A perspective on the epidemiology of acetaminophen exposure and toxicity in the United States

Abstract

Acetaminophen is a commonly-used analgesic in the US and, at doses of more than 4 g/day, can lead to serious hepatotoxicity. Recent FDA and CMS decisions serve to limit and monitor exposure to high-dose acetaminophen. This literature review aims to describe the exposure to and consequences of high-dose acetaminophen among chronic pain patients in the US. Each year in the US, approximately 6% of adults are prescribed acetaminophen doses of more than 4 g/day and 30,000 patients are hospitalized for acetaminophen toxicity. Up to half of acetaminophen overdoses are unintentional, largely related to opioid-acetaminophen combinations and attempts to achieve better symptom relief. Liver injury occurs in 17% of adults with unintentional acetaminophen overdose.

Keywords::

• acetaminophen
• epidemiology
• exposure
• liver failure
• opioids
• overdose
• toxicity

Financial & competing interests disclosure

Marissa Blieden and L Clark Paramore are employees of Evidera, an independent contracting firm which received funding from Purdue Pharma in support of this review. D Shah and R Ben-Joseph are employees of Purdue Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Acetaminophen can cause liver toxicity (i.e., hepatotoxicity) including serious liver failure, usually when individuals exceed the total recommended dosage of less than 4 g/day.

• When acetaminophen is taken in combination with other opioids, the average prescribed daily dose of acetaminophen in the USA is close to 4 g/day.

• Acetaminophen use is widespread with approximately 43 million adults in the USA taking some form of acetaminophen and 7.5% using the medication at least weekly.

• Exposure to high doses of acetaminophen, alone or in combination with opioids, appears common in the USA despite the known risks of toxicity.

• Although the percentage of individuals exposed to acetaminophen that ultimately experience liver toxicity is relatively low, the actual number of individuals with toxicity is noticeable, given the large number of individuals who take acetaminophen.

• A substantial proportion of acetaminophen overdoses are unintentional, and it appears that unintentional overdoses are more likely to lead to liver toxicity than intentional overdoses.

• Exposure to acetaminophen does not always have to be chronic in nature to result in liver toxicity, especially in younger patients; however, data on this issue are not conclusive.

• Future research studies need to better quantify the levels of exposure to over-the-counter acetaminophen in addition to the exposure to prescription products that include acetaminophen.

• Numerous drug policy decisions in coming years could impact the levels of exposure to acetaminophen relative to current levels and will need to be monitored.