Summary of FDA’s Acetaminophen Limit Linked With Reduced Serious Liver Injury:
The US Food and Drug Administration’s (FDA) 2011 announcement to limit the dosage of acetaminophen (also known as paracetamol and the brand name Tylenol) in pills that combine acetaminophen and opioid medications has led to a significant decline in serious liver injury, according to a report in the medical journal JAMA. The federal mandate was implemented in 2014, restricting acetaminophen to 325 milligrams per opioid-acetaminophen combination pill due to the toxic nature of acetaminophen to livers at high doses. Researchers found a significant and persistent decline in the yearly rate of hospitalisations and acute liver failure cases involving acetaminophen and opioid toxicity.
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Acetaminophen is a commonly used over-the-counter pain reliever that has been associated with liver injury, especially when taken in high doses. In 2011, the United States Food and Drug Administration (FDA) announced a mandate limiting the dosage of acetaminophen in pills that combine acetaminophen and opioid medications. The aim was to prevent serious liver injury caused by these combination drugs. A study published in the medical journal JAMA has now reported that the mandate is associated with a subsequent reduction in serious liver injury.
The study was led by Jayme Locke, M.D., a surgeon-scientist at the University of Alabama at Birmingham who directs the Comprehensive Transplant Institute. The researchers examined the yearly rates of hospitalization and acute liver failure cases in two data sources: the National Inpatient Sample and the Acute Liver Failure Study Group. They found a significant and persistent decline in the yearly rate of hospitalizations and proportion per year of acute liver failure cases involving acetaminophen and opioid toxicity after the FDA mandate was implemented in 2014.
Combining different analgesic classes in a medication is done to provide additive synergistic analgesia while minimizing toxicity by using lower doses of each component. However, too-high doses of acetaminophen are toxic to the liver. One study found that 43 percent of acetaminophen-induced acute liver failure cases involved combination acetaminophen-opioid medications taken as therapy. The FDA advisory panel recommended banning the combo acetaminophen-opioid medications in 2009. Instead, the FDA acted to limit the dose of acetaminophen in those combination acetaminophen-opioid medications to 325 milligrams.
When the researchers compared the toxicity seen from acetaminophen-opioid medications versus toxicity from acetaminophen alone, they found that rates of hospitalization and acute liver failure cases associated with acetaminophen alone continued to rise after the combination drug mandate. This suggests that the FDA mandate was successful in reducing the incidence of liver injury caused by acetaminophen and opioid combination drugs.
The study’s authors caution that the findings only show association, not causality. Increased public awareness and stiffer label warnings required by the FDA as part of the mandate, or changes in clinician prescribing patterns, may have contributed to the reduction in serious liver injury. However, the results are promising and suggest that limiting the dosage of acetaminophen in opioid-acetaminophen combinations can be an effective strategy to prevent liver injury.
In conclusion, the FDA mandate limiting the dosage of acetaminophen in pills that combine acetaminophen and opioid medications has been associated with a significant and persistent decline in the yearly rate of hospitalizations and proportion per year of acute liver failure cases involving acetaminophen and opioid toxicity. This study provides important evidence that limiting the dosage of acetaminophen in combination drugs is a useful strategy to prevent serious liver injury. Patients should continue to be cautious when taking acetaminophen-containing medications and follow their healthcare provider’s advice with regard to dosage and duration of use.
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