Ever year, thousands of people who unintentionally overdose on Tylenol (acetaminophen) require hospitalization and treatment for acute liver failure. Unfortunately, the incidence of Tylenol hepatotoxicity is on the rise — more than 600 medications contain acetaminophen, and many people accidentally overdose when they combine more than one of these drugs. Drug-makers are now facing a growing litigation from people who allege that they were not adequately warned about the risk.
Tylenol Hepatotoxicity and Acute Liver Failure
Tylenol (acetaminophen) is the most popular painkilling medication in the United States. Normal doses of Tylenol cause very few side effects. However, overdoses cause more cases of acute liver failure than any other drug or disease — and the incidence is rising.
Every year, thousands of people accidentally overdose and cause hepatotoxicity (liver damage). Tylenol is responsible for an estimated 26,000 hospitalizations, 450 deaths, and 2,000 liver transplants. About 50-60% of these overdoses are unintentional. They usually occur in patients who accidentally take more than one medication containing acetaminophen.
Treatment of Tylenol Hepatotoxicity
More than 80% of people who receive treatment for a Tylenol overdose survive. The earlier treatment is received, the better the long-term prognosis. If treatment is received within 4 hours of an overdose, most patients can avoid severe liver damage by having their stomach pumped (called a “gastric lavage”). Administering activated charcoal can also inactivate any Tylenol remaining in the gastrointestinal system and reduce the absorption of the drug.
Tylenol hepatotoxicity treatments include:
- N-acetylcysteine (NAC): If given within 8-16 hours after an overdose, NAC is an effective “antidote” that can prevent liver failure by inactivating the toxic byproducts of a Tylenol overdose. Determining when to administer NAC is measured by the Rumack-Matthew nomogram.
- Liver transplantation: For patients with acute liver failure, transplanting a healthy donor liver is the only way to improve survival rates. Unfortunately, about one-fifth of people on the waiting list for livers do not survive long enough to get a transplant.
Tylenol Hepatotoxicity Mechanism
Hepatotoxicity (liver damage) occurs when the liver is incapable of safely metabolizing Tylenol and creates a toxic byproduct that causes severe damage to hepatocytes (cells in the main tissue of the liver that make up 70-80% of the mass of the organ).
Normally, the liver safely metabolizes 90% of Tylenol into chemicals that can be excreted by the kidneys in urine. Most of the other 10% is metabolized into chemicals that are excreted in bile (a digestive enzyme). However, in patients who take too much Tylenol, the liver creates a toxic chemical called N-acetyl-p-benzoquinonimine (NAPQI), which causes severe damage to cell membranes.
Researchers have found that other mechanisms of Tylenol hepatotoxicity include abnormal immune responses and mitochondrial dysfunction. These mechanisms cause inflammation and swelling. They also destroy cell membranes, causing hepatocytes to release proteins into the liver and bloodstream. When doctors diagnose hepatotoxicity, they use blood tests to check for elevated levels of these proteins.
Tylenol Hepatotoxicity Dose
Researchers who published this study in the Journal of Clinical Gastroenterology in 2009 estimated that Tylenol hepatotoxicity could occur at doses between 125-mg and 150-mg / kg for a normal healthy adult, or about 10 – 15 grams in one day. However, other experts warn that less than 7 grams in one day could be harmful for some adults, and lower doses could cause toxicity in children.
The U.S. Food and Drug Administration (FDA) warns that toxicity can occur any time the recommended daily dose is exceeded. In 2011, they issued a Safety Communication to lower this recommended dose from 4,000-mg to 3,000-mg per day.
Tylenol Hepatotoxicity Symptoms
The symptoms of a Tylenol overdose typically involve severe abdominal pain (upper-right side), nausea, and vomiting. However, symptoms vary depending on the time since the overdose occurred. In Phase I (0-24 hrs), symptoms include nausea, vomiting, abdominal pain, loss of appetite, malaise (feeling unwell), and sweating. In Phase II (24-48 hrs), the patient may feel better, but severe liver damage is occurring. In Phase III (48-72 hrs), severe liver damage causes abdominal pain, jaundice, nausea, vomiting, cognitive problems, coma, and even death. Patients who receive treatment typically recover in Phase IV (4 -14 days), and more than 70% recover completely in 3 months.
Tylenol hepatotoxicity symptoms:
- Abdominal pain
- Loss of appetite
- Nausea, vomiting
- Lethargy or sleepiness
- Feeling unwell
- Jaundice (yellowing of the skin and whites of the eyes)
- Behavior changes