Tylenol Side Effects
Tylenol (acetaminophen) is a popular pain reliever and fever reducer found in many prescription and over-the-counter (OTC) medications. It’s generally considered safe when taken as directed. But taking large doses of the medication or combining it with alcohol can cause stomach cramps and nausea before the rapid onset of acute liver toxicity and liver failure. In rare instances, the drug can cause serious, and sometimes fatal, skin reactions.
Tylenol, also known by the generic name acetaminophen, is a prescription and over-the-counter (OTC) drug commonly used by adults and children to relieve pain and reduce fever. It’s also a common ingredient in prescription painkillers, such as Lortab and Percocet, and many over-the-counter flu and cold remedies.
When used as directed, acetaminophen is well tolerated by most people and side effects are rare.
Occasionally, the drug can cause serious side effects, including severe skin reactions and allergic reactions. Large doses of Tylenol can initially trigger stomach cramps and nausea before physical conditions quickly deteriorate, leading to liver injury, liver failure and death.
Use of the drug during pregnancy has also been called into question, but more research is needed.
High Doses Lead to Liver Damage
Liver damage is the most serious side effect of acetaminophen and it can be fatal. Liver damage can occur when a person exceeds the maximum daily dose of 4,000 milligrams — but it’s also been known to occur in some people at even lower doses.
In 2011, McNeil Consumer Healthcare, the manufacturer of Tylenol, reduced the maximum daily doses and increased the dosing interval on the labeling of some of their over-the-counter products used in older pediatric patients (usually children ≥12 years and adolescents) and adults in an attempt to protect patients from unintentional overdoses and subsequent liver damage.
For example, the maximum daily dose of Extra Strength Tylenol and Regular Strength Tylenol were decreased to 3,000 mg/day and 3,250 mg/day respectively, and the dosing interval for Extra Strength Tylenol was increased. Providers may still prescribe or recommend the 4 g adult daily maximum to patients ≥12 years of age (but are advised to use their own discretion and clinical judgment).
Several people have filed lawsuits claiming liver failure after taking a recommended dose. One reason some experts warn about the dangers of Tylenol is the fine line between the recommended dose and the dose at which the drug becomes toxic.
The maximum safe oral daily dose for children is weight-based at 75 mg/kg per day. Using that guideline, a 40-pound child could safely consume two 160 milligram Children’s Tylenol tablets up to four times in a 24-hour period.
Severe damage can be swift, occurring in as little as 24 hours — and the problem is so common that acetaminophen poisoning is the nation’s leading cause of acute liver failure. Combining the drug with alcohol can raise the risk of liver damage.
“Use of Tylenol, particularly with alcohol, can readily cause hepatitis and liver failure,” 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.”
Overdose Signs and Acute Liver Failure
The initial signs and symptoms of an overdose include diarrhea, sweating and a loss of appetite. Vomiting, stomach cramps and abdominal pain are common. Because the liver is located in the upper right quadrant of the abdomen, a person may experience pain, swelling and tenderness in that region.
There are four distinct phases of Tylenol-induced poisoning. It is critical to seek help immediately if you experience any of the following symptoms because complete liver failure can occur within 72 hours of ingesting the drug.
- Phase I
- This occurs in the first 24 hours after an overdose. People usually experience nausea, tiredness (fatigue), anorexia, 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 continue. In addition, fast heartbeat and low blood pressure may be present.
- Phase III
- This phase begins about 72 to 96 hours after ingesting the drug. Symptoms of liver failure or liver damage include jaundice, hypoglycemia (low blood sugar), bleeding (coagulopathy) and loss of brain function from toxins. Multiple organ failure and death may also occur at this stage.
- Phase IV
- Patients who survive Phase III spend this time in recovery. This phase lasts four days to three weeks. Symptoms resolve during this period.
How Acetaminophen Causes Liver Failure
The drug is primarily metabolized, or broken down, 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. Too much NAPQI causes liver damage.
While some cases of Tylenol poisoning are purposeful, many are not. Acetaminophen is a common ingredient in many medications, including a number of narcotic painkillers and flu and cold medications sold over the counter. As a result, people sometimes take far more than the maximum daily dose without even realizing it.
“We see unintentional overdoses when people combine multiple products with acetaminophen, such as Nyquil and Tylenol.”
People who drink alcohol or take certain medications, such as anti-seizure or anti-tuberculosis drugs, in combination with acetaminophen products also face a greater risk of liver damage.
It is critical to seek treatment immediately in the case of a Tylenol overdose. If an overdose is suspected and the patient seeks medical attention promptly, most doctors will pump (gastric 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 works by reducing acetaminophen absorption in the body. Studies show that it reduces absorption by as much as 30 percent. If the patient presents for treatment within one hour of taking the drug, oral activated charcoal may be given in conjunction with NAC. Charcoal slows the absorption of the drug 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.
Potentially Deadly Skin Reactions
In August 2013, the FDA released a safety warning about Tylenol and rare, dangerous skin reactions. These reactions can occur with first-time use of acetaminophen or at any time while it is being used.
- Stevens-Johnson Syndrome (SJS)
- Toxic epidermal necrolysis (TEN)
- Acute generalized exanthematous pustulosis (AGEP)
Signs and symptoms of SJS and TENS include flu-like symptoms and a red or purple rash that spreads and blisters. The mucous membranes are frequently affected. Eventually, the blisters erupt and cause the skin to detach from the body. The conditions are extremely painful and can lead to blindness and death.
AGEP is less serious. It causes small pustules to erupt usually on the trunk and in body folds and sometimes on the face. AGEP often resolves after the patient stops taking Tylenol, usually within two weeks.
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.
ADHD Link Not Proven
Some studies have raised concerns that use of acetaminophen during pregnancy may lead to the development of attention deficit hyperactivity disorder (ADHD) and other behavioral problems, but the findings are not conclusive
A 2014 study in JAMA looked at more than 64,000 children who were born in Denmark between 1996 and 2002. The study found a small increase in ADHD among the children of moms who’d used the painkiller while pregnant.
Those who were exposed to the drug in utero were 1.3 times more likely to have a hyperkinetic disorder, which is usually marked by inattention, overactivity and impulsivity during a child’s first five years.
They were 1.29 times more likely to use ADHD medications and 1.13 times as likely to exhibit ADHD behaviors by age seven. Stronger associations were noted when a woman used the drug more frequently, or in more than one trimester.
Other studies have produced similar findings. A 2017 study in the journal Pediatrics found that children were 2.2 times more likely to develop ADHD when their mother has used acetaminophen for more than 29 days during pregnancy. Interestingly, use of the drug by both mothers and fathers showed similar associations with ADHD in offspring.
While the link between paternal use of Tylenol and ADHD in children could not be explained, there are several theories for how ingestion of the drug by mother’s can impact their child.
One theory is that acetaminophen causes abnormal hormonal exposures that affect the developing fetal brain. Another suggests that acetaminophen causes oxidative stress that interferes with brain development and kills brain cells.
Thus far, the FDA says the potential connection between Tylenol use during pregnancy and ADHD is “inconclusive.”
A spokesperson for Johnson & Johnson, which makes Tylenol, told the New York Times it wasn’t aware of any causal link and said patients should discuss the risks and benefits of the drug with their physician.
According to the Cleveland Clinic, short-term use of the drug during pregnancy of less than eight days does not appear to increase risks. Cleveland Clinic obstetrician-gynecologist Dr. Salena Zanotti says the drug is still the “safest known drug” for expectant mothers with fever and pain — and that it’s riskier not to treat a fever than to take Tylenol.
Please seek the advice of a medical professional before making health care decisions.