Evaluation of a Food and Drug Administration Mandate to Limit Acetaminophen in Prescription Combination Products.

introductionIn 2014, the US Food and Drug Administration limited the production of prescription acetaminophen-opioid combination products to 325 mg per dose unit. The goal of this mandate was to decrease the likelihood of unintentional acetaminophen hepatotoxicity. This study was designed to determine if this federal regulation has succeeded in reducing unintentional acetaminophen-induced hepatotoxicity from opioid combination products.

methodsUsing data from the National Poison Data System (NPDS), we analyzed all calls to US Poison Control Centers in the years 2013 and 2015 for acetaminophen-opioid combination product exposures. We then excluded cases that were classified as intentional and those aged 12 years and younger. We used a primary endpoint of N-acetylcysteine administration; secondary endpoints included evidence of hepatotoxicity as aspartate aminotransferase elevation, opioid antagonist administration and severity of overall medical outcome.

resultsA total of 18,259 calls between the two yearlong periods met inclusion criteria. 5.16 and 5.01% of calls resulted in N-acetylcysteine administration in 2013 and 2015, respectively. 3.63 and 4.02% received naloxone in 2013 and 2015, respectively, and 0.9% in each year developed hepatotoxicity. Rates of N-acetylcysteine administration, naloxone administration, and hepatotoxicity did not differ significantly between 2013 and 2015. Severity of medical outcome was worse in 2015 as compared to 2013 with more cases being categorized as "major effect" and fewer cases being categorized as "no effect."

conclusionsThe Food and Drug Administration limitation on acetaminophen content per dose unit in opioid combination products did not reduce the occurrence of unintentional acetaminophen-induced hepatotoxicity or N-acetylcysteine administration as reported to NPDS.