acetaminophen .
In each data source , Dr . Locke and colleagues found similar declines in the yearly rates of hospitalization and acute liver failure cases associated with acetaminophen-opioid medications after the mandate . They also compared toxicity seen from acetaminophen-opioid medications against toxicity from acetaminophen alone . In contrast to the declines from acetaminophen-opioid medications after the mandate , the rates of hospitalization and acute liver failure cases associated with acetaminophen alone – where the dosage is not constrained by the FDA – continued to rise after the combination drug mandate .
Joining Dr . Locke on the JAMA study was its first author , Babak Orandi , M . D ., Ph . D ., who is a visiting assistant professor of Surgery at the UAB Heersink School of Medicine and currently is an obesity medicine fellow at the Joan and Sanford Weill Medical College of Cornell University in New York City . The authors caution that the study shows association , not causality . The changes in hospitalizations also could have come from increased public awareness and stiffer label warnings required by the FDA as part of the mandate , or changes in prescribing patterns among clinicians . However , in Canada , changes in labeling without an accompanying limit in the acetaminophen dosage was not associated with a decline in hospitalizations .
Examining the data To examine the effect of this change , researchers in the JAMA study looked at yearly rates of hospitalization and acute liver failure cases in two independent , contemporaneous data sources : the National Inpatient Sample ( NIS ) and the Acute Liver Failure Study Group ( ALFSG ). The NIS is a large U . S . hospitalization database of more than 473 million uabmedicine . org / refertransplant 7