DENVER, January 18, 2026 — While social media buzzes with unverified links between acetaminophen and autism, medical experts are urgently focused on a far more immediate and documented danger: acetaminophen overdose.
Acetaminophen Overdose: A Silent Epidemic
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Each year, tens of thousands of Americans require emergency care due to acetaminophen poisoning, highlighting a widespread, yet often overlooked, public health crisis.
- Acetaminophen poisoning sends an estimated 56,000 people to emergency departments annually.
- Approximately 2,600 people are hospitalized each year due to acetaminophen overdose.
- Acetaminophen is implicated in nearly half of all acute liver failure cases and 20% of liver transplants in the U.S.
- Researchers are testing a novel approach using a drug typically reserved for antifreeze poisoning to combat severe liver damage.
Acetaminophen poisoning is one of the leading causes of hospitalization and death related to non-prescription drugs in the United States. This sobering statistic comes from Kennon Heard, MD, PhD, a professor in the CU Anschutz Department of Emergency Medicine and section chief of medical toxicology.
The Scale of the Problem
An estimated 56,000 people visit emergency departments each year because of acetaminophen poisoning, with around 2,600 requiring hospitalization. The drug accounts for nearly half of all acute liver failure cases nationwide and roughly 20% of liver transplants.
What happens when you take too much acetaminophen? The drug, when taken in excess, can cause severe liver damage, potentially leading to failure and the need for a life-saving transplant.
Heard has dedicated over 25 years to studying acetaminophen poisoning and is currently spearheading a clinical trial exploring a new strategy to mitigate liver damage in severe overdose cases. The experimental treatment utilizes fomepizole, a medication commonly administered to individuals poisoned by antifreeze.
Heard emphasizes the longstanding role of the University of Colorado and Denver Health, home to the Rocky Mountain Poison & Drug Safety center, in this critical research. “We have been the center of the acetaminophen research universe for the past 40 years. There’s been a long history of this type of work being done here, and it’s great to be a part of it,” he says.
Why Are Overdoses Happening?
Acetaminophen, the active ingredient in Tylenol and numerous store-brand pain relievers, is widely used for mild to moderate pain and low-grade fever. It’s also a common component in over-the-counter remedies for colds, flu, sinus issues, and menstrual discomfort.
The medication has a decades-long safety record when used as directed. However, problems arise when individuals exceed recommended dosages, either through a single large dose or repeated overconsumption over time.
“There are cases where people accidentally take too much acetaminophen,” Heard explains. “Or maybe they have a really bad toothache, and they think if two is good, four is better, eight is even better, and so on. Or it’s someone who’s taking multiple repeated overdoses. Those are the people who get into trouble.”
Overdoses are also frequently associated with suicide attempts and self-harm, Heard notes. “The No. 1 rule at the Poison Center is that if it’s available, people will take it, and a lot of people have Tylenol in their medicine chest.”
The Limitations of Current Treatment
For decades, acetylcysteine has been the standard antidote for acetaminophen overdose, effectively preventing serious liver damage when administered promptly.
However, its efficacy diminishes significantly if treatment is delayed beyond eight hours after the overdose.
“The problem is that many patients don’t present with acetaminophen poisoning until after they have liver injury, at which point the acetylcysteine is less effective, and in some cases doesn’t really work at all,” Heard says.
A Novel Approach: Repurposing an Antifreeze Drug
The current clinical trial, led by Heard and his team, centers on fomepizole, a drug already approved for treating poisoning from ethylene glycol and methanol—toxic substances found in antifreeze. Accidental exposure to these substances can occur, and fomepizole is sometimes used in cases of alcohol use disorder where individuals have ingested antifreeze as a substitute for alcohol.
Fomepizole functions by blocking alcohol dehydrogenase enzymes, preventing the body from converting ethylene glycol and methanol into harmful byproducts.
Interest in utilizing fomepizole for acetaminophen overdose dates back to the 1990s, during Heard’s medical toxicology training. Initial evidence stemmed from individual patient case reports and animal studies, particularly in severe overdose scenarios.
More recently, doctors have increasingly used fomepizole “off-label” to treat serious acetaminophen poisoning.
Richard Dart, MD, PhD, a professor of emergency medicine and Heard’s longtime mentor, proposed a formal clinical trial to rigorously evaluate the drug’s potential. Dart has directed Rocky Mountain Poison & Drug Safety since 1992.
A ‘Proof of Concept’ Trial
The ongoing phase II trial aims to determine whether combining fomepizole with standard acetylcysteine treatment can reduce liver damage in high-risk patients following an acetaminophen overdose. It’s considered a “proof of concept” study to assess whether the combination demonstrates sufficient promise to warrant larger trials.
Participants are randomly assigned to receive either both medications or acetylcysteine alone. The study is double-blind, meaning neither the patients nor the researchers know which treatment each participant receives until the trial concludes.
“We’ll compare the amount of liver damage, as measured by their liver enzymes, to see whether the fomepizole provides an added protective benefit beyond the standard treatment,” Heard says.
Patient enrollment is currently underway at Denver Health, UCHealth University of Colorado Hospital, Children’s Hospital Colorado, and several other sites. Enrollment has been slower than anticipated due to the difficulty of identifying eligible patients, but researchers hope to enroll approximately 40 participants within 12 to 18 months.
Positive findings could lead to a larger trial examining long-term outcomes, including survival rates and the need for liver transplants.
A Word of Caution
“The message that I would want to get out,” Heard says, “is that people should carefully read medication labels, avoid exceeding recommended doses, and recognize that acetaminophen may be present in multiple products at home.”
“We’ve started to recognize that the number of people who die from an accidental overdose is pretty close to the number of people who deliberately take an overdose,” he says.
Heard’s collaborators on the study include Dart and Andrew Monte, MD, PhD, also a professor of emergency medicine.
