1. Home
  2. News
  3. News Archive
  4. Limits on Acetaminophen in Acetaminophen-Opioid Combination Medications Affected Causes of Acute Liver Failure

Limits on Acetaminophen in Acetaminophen-Opioid Combination Medications Affected Causes of Acute Liver Failure

Round pills and a glass of water

Researchers found that a U.S. Food and Drug Administration (FDA) mandate limiting the amount of acetaminophen in combination opioid- acetaminophen pain relievers was associated with lower rates of acetaminophen and opioid-induced liver failure, although rates of liver failure from acetaminophen alone increased. The harms stemming from the opioid addiction crisis in the United States are well recognized, but pain relievers used in combination with (or instead of) opioids can also present safety hazards. Acetaminophen (or paracetamol) is a pain reliever and fever reducer commonly available over the counter and in prescription formulations combined with opioids. However, too much acetaminophen can cause liver injury or failure, and consumers can unintentionally ingest a dangerously high dose, especially if taking multiple acetaminophen-containing medications together. Combination acetaminophen-opioid medications can provide pain relief with lower doses of the two drugs, but previous research found that these combination medications might contribute disproportionately to acetaminophen overdoses. In January 2011, the FDA mandated that by March 2014 prescription combination acetaminophen-opioid products could only contain up to 325 mg of acetaminophen, reduced from the previous maximum of 750 mg. Manufacturers were also required to add a warning about the risk of liver injury to these medications’ labels. (This mandate did not affect over- the-counter acetaminophen products.)

To study the potential effects of this change, researchers used two large independent data sources, one on hospitalizations in the United States and the other on men and women with acute liver failure. By comparing hospitalization and acute liver failure rates, scientists concluded that after the FDA mandate went into effect, there was a significant reduction in the rate of hospitalizations associated with a combination of both acetaminophen and opioids, and in the rate of acute liver failure associated with this combination of medications. However, the rate of acute liver failure attributed to acetaminophen alone increased in the same time frame. Thus, the FDA rule on limiting the acetaminophen dose in combination acetaminophen and opioid preparations correlated with a decrease in the rate of acute liver failure and hospitalization associated with these medications. More research will be required to determine if this specific reduction in acetaminophen dosages caused these changes or if they were due to other factors, such as changes in labeling, prescribing patterns, or usage of either opioids or acetaminophen alone. Overall, these results illustrate the complexities of how acetaminophen is used and of balancing pain management and drug safety in real-world situations.

Orandi BJ, McLeod MC, MacLennan PA,…Locke JE; US Acute Liver Failure Study Group. Association of FDA mandate limiting acetaminophen (paracetamol) in prescription combination opioid products and subsequent hospitalizations and acute liver failure. JAMA 329: 735-744, 2023.
Share this page
Facebook X Email WhatsApp LinkedIn Reddit Pinterest