Acetaminophen, Tylenol Liver Damage
- Acetaminophen, Tylenol Liver Damage
"Is it safe for me to take Tylenol?"
Tylenol is currently the most popular painkiller in the United
Americans take over 8 billion pills (tablets or capsules) of Tylenol
each year. Acetaminophen is the general (generic) name for Tylenol,
is a brand name. Although acetaminophen is contained in over 200
medications, most of them do not have the name 'Tylenol' on their
Moreover, just about every patient with liver disease in my practice
invariably asks: Is it safe for me to take Tylenol? or How much
can I take? These questions highlight the public's awareness of the
potential for acetaminophen to cause liver damage or injury.
Tylenol is a very effective pain-killing (analgesic) and
(anti-pyretic) agent. It is also a very safe drug as long as the
recommended dosage is not exceeded. In fact, the use of Tylenol
aspirin to treat fevers in infants has greatly reduced the occurrence
Reyes syndrome, an often fatal form of liver failure. Ironically,
however, taking too much Tylenol (an overdose) can also cause liver
although by a different process (mechanism), as discussed below.
Do the recommended doses of Tylenol cause any liver damage?
Some early reports did describe the occurrence of chronic liver
that was associated with the long-term use of Tylenol in the
recommended doses. These studies were published in the 1970s,
however, and I
suspect that many of these patients may have had unrecognized chronic
hepatitis C infection. Anyway, today, the consensus is that the usual
of Tylenol cause significant liver damage only rarely or not at all
people with normal livers.
Likewise, a person with liver disease does not appear to be at an
increased risk of developing additional liver injury from taking
This is so regardless of the cause of the liver disease and provided
patient does not drink alcohol regularly. Thus, Tylenol is quite safe
to use in the usual dose in patients with acute (brief duration) or
chronic (long duration) hepatitis. For example, Tylenol is routinely
prescribed to treat the flu-like symptoms that can be caused by
treatments for patients with chronic hepatitis. Keep in mind,
that all drugs, including Tylenol, should be used with caution, if at
all, in patients with severe liver disease, such as advanced
(scarring of the liver) or liver failure.
Why should we know that the generic name of Tylenol is acetaminophen?
For the remainder of this discussion, the generic name acetaminophen,
rather than to the brand name Tylenol will be used. I decided to do
to emphasize the need for people to read the labels of medicine
carefully. As mentioned above, the labels usually will say
acetaminophen rather than Tylenol. For example, each tablespoon of
nighttime cold remedy, Nyquil, contains 500 milligrams (mg) of
acetaminophen. Similarly, each tablet of Vicodin, a popular, potent
contains a narcotic, has also either 500, 650, or 750 mg of
acetaminophen, depending on the formulation.
As already mentioned, an overdose of acetaminophen can cause liver
damage. This damage occurs in a dose-related manner. (Some other
medications can cause liver injury in an unpredictable fashion that
to the dose.) In other words, liver injury from acetaminophen occurs
only when someone takes more than a certain amount of the drug.
the higher the dose, the greater is the likelihood of the damage.
is more, this liver injury from an overdose of acetaminophen is a
serious matter because the damage can be severe and result in liver
and death. In fact, acetaminophen overdose is the leading cause of
acute (rapid onset) liver failure in the U.S. and the United Kingdom.
Just how much acetaminophen is safe to take?
For the average healthy adult, the recommended maximum dose of
acetaminophen over a 24 hour period is four grams (4000 mg) or eight
extra-strength pills. (Each extra-strength pill contains 500 mg and
strength pill contains 325 mg.) A person who drinks more than two
alcoholic beverages per day, however, should not take more than two
acetaminophen over 24 hours, as discussed below. For children, the
is based on their weight and age, and explicit instructions are given
in the package insert. If these guidelines for adults and children
followed, acetaminophen is safe and carries essentially no risk of
On the other hand, a single dose of 7 to 10 grams of acetaminophen
to 20 extra-strength tablets) can cause liver injury in the average
healthy adult. Note that this amount is about twice the recommended
maximum dose for a 24 hour period. In children, a single dose of 140
(body weight) of acetaminophen can result in liver injury. Amounts of
acetaminophen, however, as low as 3 to 4 grams in a single dose or 4
grams over 24 hours have been reported to cause severe liver injury
some people, sometimes even resulting in death. It seems that certain
individuals, for example, those who regularly drink alcohol, are more
prone than others to developing acetaminophen-induced liver damage.
understand this increased susceptibility in some people, it is useful
know how acetaminophen is processed (metabolized) in the liver and
the drug causes liver injury.
How is acetaminophen processed (metabolized) in the body?
The liver is the primary site in the body where acetaminophen is
metabolized. In the liver, acetaminophen first undergoes sulphation
to a sulphate molecule) and glucuronidation (binding to a glucuronide
molecule) before being eliminated from the body by the liver. The
compound, acetaminophen, and its sulphate and glucuronide compounds
(metabolites) are themselves actually not harmful. An excessive
acetaminophen in the liver, however, can overwhelm (saturate) the
sulphation and glucuronidation pathways. When this happens, the
acetaminophen is processed through another pathway, the cytochrome
From acetaminophen, the P-450 system forms an intermediate metabolite
referred to as NAPQI, which turns out to be a toxic compound.
however, this toxic metabolite is rendered harmless (detoxified) by
another pathway, the glutathione system.
How does an overdose of acetaminophen cause liver injury?
The answer is that liver damage from acetaminophen occurs when the
glutathione pathway is overwhelmed by too much of acetaminophen's
metabolite, NAPQI. Then, this toxic compound accumulates in the liver
the damage. Furthermore, alcohol and certain medications such as
phenobarbital, phenytoin, or carbamezepine (anti-seizure medications)
isoniazid (anti-TB drug) can significantly increase the damage. They
this by making the cytochrome P-450 system in the liver more active.
increased P-450 activity, as you might expect, results in an
formation of NAPQI from the acetaminophen. Additionally, chronic
alcohol use, as well as the fasting state or poor nutrition, can each
the liver's glutathione. So, alcohol both increases the toxic
and decreases the detoxifying material. Accordingly, the bottom line
an acetaminophen overdose is that when the amount of NAPQI is too
for the available glutathione to detoxify, liver damage occurs.
Is overdose with acetaminophen usually accidental or intentional?
In the U.S., suicide attempts account for over two thirds of
acetaminophen-related liver injury, whereas accidental overdose
accounts for only
one third of the cases. In young children, accidental overdose
accounts, surprisingly, for an even lower percent of the cases. That
these often-curious toddlers, accidental overdose is responsible for
less than 10% of the instances of acetaminophen toxicity. Moreover,
vast majority of these accidental overdoses were due to unintentional
overdoses given by the caregivers of the children.
How can accidental overdose be avoided in adults?
To avoid unintentional overdoses among adults, I offer the following
Read the labels of the medication bottles carefully and determine the
amount or strength of acetaminophen in each pill or spoonful.
Become familiar with all of the other medications that you are
Remember that over 200 drugs contain acetaminophen as one of the
ingredients and that certain drugs, such as phenobarbital, can
increase liver damage.
Before you take the medication, write down (record) the maximum safe
number of pills or spoonfuls that you can ingest over 24 hours. Stick
that quantity and do not deviate. If, however, you are unsure of the
safe number of doses or think that you need to take more than you
call your doctor or pharmacist.
When you receive a prescription for a new medication, ask your doctor
or pharmacist whether it affects the body's metabolism (processing)
the other medications that you are taking, including acetaminophen.
If you have been drinking alcohol regularly, do not exceed taking 2
grams of acetaminophen over 24 hours. Be honest with yourself about
ingestion of alcohol.
Record the number of pills or spoonfuls of acetaminophen and the time
that you take them.
How can overdose be avoided in children?
The dosing of acetaminophen for children, as previously mentioned,
depends on their weight and age. To avoid overdose in children,
same procedures for them as suggested above for adults. Beyond that,
two adults should independently determine the dose of acetaminophen
child. If there is disagreement about the recommended dose, consult a
pharmacist or physician. These precautions are not excessive when you
consider that in one experimental mock situation, only 30% of adults
correctly calculated the dose of acetaminophen for their child. If a
baby-sitter is caring for a sick child, parents should carefully
the dose and schedule for the administration of the drug. The fact is
that each year, in children with high fevers who were given
doses of acetaminophen, deaths have occurred due to accidental
and the resulting liver damage.
What happens to a person with acetaminophen-induced liver damage?
Three clinical stages (phases) of acetaminophen-induced liver injury
have been described. During the first phase, that is, the initial 12
24 hours or so after ingestion, the patient experiences nausea and
vomiting. For the next perhaps 12 to 24 hours, which is the second
the so-called inactive (latent) phase, the patient feels well. In the
third phase, which begins about 48 to as late as 72 hours after the
ingestion of acetaminophen, liver blood test abnormalities begin to
Most notably, extremely high (abnormal) levels of the liver blood
tests, AST and ALT, are common with this type of liver injury. The
(prognosis) of the liver injury can be predicted fairly accurately on
the basis of the patient's clinical exam and blood tests. For
one extreme, if the patient develops severe acid buildup in the
kidney failure, bleeding disorders, or coma, then death is almost
certain. Only a liver transplant can possibly save such a patient.
What should be done if acetaminophen toxicity is suspected?
A physician should evaluate the individual immediately. Remember that
bringing the bottles of acetaminophen and all of the person's other
medications to the emergency room is always useful. The risk that an
acetaminophen overdose will cause liver injury correlates with the
level of acetaminophen relative to the time the drug was taken.
therefore, are able to estimate the patient's probability of
liver injury after an overdose. To make this determination, they
the patient's history of acetaminophen ingestion and measure the
level of the drug. With this information, the doctor then can refer
a table (nomogram) that provides an estimate of the risk of
liver injury. The accuracy of this estimate, however, depends on the
reliability of the time of ingestion and whether the acetaminophen
taken over a period of time or all at once.
With suspected acetaminophen overdose, the doctors usually will pump
(gavage) the patient's stomach to remove pill fragments. In reality,
individuals who overdose with acetaminophen in a suicide attempt will
have taken other pills in addition. Some doctors, therefore, will
consider treating the patient with activated charcoal, which binds
thereby inactivates) many medications. However, this treatment is
controversial because of a concern that the activated charcoal may
also bind the
antidote for acetaminophen overdose.
Patients who are thought to be at a high-risk or even only at a
possible risk of developing acetaminophen liver injury should be
antidote, N-acetyl cystiene (Mucomyst) orally (or intravenously in
Europe). This drug works by indirectly replenishing glutathione. The
glutathione, as you recall, detoxifies the toxic metabolite of the
acetaminophen. The N-acetyl cystiene is most effective when
administered within 12
to 16 hours after the acetaminophen was taken. Most physicians
will administer N-acetyl cystiene even if the patient is first seen
beyond this 16 hour period. Thus, a British study showed that
already with liver failure who then received the N-acetyl cystiene
more likely to survive than patients who did not receive the
Moreover, the survival occurred in these patients regardless of the
of initial administration of N-acetyl cystiene. Finally, people who
recover from acetaminophen-induced liver damage are left,
with no residual or ongoing (chronic) liver disease.
Acetaminophen (Tylenol) Liver Damage:
Acetaminophen is a very safe drug when taken as directed, even for
people with liver disease. Nevertheless, every drug carries risks.
Liver damage from acetaminophen, which can be severe, can result
from an overdose or from regular doses that are taken while drinking
Most cases of acetaminophen-induced liver injury are caused by an
intentional or suicidal overdose.
Unintentional or accidental overdose of acetaminophen can usually be
avoided with care and attention to the dosing.
Physicians can estimate a patient's probability of developing liver
injury based on the timing of the overdose and the blood level of the
In patients with acetaminophen liver damage, the usual clinical
sequence is nausea and vomiting for the first 12-24 hours, then the
seems well for the next 12-24 hours, after which abnormal liver blood
An antidote, N-acetyl cystiene, is available and should be given to
patient as soon as possible, preferably within 16 hours after the
acetaminophen was taken.
Medical Author: Tse-Ling Fong, M.D.
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