Acetaminophen (Tylenol, Panadol, Excedrin) #8 on the Top 10 Most Dangerous Drugs List
Acetaminophen 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 more complaints of stomach discomfort or bleeding. However, because acetaminophen and products containing that drug 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 or kidney failure - conditions that can have deadly consequences.
Unfortunately, this hit all too close to home. In 2012, a good friend of mine went to the doctor for what he thought was back strain. He was prescribed Tylenol 3. When that didn’t help his pain he took regular Tylenol also. Within days he began showing signs of overdose beginning with confusion which we later realized was hepatic encephalopathy. He experienced other side effects including stomach pain and dehydration. When his wife noticed his skin color was changing she insisted he go to the ER. He went into the hospital nine days after being prescribed the drug and was moved to the Intensive Care Unit almost immediately where his condition continued to deteriorate. Three days later, he died of multiple organ failure.
Dr. Joel Weinstock, professor and chief of the division of gastroenterology and hepatology at Tufts New England Medical Center in Boston, says, “Use of Tylenol, particularly with alcohol, can readily cause hepatitis and liver failure. This happens frequently. Some of these patients will require liver transplant because the damage to the liver is so severe.”
Even when used as directed, acetaminophen can lead to liver toxicity or death and each year accounts for an astounding 100,000 calls to poison control centers, 56,000 emergency room visits, 26,000 hospitalizations, and more than 450 deaths from liver failure alone. In fact, acetaminophen causes more cases of acute liver failure than all other medications combined.
These drugs are also the cause of accidental overdose. Often, when a desired effect is not reached such as decreased pain, people may continue to take more of the drug or combine drugs not realizing the potential danger. As a nurse, I’ve seen it happen all too often and that person wind up in ICU with liver and kidney failure. The problem is that most people take this medication without consulting a pharmacist or physician because it’s sold over the counter.
If acetaminophen is combined with a drink of alcohol the damage to the liver increases by as much as 50% and can more than double the risk of kidney damage.  Overdosing on Tylenol or even taking small amounts combined with other drugs or alcohol, or other products containing acetaminophen leads to Tylenol poisoning, this in turn leads to liver damage and potential failure. According to Harrison Ndetan, associate professor for research and biostatistics at Parker University in Dallas, "People buy acetaminophen over the counter, and they also are casual alcohol users, and they don't know that there is a harmful interaction. This is a major public health problem.” 
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, or if the person already has a compromised liver or is combining drugs or using alcohol, then the possibility of taking acetaminophen and experiencing an adverse effects is even more likely. 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 compound called NAPQI which is highly toxic.
The risk of kidney damage is even higher especially in the presence of dehydration. Even when study participants had only small doses of acetaminophen, kidney disease skyrocketed on average 123 percent. 
Another problem is intentional overdose. The problem is much more common than people realize and while it is often a “cry for help” rather than a serious attempt at suicide, people who take overdoses often have permanent liver and kidney damage or may die with or without a transplant. 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 of the overdose patients 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 though not intentional, had a higher risk of death.
“Acetaminophen is a dangerous drug,” says Dr. John Brems, professor of surgery and chief of intra-abdominal transplantation at Loyola University in Chicago. “Many of my 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.”
Other side effects include:
• Rash, hives or itching
• Bloody or black, tarry stools
• bloody or cloudy urine
• unusual bleeding or bruising
• fever with or without chills (not present before treatment and not caused by the condition being treated)
• pain in the lower back and/or side (severe and/or sharp)
• pinpoint red spots on the skin
• sore throat (not present before treatment and not caused by the condition being treated)
• sores, ulcers, or white spots on the lips or in the mouth
• sudden decrease in the amount of urine
• unusual tiredness or weakness
• yellow eyes or skin (jaundice)
• organ damage
• Stevens-Johnson Syndrome (SJS)
• Toxic epidermal necrolysis (TEN)
• Acute generalized exanthematous pustulosis (AGEP)
• blistering and scarring are associated with SIS, TEN, and AGEP
Symptoms of overdose include:
• increased sweating
• loss of appetite
• dark colored urine
• clay colored stools
• nausea or vomiting
• stomach cramps or pain
• swelling, pain, or tenderness in the upper abdomen or stomach area
• Flu-like symptoms
• Skin pigment changes
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 by January 2014.  In May 2011, manufacturers of nonprescription acetaminophen products voluntarily announced that a single children's strength of liquid acetaminophen (160 mg/5 mL) will be the only concentration available; the concentrated infant drops will no longer be produced.  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 August 2013, the FDA alerted consumers of rare but serious and potentially fatal skin reactions, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), linked to acetaminophen use. Patients should be counseled for signs and symptoms of skin reactions, such as peeling, blistering, reddening, and detachment of skin, wherein they should stop any further drug use and seek medical attention immediately.
To date the FDA has not issued a black box warning for the potential of kidney damage of failure.
Pregnancy and Pediatric Complications
Acetaminophen also has potential teratogenic effects. In a long term study published in JAMA (Feb 2014)  findings link acetaminophen use during pregnancy to increased incidence of ADHD. When taken in the last trimester the probability of the child developing ADHD severe enough to require medication was about 28%. The probability increased to 63% when his or her mother took acetaminophen during the last two trimesters of pregnancy. These are significant findings and are based on more than 64,000 Danish mothers and their children.
Researchers gathered details on pregnant subjects’ acetaminophen use long before problems in their children’s learning or behavior would have become evident, allowing the study authors to avoid a problem called “recall bias.” The research was designed to avoid many of the pitfalls of studies that find an association between an environmental exposure and the appearance of a specific outcome many years later.
Researchers tracked the study’s pediatric subjects from their first trimester in utero for as long as 15 years. In addition to surveying parents about their children’s strengths and weaknesses, the study’s authors used comprehensive and reliable databases – Denmark’s registries of physician diagnoses and of dispensed pharmacy prescriptions – to glean an accurate measure of ADHD in the population. In fact, an editorial published alongside the study praised its “notable methodological strengths”.
Tylenol, which is manufactured by Johnson & Johnson subsidiary McNeil Laboratories, generates more than $1 billion a year for McNeil.
4. Harrison Ndetan, associate professor for research and biostatistics, Parker University, Dallas; Martin Zand, M.D., professor of medicine and medical humanities, and medical director, kidney and pancreas transplant programs, University of Rochester Medical Center, Rochester, N.Y.; abstract, American Public Health Association, annual meeting, Boston, Nov. 4, 2013