Key points:
- A mandate limiting acetaminophen in drug combinations with opioids appears effective.
- A new study associates the mandate to significant reductions in serious liver injury in the years since implementation.
- The percentage of acute liver failure cases involving acetaminophen-opioid toxicity decreased 16 percent a year after the announcement.
A 2014 FDA mandate to limit the dosage of acetaminophen in pills that combine acetaminophen and opioid medications appears effective as a new study shows significant reductions in serious liver injury in the years after the mandate was implemented.
In 2005, a study found that 43 percent of acetaminophen-induced acute liver failure cases involved combination acetaminophen-opioid medications. So, in 2009, an FDA advisory panel recommended prohibiting the sale of the combination acetaminophen-opioid medications, though the FDA instead acted to limit the dose of acetaminophen in those combination acetaminophen-opioid medications to 325 milligrams. Before the FDA mandate, such medications contained 325 to 750 milligrams of acetaminophen.
To examine the effect of this change, investigators at the University of Alabama and Weill Cornell Medicine looked at yearly rates of hospitalization and acute liver failure cases in two independent data sources: the National Inpatient Sample (NIS), and the Acute Liver Failure Study Group (ALFSG). The NIS is a very large U.S. hospitalization database with more than 473 million hospitalizations from 2007 to 2019. The ALFSG is a prospective, 32 U.S. medical center cohort of adult patients with acute liver failure from 1998 to 2019.
In the NIS group, the predicted incidence of hospitalizations associated with acetaminophen-opioid toxicity one day prior to the FDA announcement was 12.2 cases per 100,000 hospitalizations. According to the study findings, published in JAMA, by Q4 2019, that number decreased to 4.4 cases per 100,000 hospitalizations. The odds of a hospitalization involving acetaminophen-opioid toxicity increased 11 percent per year before the announcement, while decreasing 11 percent per year after the announcement.
In the ALFSG group, the predicted percentage of acute liver failure cases from acetaminophen-opioid toxicity one day prior to the FDA announcement was 27.4 percent. By Q3 2019, it was 5.3 percent. The percentage of acute liver failure cases involving acetaminophen-opioid toxicity increased 7 percent per year before the announcement, and decreased 16 percent a year after the announcement.
The authors caution that the study shows association, not causality. Still, the positive decrease in toxicity cases since the mandate is significant.
Information provided by Weill Cornell.