Tylenol (Acetaminophen) Hepatotoxicity

Tylenol (acetaminophen), the most popular pain-killer in the United States, is also responsible for more cases of acute liver failure than any other drug or disease.

Tylenol Hepatotoxicity and Acute Liver Failure

Tylenol (acetaminophen) has been one of the most popular painkillers in the United States since the 1950s. In the 1980s, researchers found that it could cause hepatotoxicity (liver damage). Since then, the incidence of Tylenol hepatotoxicity has been on the rise.

Today, experts estimate that Tylenol overdoses cause about 2,000 cases of liver failure, 26,000 hospitalizations, and 450 deaths every year. Although many of these injuries are intentional suicidal injuries, about 50-60% accidentally occur in patients who are treating pain. More than 600 medications contain acetaminophen, and overdoses easily occur when patients combine multiple drugs.

Treatment of Tylenol Hepatotoxicity

Early treatment of a Tylenol overdose is essential for a good long-term prognosis. Fortunately, more than 80% of people who receive treatment for an overdose survive. Prognosis is best within the first 4 hours, because patients can have their stomach pumped and be given activated charcoal to reduce absorption of the drug.

Tylenol hepatotoxicity treatments include:

• N-acetylcysteine (NAC): NAC is an “antidote” to a Tylenol overdose that is most effective if given within 8-16 hours of an overdose. Healthcare professionals use the Rumack-Matthew nomogram to determine the appropriate dose to inactivate the toxic byproducts of a Tylenol overdose.
• Liver transplantation: The only way to improve survival for patients with acute liver failure is with an organ transplant from a donor. Unfortunately, the waiting list for livers is very long, and about 20% of people do not survive in time to receive a transplant.

Tylenol Hepatotoxicity Mechanism

The liver is responsible for metabolizing drugs into chemicals that can be safely absorbed by the body. When patients take too much Tylenol, the liver cannot safely metabolize the drug, and a toxic byproduct causes hepatotoxicity (liver damage).

When the liver metabolizes normal doses of Tylenol, about 90% is converted into chemicals that can be excreted in the urine. Most of the remaining 10% is excreted in bile, which is a digestive enzyme that helps break down food. When patients take too much Tylenol, the liver creates a toxic byproduct called N-acetyl-p-benzoquinonimine (NAPQI) that damages hepatocytes (cells in the main tissue of the liver that make up nearly 80% of its mass).

The other mechanisms of Tylenol hepatotoxicity include abnormal immune response and mitochondrial dysfunction. These mechanisms cause extensive destruction of hepatocytes, inflammation, and swelling. Damaged cells release proteins and enzymes into the bloodstream, and blood tests can help a doctor diagnose liver damage within 24 hours of an overdose.

Tylenol Hepatotoxicity Dose

In 2011, the U.S. Food and Drug Administration (FDA) issued a Safety Communication to warn that patients should not exceed 3,000-mg of acetaminophen in one day to reduce the risk of hepatotoxicity.

In 2009, the Journal of Clinical Gastroenterology published a study of Tylenol-induced hepatotoxicity. They estimated that hepatotoxicity could occur at doses of 125-150 mg/kg for a healthy adult (approximately 10-15 grams in a 24-hour period). However, the toxicity level varies depending on individual factors, and susceptible adults could be injured by less than 7 grams in one day.

Tylenol Hepatotoxicity Symptoms

There are several phases of symptoms for Tylenol hepatotoxicity. The initial phase (0-24 hrs after an overdose) usually involves severe abdominal pain on the upper-right side, nausea, vomiting, loss of appetite, feeling unwell (malaise), and sweating. During the next phase (24-48 hrs), patients may see improvement or disappearance of their symptoms, but this is when severe liver damage is occurring. Liver failure most often occurs during the third phase (48-72 hours), in which patients develop severe abdominal pain, jaundice, nausea, confusion, coma, and multi-organ system failure. Patients who survive the third phase typically see an improvement in their symptoms over the next two weeks, and more than 70% fully recover in three months.

Tylenol hepatotoxicity symptoms:

• Abdominal pain
• Loss of appetite
• Nausea, vomiting
• Lethargy or sleepiness
• Feeling unwell
• Sweating
• Jaundice (yellowing of the skin and whites of the eyes)
• Confusion
• Encephalopathy
• Behavior changes
• Coma
• Death