Lower Dose of Acetaminophen Linked to Reduced Serious Liver Injury

In each data source, 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 versus toxicity from acetaminophen alone. In contrast to the declines from acetaminophen-opioid medications after the mandate, 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.

The detailed results looked at four groups: NIS acetaminophen-opioid toxicity, NIS acetaminophen-alone toxicity, ALFSG acetaminophen-opioid toxicity and ALFSG acetaminophen-alone toxicity. Three different time frame analyses were done for each group: 1) before and after the FDA announcement date in 2011, 2) before and after the FDA implementation date in 2014, and 3) a washout comparison of cases before the 2011 announcement date and after the 2013 implementation date.

As an example of detailed findings, 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. By Q4 2019, it was 4.4 cases per 100,000 hospitalizations. The odds of a hospitalization involving acetaminophen-opioid toxicity increased 11 percent per year before the announcement and decreased 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 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.

The authors caution that the study shows association, not causality. The changes in hospitalizations could also have come from increased public awareness and stiffer label warnings required by the FDA as part of the mandate, or changes in clinician prescribing patterns. However, in Canada, changes in labeling without an accompanying limit in the acetaminophen dosage was not associated with a decline in hospitalizations.

Source: Newswise