Must-read: combination acetaminophen-opioid formulations should be abandoned

January 12, 2016, 7:16 pm


The prescription paradox of acetaminophen safety. Dart RC, Green JL. Pharmacoepidemiol Drug Saf 2015 Dec 29 [Epub ahead of print]


Last week, we pointed out that the American College of Medical Toxicology (ACMT) had issued a position statement on prescribing opioids that had missed a good opportunity to call for abandoning use of pharmaceutical products that combined strong opioids such as hydrocodone with acetaminophen.

I just discovered that a recent editorial by Richard Dart and Jody Green from the Rocky Mountain Poison and Drug Center agree with my take on this matter. They point out that a review by Major et al determined that the rate of adverse events associated with acetaminophen — including fatalities and hepatotoxocity — increased from 2009 to 2012 as a proportion of drug sales. A large percentage of these adverse events are associated with exposure to combination products:

Overall, 42% of patients admitted for acetaminophen-induced ALF [acute liver failure] will identify an opioid-acetaminophen combination drug as the source of exposure.

The authors further note that there is scant evidence (translation: no real evidence that adding acetaminophen to opioids such as hydrocodone or oxycodone increases effectiveness. Since there is clear evidence that these products increase risk of hepatotoxicity, there is absolutely no rationale for using them.

The authors conclude:

The components of pioid-acetaminpohen combination drugs are readily available separately, and elimination of the combination form might well eliminate several hudred deaths per year in the USA. The toll of prescription drug abuse and liver injury clear indicates that the potential benefits of such a change outweigh the risks. Indeed, one of the FDA’s own advisory committee’s recommended this course of action in 2009.

That is the position the ACMT should have adopted.



  1. milkshake Says:

    I think the codeine/promethazine cough syrup combo has the same problem – adding promethazine does not discourage the recreational misuse, but it increases toxicity and has negligible effect on cough, and it increases drowsiness

  2. Leon Says:


    Thank you for the comment. I agree. In general I’m not a fan of combination products.