The Food and Drug Administration (FDA)’s 2014 mandate limiting acetaminophen (APAP) in opioid combination drugs had no effect on the incidence of unintentional APAP-induced hepatotoxicity or N-acetylcysteine administration, according to a report published in the Journal of Medical Toxicology.

In an effort to lower the risk of unintentional acetaminophen-related hepatotoxicity, the FDA had required manufacturers to limit APAP-opioid combination products to 325mg of acetaminophen per dose. Researchers from Drexel University College of Medicine, Philadelphia, PA, conducted a study to assess whether the mandate helped reduce the occurrence of unintentional hepatotoxicity from these combination products.

Using data from the National Poison Data System (NPDS), researchers analyzed calls made to U.S. Poison Control Centers between 2013–2015 for APAP-opioid combination drug exposures. Intentional cases and those occurring in individuals aged ≤12 years were excluded.

The primary endpoint was N-acetylcysteine administration and secondary endpoints included hepatotoxicity (assessed by elevated aspartate aminotransferase), opioid antagonist administration, and severity of overall medical outcome.  

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Of the total 18,259 calls during the study period, 5.16% led to N-acetylcysteine administration in 2013 and 5.01% in 2015. Naloxone was administered in 3.63% and 4.02% of cases in 2013 and 2015, respectively. Evidence of hepatotoxicity was seen in 0.9% of individuals each year. The rates of N-acetylcysteine and naloxone administration, and hepatotoxicity did not significantly differ between 2013 and 2015. Compared to 2013, severity of medical outcome was worse in 2015, with more cases being classified as “major effect”.

Overall, the findings from the study indicated no reduction in unintentional APAP-induced hepatotoxicity or N-acetylcysteine administration following the FDA’s regulation.

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