Tylenol (acetaminophen) is the most popular over-the-counter (OTC) pain relief medication used in the United States and around the world. The drug was first sold in 1955 as Tylenol Elixer for Children, and today millions of American adults and children use the drug every week for common ailments such as head and body aches, colds and fevers. In fact, according to the U.S. Food and Drug Administration (FDA), Americans bought 28 billion doses of products containing Tylenol in 2005 alone.
Manufactured by Johnson & Johnson subsidiary McNeil Laboratories, the drug is also available in generic. It is marketed as an effective painkiller that is safer than non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin or ibuprofen, which are associated with stomach discomfort or bleeding. Pharmacies compound Tylenol into more than 600 prescription and OTC medicines, and the drug generates more than $1 billion a year for McNeil.
Tylenol is not without its serious complications. It is the leading cause of acute liver failure in the United States, and the drug in some cases led to fatalities. The active ingredient in Tylenol, acetaminophen, accounts for more than 100,000 calls to poison centers, roughly 60,000 emergency-room visits and hundreds of deaths each year in the United States. In England, it is the leading cause of liver failure requiring transplants. In 2009, the FDA issued guidelines for adding overdose guidelines to packages and in 2011, the agency confirmed the link between the drug and liver damage.
In October 2013, Johnson & Johnson will add a warning to the caps of bottles of Extra Strength Tylenol warning consumers that the drug contains acetaminophen and may cause liver failure. Severe liver damage from the drug led people to file lawsuits against Johnson & Johnson and/or McNeil. On April 1, 2013, a judge consolidated several federal lawsuits in multidistrict litigation (MDL) in the U.S. District Court for the Eastern District of Pennsylvania.
How Does Tylenol Work?
Tylenol belongs to a class of drugs called centrally acting analgesics and antipyretic agents. An analgesic relieves pain. An antipyretic reduces fevers. For more than 50 years, doctors prescribed Tylenol for both uses.
McNeil Laboratories says Tylenol works by elevating a body’s pain threshold. Researchers believe the drug’s effectiveness stems from the fact it inhibits certain parts of the brain (neurotransmitter receptors) that register pain, such as N-methyl-D-aspartate and substance P. The drug controls fever by blocking the formation and release of a fatty acid called prostaglandin E that has the ability to regulate body temperature.
Unlike other analgesics like aspirin (Bayer) and ibuprofen (Advil, Motrin), Tylenol does not treat inflammation. It is most effective for minor aches and pains but can be used safetly for long-term chronic pain such as arthritis. In fact, the American College of Rheumatology recommends Tylenol to treat arthritis, and it is especially useful in types of arthritis that are not accompanied by inflammation, like osteoarthritis.
Tylenol is available in caplets, gel caplets and liquid forms. It is also available in several dose amounts, usually from 300mg to 1000mg. People can obtain it in prescription and non-prescription strengths. The maximum indicated dose in a 24-hour period should not exceed 4,000mg.
One potential problem with Tylenol-containing medications is accidental overdose. Because these medicines are available over-the-counter, a common misconception is that they are not dangerous. For some people, even going slightly over the recommended amount can cause acute liver failure, a condition that can have deadly consequences.
Dr. Joel Weinstock, professor and chief of the division of gastroenterology and hepatology at Tufts New England Medical Center in Boston, told ABC News: “Use of Tylenol, particularly with alcohol, can readily cause hepatitis and liver failure,” he said. “This happens frequently. Some of these patients will require [a] liver transplant because the damage to the liver is so severe.”
How Does Tylenol Cause Liver Damage?
Liver damage is the most serious side effect of Tylenol and can be fatal. Overdosing on Tylenol or other acetaminophen-containing drugs leads to Tylenol poisoning, which in turn leads to liver damage and/or failure. After someone takes Tylenol, the drug is primarily metabolized (processed) in the liver. Under normal conditions, the liver eliminates acetaminophen and its byproducts, sulphate and glucuronide, without a problem.
By themselves, these compounds are not harmful. But when too much acetaminophen builds up in the liver, the pathways to eliminate these compounds can overload. When this happens, the body uses another pathway in the liver, called the cytochrome P-450 system, to remove these byproducts. P-450 processes these byproducts but creates a toxic compound called NAPQI.
Increased Risks with Alcohol, with Pregnant Women
Too much NAPQI causes liver damage. People who drink alcohol or take certain medications, such as anti-seizure or anti-tuberculosis drugs, in combination with Tylenol or other acetaminophen products are at even greater risk for liver damage that may lead to acute liver failure and death.
For women who are pregnant, toxic levels of NAPQI can also pass through the placenta. After 14 weeks, the baby’s liver is susceptible to the toxin, and it may cause fetal death if not treated immediately.
Doctors diagnose Tylenol poisoning by obtaining a history of Tylenol ingestion and doing blood tests.
Tylenol and the FDA
To reduce the risk of liver damage from Tylenol overdose, the FDA released a 2011 requirement for manufacturers of all prescription medications containing acetaminophen to limit the amount of the drug to 325mg per tablet or capsule. McNeil and other drug makers are now also required to add a black box warning for liver failure to all products containing Tylenol.
The FDA recommended the removal of acetaminophen from some popular pain relief drugs such as Vicodin and Percocet and decreasing the recommended maximum daily dose. The agency is also considering other recommendations, including the following:
- Acetaminophen narcotic combinations
- Appropriate dose for efficacy
- Package size restrictions
- Pediatric dosing
- Safe daily dose for healthy individuals
- Safe daily dose in chronic liver disease
- Safe daily dose when used with alcohol
In addition to concerns over liver toxicity, Tylenol faced a string of recalls from 2009 to 2012, and some Tylenol products only recently returned to store shelves in 2013. In 2009, McNeil recalled many Tylenol brands because a chemical for treating wood made it into the medicine, causing nausea, vomiting and diarrhea. In 2011, it expanded the recall to include several more lots of the medication.
The recall involved tens of thousands of Tylenol products and prompted Johnson & Johnson to close a manufacturing plant. Furthermore, the FDA stepped in to supervise quality control measures at three plants.
In 2012, McNeil recalled nearly 600,000 bottles of infant Tylenol for faulty dosing systems that may result in babies receiving too little or too much medicine.
The drug was also linked to several murders in 1982 called the Chicago Tylenol Murders. Several people in Chicago died after taking Extra-Strength Tylenol caplets that were laced with cyanide. McNeil was not implicated in the murders because the bottles came from different factories, and all seven deaths took place in the Chicago area, ruling out the possibility of tampering during production.
After the murders, Johnson & Johnson sent warnings to hospitals and distributors, stopped all advertising and producing Tylenol and recalled approximately 31 million bottles. The murders remain unsolved.
A number of people sued McNeil and Johnson & Johnson after suffering liver damage. One of them is Charlotte Lee Thompson, a Florida woman who filed a lawsuit against the manufacturers of Tylenol in 2012. Thompson took Tylenol as directed for a few days and was rushed to the hospital where she was diagnosed with liver failure caused by the drug. She was hospitalized for almost two weeks to recover from Tylenol poisoning.
According to the lawsuit, McNeil and John & Johnson failed to adequately warn of the risk of liver failure when taking Tylenol while not eating and that the drug was not properly tested.
In 2007, a Philadelphia judge upheld a $5 million jury verdict against Johnson & Johnson. Plaintiffs filed a lawsuit against the company after their 1-year-old died from liver failure after taking Infants’ Tylenol.
Drugwatch can help answer your questions about Tylenol liver damage, treatments and legal options. Our patient advocates are available seven days to a week to help you or your loved ones get the help you need, call us at (800) 452-0949.
Accidental and Intentional Tylenol Overdose
Tylenol overdose is more common than most people think, and anyone who takes Tylenol because of chronic pain has the greatest risk of accidental overdose. That’s because people who take OTC medications may not realize the amount of acetaminophen they are ingesting from multiple sources.
For example, people who take two extra-strength Tylenol (at 500 mg each) four times a day are already at the 4,000mg maximum recommended dose. If they take any other drugs with acetaminophen in them like Theraflu, they risk an overdose.
“Acetaminophen is a dangerous drug,” said Dr. John Brems, professor of surgery and chief of intra-abdominal transplantation at Loyola University in Chicago to ABC News. “Many of these patients took acetaminophen in addition to alcohol. I end up transplanting three to four patients per year, and two to three die before we can transplant them. It is probably the most dangerous OTC drug in this country.”
While many Tylenol overdoses are accidental, some intentional Tylenol overdoses occur. In a 2011 study published in the British Journal of Clinical Pharmacology, researchers studied 663 people hospitalized for acute liver toxicity associated with acetaminophen.
The study found that 70 percent of the patients took a single large dose and 25 percent took staggered doses that resulted in overdose. Most of those who took a single large dose admitted that they were attempting suicide, while those who took staggered doses were trying to treat pain. Roughly 30 percent of those who took the single dose and 50 percent of those who took staggered doses also used alcohol, increasing the harmful effects of the drug.
Two-thirds received treatment without a liver transplant and survived, while 25 percent died after not receiving a transplant. In addition, 15 of the patients who received a liver transplant died. Study results also revealed that those who delayed treatment or took staggered overdoses had a higher risk of death.
It is critical to seek treatment immediately in the case of a Tylenol overdose.
Treatment for Tylenol Overdose
If Tylenol overdose is suspected and the patient seeks medical attention promptly, most doctors will pump (lavage) the patient’s stomach to remove the fragments of the pills. Blood tests can assess whether liver damage exists. In these cases, an antidote called N -acetylcysteine (NAC) may be administered.
N -acetylcysteine (NAC) works by reducing the acetaminophen absorption into the body. Studies show that it reduces absorption by as much as 30 percent. If the patient presents for treatment within one hour of Tylenol ingestion, oral activated charcoal may be given in conjunction with NAC. Charcoal slows the absorption of Tylenol in the stomach.
If the antidote is administered within eight hours of ingestion, the patient has a good chance of surviving and protecting the liver from further damage. However, if a patient is unaware they overdosed, the situation becomes dire: liver failure usually occurs within two to three days of the overdose.
Patients with severe symptoms will be admitted into the hospital for monitoring. By the time the patient reaches the final stages of liver failure, the only treatment to prevent death is an immediate liver transplant.
There are four phases of Tylenol-induced poisoning and liver failure with varying symptoms. Physical symptoms may vary depending on the phase. It is critical to seek help immediately since complete liver failure can occur within 72 hours of Tylenol ingestion.
Signs of Tylenol Poisoning and Acute Liver Failure
- Phase I: Occurs in the first 24 hours after taking the drug. People usually experience nausea, vomiting, paleness (pallor) and excessive sweating (diaphoresis).
- Phase II: In the next 18 to 72 hours, patients may develop right upper quadrant abdominal pain, nausea and vomiting. In addition, irregular heart beat and high blood pressure are present.
- Phase III: This phase begins about 72 to 96 hours after ingesting Tylenol. This is the most critical phase. Patients experience nausea, vomiting, abdominal pain, tenderness over the liver. Liver failure and damage symptoms include jaundice, hypoglycemia (low blood sugar), bleeding (coagulopathy) and loss of brain function from toxins. Multiple organ failure may also occur at this stage.
- Phase IV: This phase lasts four days to three weeks. Patients who survive phase III spend this time recovering from Tylenol poisoning, and symptoms resolve in this time period.
Other signs of liver damage may include:
- Dark colored urine
- Clay colored stools
- Yellowing of the skin or eyes (jaundice)
Fatal Skin Reactions
In August 2013, the FDA released a safety warning about Tylenol and rare, dangerous skin reactions.
The FDA advised there are three reactions:
- Stevens-Johnson Syndrome (SJS)
- Toxic epidermal necrolysis (TEN)
- Acute generalized exanthematous pustulosis (AGEP)
SJS and TEN are more serious and can be fatal. AGEP often resolves after the patient stops taking Tylenol, usually within two weeks.
Symptoms of these skin conditions include:
- Flu-like symptoms
- Skin pigment changes
- Organ damage
Recovering form these diseases may take months. The FDA advises anyone who notices these symptoms to stop taking Tylenol immediately.
Products Containing Tylenol
Tylenol is used in combination with other active ingredients in a number of prescription and OTC medications. People taking of these products should pay attention to the amount of acetaminophen they are ingesting in a 24 hour period to avoid accidental overdose. Some of the most common products include:
Tylenol Brand Products
Over-the-Counter Brand-Name Medications with Acetaminophen
Prescription Brand-Name Medications with Acetaminophen