Acetaminophen Overdose: A Greater Risk Than Autism Concerns

Social media and news feeds have been circulating unverified claims about a potential connection between acetaminophen and autism in children. However, medical experts emphasize a far more serious and well-documented concern: acetaminophen overdose, a leading cause of hospitalization and death related to non-prescription drugs in the United States.

The Scope of Acetaminophen Poisoning

Acetaminophen poisoning results in an estimated 56,000 emergency department visits annually, with approximately 2,600 hospitalizations. It is responsible for nearly half of all acute liver failure cases in the U.S. And roughly 20% of liver transplants nationwide.

Decades of Research at CU Anschutz

Kennon Heard, MD, PhD, a professor in the CU Anschutz Department of Emergency Medicine and section chief of medical toxicology, has studied acetaminophen poisoning for over 25 years. CU Anschutz and Denver Health, home to the Rocky Mountain Poison & Drug Safety Center, have been central to acetaminophen research for the past 40 years. Dr. Heard is currently leading a clinical trial investigating a latest approach to reduce liver damage in severe overdose cases.

Why Acetaminophen Overdoses Occur

Acetaminophen, the active ingredient in Tylenol and many store-brand pain relievers, is generally safe when taken as directed. Problems arise from exceeding recommended doses, either through a single large dose or repeated overdoses over time.

“There are cases where people accidentally take too much acetaminophen,” says Dr. Heard. “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 linked to suicide attempts and self-harm. The accessibility of acetaminophen in most medicine cabinets contributes to this risk.

Limitations of the Current Antidote

For decades, acetylcysteine has been the standard antidote for acetaminophen overdose, effectively preventing liver damage when administered promptly. However, its effectiveness 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,” explains Dr. Heard.

Exploring an Alternative: Fomepizole

Researchers are now investigating fomepizole, a drug approved for treating poisoning from ethylene glycol and methanol (antifreeze), as a potential treatment for acetaminophen overdose. Fomepizole blocks enzymes that convert these substances into toxic byproducts.

Interest in using fomepizole for acetaminophen overdose dates back to the 1990s, with initial evidence from case reports and animal studies. More recently, doctors have increasingly used it off-label for severe acetaminophen poisoning.

A Phase II Clinical Trial

A current phase II clinical trial, led by Dr. Heard and colleagues, aims to determine if adding fomepizole to standard acetylcysteine treatment can reduce liver damage in high-risk patients after an acetaminophen overdose. This “proof of concept” study will compare liver enzyme levels between patients receiving both medications and those receiving acetylcysteine alone.

The trial is being conducted at Denver Health, UCHealth University of Colorado Hospital, Children’s Hospital Colorado, and other sites. Researchers hope to enroll approximately 40 participants within 12 to 18 months. Positive findings could lead to larger trials examining long-term outcomes, including survival and the require for liver transplants.

A Reminder About Medication Safety

“The message that I would want to get out,” says Dr. Heard, “is that people should carefully read medication labels, avoid exceeding recommended doses, and recognize that acetaminophen may be present in multiple products at home.”

Heard notes that the number of deaths from accidental acetaminophen overdose is comparable to those from deliberate overdoses.

Study Collaborators

Dr. Heard’s collaborators on the study include Richard Dart, MD, PhD, and Andrew Monte, MD, PhD.