Tylenol (acetaminophen) is the most popular over-the-counter (OTC) pain relief medication used in the U.S. 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 Consumer Healthcare Products Association, about 52 million consumers in the U.S. use products containing Tylenol each week.
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 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.
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 safely 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.
How Tylenol Works
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.
Tylenol Forms and Doses
Tylenol is available in tablet, chewable tablet, capsule, suspension or solution (liquid), extended-release (long-acting) tablet and orally disintegrating tablet 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 4,000 mg. Taking more than 4,000 mg of Tylenol a day puts users at risk for liver failure. Experts say anyone taking Tylenol long-term for chronic pain should consider having liver function tests done once or twice a year.
Users do not need to take Tylenol with food or on a full stomach. Don’t take acetaminophen if you drink three or more alcoholic drinks a day, and don’t take more than one product that contains acetaminophen at a time.
To administer the medicine to children, use the child-specific product with a dosing cup or dropper that comes with it. Teaspoons found in the home vary in size and their use to administer Tylenol could overdose or underdose a child. You may need to shake the liquid before each use.
The Tylenol Meltaways chewable tablet softens in the mouth to make it easier to chew. Chew the tablet thoroughly before swallowing it.
Meltaways are orally disintegrating tablets. Place the tablet in your mouth and either wait for it to dissolve or chew it before swallowing.
Extended-release tablets are meant to be swallowed whole. Do not split, chew, crush or dissolve these tablets before swallowing.
Because acetaminophen is present in hundreds of medications, it’s important to read the labels of all prescription and OTC drugs to see if they contain it.
Some labels may replace the word acetaminophen with:
The FDA, National Council for Prescription Drug Programs (NCPDP) and pharmacies across the nation are working to ensure “acetaminophen” is fully spelled out on prescription labels. NCPDP estimates that more than 75 percent of pharmacies in the U.S. are part of this effort.
Complications Associated with Tylenol
Tylenol is associated with serious complications, including liver damage and rare but dangerous skin reactions. It is the leading cause of acute liver failure in the U.S., 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 U.S. In England, it is the leading cause of liver failure requiring transplants.
“Acetaminophen is a dangerous drug,” Dr. John Brems, professor of surgery and chief of intra-abdominal transplantation at Loyola University in Chicago told 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.”
Timeline of FDA Tylenol Actions
FDA issued guidelines for adding overdose information to packages.
The agency confirmed the link between Tylenol and liver damage and added a black box warning, the agency’s strongest warning, to the drug’s label.
FDA asked drug manufacturers to limit the strength of acetaminophen in prescription drug products to 325 mg.
The agency added a warning highlighting the potential for allergic reactions (e.g., swelling of the face, mouth, and throat, difficulty breathing, itching, or rash) to the label of all prescription drug products that contain acetaminophen.
FDA released a safety warning about Tylenol and skin reactions.
The agency announced its intent to take steps to withdraw approval of prescription combination drug products containing more than 325 mg of acetaminophen.
FDA announces findings from review of acetaminophen use during pregnancy.
Tylenol and 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, sulfate 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, 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.
“Use of Tylenol, particularly with alcohol, can readily cause hepatitis and liver failure.”
– Dr. Joel Weinstock
Dr. Joel Weinstock, professor and chief of the division of gastroenterology and hepatology at Tufts New England Medical Center in Boston, told ABC News. “This [liver failure] happens frequently. Some of these patients will require [a] liver transplant because the damage to the liver is so severe.”
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.
Signs of Tylenol Poisoning and Acute Liver Failure
There are four phases of Tylenol-induced poisoning and liver failure with varying symptoms. It is critical to seek help immediately because complete liver failure can occur within 72 hours of Tylenol ingestion.
Occurs in the first 24 hours after taking the drug. People usually experience nausea, vomiting, paleness (pallor) and excessive sweating (diaphoresis).
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.
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.
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)
Tylenol Liver Damage Warnings
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, the FDA’s strongest warning, for liver failure to all products containing Tylenol.
The agency is also considering other recommendations, including the following notices about:
- 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
The agency recommended removing acetaminophen from some popular pain relief drugs such as Vicodin and Percocet and decreasing the recommended maximum daily dose.
In 2013, Johnson & Johnson added a warning to the caps of bottles of Extra Strength Tylenol warning consumers that the drug contains acetaminophen and may cause liver failure. That same year, a judicial panel formed a multidistrict litigation for lawsuits against Johnson & Johnson and/or McNeil over severe liver damage.
In 2014, the FDA announced its intention to institute proceedings to withdraw approval of prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit that remain on the market.
Fatal Skin Reactions
In August 2013, the FDA released a safety warning about Tylenol and rare, dangerous skin reactions. It warned these reactions can occur with first-time use of acetaminophen or at any time while it is being used.
The FDA required a warning be added to the labels of prescription drug products containing acetaminophen to address the risk of serious skin reactions. It also requested that manufacturers add a warning about serious skin reactions to the product labels of OTC acetaminophen drug products.
In its safety alert, the FDA advised of three reactions:
- Stevens-Johnson Syndrome (SJS)
- Toxic epidermal necrolysis (TEN)
- Acute generalized exanthematous pustulosis (AGEP)
The agency said it identified 91 cases of SJS and TEN and 16 cases of AGEP from 1969 to 2012 that resulted in 67 hospitalizations and 12 deaths. 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 from these diseases may take months. The FDA advises anyone who notices these symptoms to stop taking Tylenol immediately.
Tylenol Use During Pregnancy
The FDA reviewed possible risks of acetaminophen use during pregnancy and released its findings in a January 2015 Drug Safety Communication.
According to the safety communication, two U.S. studies indicate that 60 to 70 percent of pregnant women in the U.S. reported using acetaminophen anytime during pregnancy.
One study reported an increased association between acetaminophen use in pregnancy and attention deficit hyperactivity disorder (ADHD) in children. Women reporting any acetaminophen use in pregnancy were also significantly more likely to have a child with a hyperkinetic disorder (HKD) diagnosis or a child who used ADHD medications, compared to unexposed women, according to the FDA.
“Associations for all outcomes were strongest for acetaminophen use in multiple trimesters and for more than 20 weeks during pregnancy,” the FDA noted.
The FDA said the study “had a number of methodologic limitations” and concluded “the weight of evidence is inconclusive regarding a possible connection between acetaminophen use in pregnancy and ADHD in children.”
Tylenol faced a string of recalls from 2009 to 2012. Some Tylenol products didn’t return to store shelves until 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. Then in 2012, McNeil recalled nearly 600,000 bottles of infant Tylenol for faulty dosing systems that could result in babies receiving too little or too much medicine.
|TYLENOL®, Extra Strength Caplets, 225 count||Uncharacteristic musty, moldy odor||6/28/11|
|TYLENOL® 8 Hour, TYLENOL® Arthritis Pain, and TYLENOL® upper respiratory products, and certain lots of BENADRYL®, SUDAFED PE®, and SINUTAB® products||Insufficient development during manufacturing||1/14/11|
|Tylenol Cold Multi Symptom Daytime Liquid 8 oz Citrus Burst||Mislabeled - alcohol content not listed on front panel||11/27/10|
|Tylenol 8 hour Caplets in 50 count bottles||Off odor - musty/moldy||10/18/2010|
31 Million Bottles Recalled
Johnson & Johnson recalled 31 million bottles of Tylenol after the drug was 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 issued a recall and sent warnings to hospitals and distributors. The murders remain unsolved.
Accidental Tylenol Overdose
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.
“We see unintentional overdoses when people combine multiple products with acetaminophen, such as Nyquil and Tylenol,”
-Dr. Jan Engle, past president, American Pharmacists Association, told The Chicago Tribune.
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, such as Theraflu, for example, they risk an overdose.
Intentional Tylenol Overdoses
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.
Symptoms of Tylenol Overdose
Doctors diagnose Tylenol poisoning by obtaining a history of Tylenol ingestion and doing blood tests.
Symptoms of overdose include:
- increased sweating
- loss of appetite
- nausea or vomiting
- stomach cramps or pain
- swelling, pain, or tenderness in the upper abdomen or stomach area
Treatment for Tylenol Overdose
It is critical to seek treatment immediately in the case of a 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 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.
Products Containing Tylenol
Tylenol is used in combination with other active ingredients in a number of prescription and OTC medications.
Most Common Tylenol Products:
- Tylenol Brand Products
- Extra Strength Tylenol
- Tylenol Arthritis Pain
- Tylenol Cold Multi-Symptom Severe
- Tylenol Cold & Flu Severe
- Simply Sleep
- Children’s Tylenol Meltaways Chewable Tablets
- Children’s Tylenol Plus Cold
- Children’s Tylenol Plus Cough & Sore Throat
- Regular Strength Tylenol
- Regular Strength Tylenol
- Tylenol Sinus Congestion and Pain Severe
- Tylenol Cold Multi-Symptom Daytime
- Tylenol Cold Sore Throat
- Children’s Tylenol Oral Suspension
- Tylenol Meltaways Chewable Tablets
- Children’s Tylenol Plus Cold & Cough
- Children’s Tylenol Plus Flu
- Tylenol 8 Hour Muscle Aches and Pain
- Tylenol Sinus Congestion and Pain Daytime
- Tylenol Cold Multi-Symptom Nighttime
- Tylenol PM
- Infant’s Tylenol Oral Suspension
- Children’s Tylenol Plus Multi-Symptom Cold
- Children’s Tylenol Plus Cough & Runny Nose
Over-the-Counter Brand-Name Medications with Acetaminophen:
- Alka-Seltzer Plus LiquidGels
- Formula 44
- Powders Liquiprin
- Saint Joseph
- Aspirin-Free Singlet
- TYLENOL Brand Products
Prescription Brand-Name Medications with Acetaminophen:
- Hydrocodone Bitartrate
- Tylenol with Codeine