Acetaminophen and Liver Failure

In my second day of medical school, back in 1973, a doctor explained to us the difference between a therapeutic dose of a medication and a lethal dose which could lead to death. A therapeutic dose is the dose which is prescribed for maximum benefit whether it’s for pain relief or fever reduction. The fatal dose is the one that will kill you.

Aspirin used to be the workhorse for pain relief and fever reduction. Produced from the willow tree, a form of aspirin has been used for 2400 years. With the aspirin available today, there’s a very wide margin between the therapeutic dose and the lethal dose.

For example, if you had a bottle with 100 aspirin tablets of 350 mg, you would normally take two for a therapeutic dose. Years ago, some people attempting suicide would take a whole bottle of aspirin. Certainly, they would be sorry for that, but they would live. Symptoms of aspirin overdoes include tremendous anxiety, headache, ringing in the ears (tinnitus), a racing heart, and nausea lasting approximately 12 hours.

Now Tylenol (acetaminophen) has largely replaced aspirin as the drug of choice for headaches, inflammation, and fever. Many users of Tylenol do not know that the margin between the therapeutic dose of Tylenol and the lethal dose is very narrow.

In Dr. Jen Gunter's article on supplements, she notes that acetaminophen is the most common cause of liver failure:

In the study at hand, acetaminophen was the most common cause of drug-related liver failure. From 1995-2003 it was the cause of 66.8% of the drug-induced liver injury that led to the need for a transplant; from 2004-2012, it was 78.4%; and from 2013-2020 it was 70.9%.

What many people don't know is that acetaminophen is blended in with many medications. For example, acetaminophen has been attached to hydrocodone with the medication Lorcet for years. Many over-the-counter (OTC) medications ending in cet contain acetaminophen. Recently, the acetaminophen dose has been decreased from 650 mg to 325 mg in the Lorcet.

This simple fact may come as a surprise to many. The problem with Lorcet isn’t the hydrocodone...it is the acetaminophen. As an opioid, hydrocodone use becomes tolerated. In other words, you may need to continue increasing the dose to achieve the same result. The acetaminophen will kill you from liver failure  long before the hydrocodone will.

Since acetaminophen is ubiquitous, (all over the place), depending upon the medications you may be taking, the actual amount of acetaminophen you are taking can easily pile up without a person recognizing that they are poisoning their livers.

According to Harvard Health, the maximum daily dose of acetaminophen for a healthy adult who weighs at least 150 pounds is 3000 mg to 4000 mg (3 to 4 g) per day. For older people in nursing homes that dose has been reduced to 2000 mg to 3000 mg, (3 g) of acetaminophen per day.

According to Wikipedia and my own observations, paracetamol (acetaminophen) has been over-prescribed for fever. In treatment for the common cold, it might relieve runny nose, but not sore throat, malaise, sneezing, or cough. In critical care, acetaminophen, decreases body temperature only .2 to .3°C. For use in sepsis, higher mortality, lower mortality, and no change in mortality have all been reported. Overall, there is no support for routine administration of antipyretic (fever reducing) drugs, including acetaminophen to hospitalized patients with fever and infection.

This is a point I want to make from my own observations. In my experience, acetaminophen simply is not very effective. First, fever reducers really don’t effectively reduce fevers and don’t prevent febrile seizures. Secondly fever reducers disguise the fever and make it a useless barometer for illness, infection and health. In other words, the fever is present to tell us that there’s most likely an active infection present. So, the fever is a wonderful barometer and it tells us loads of information that we need for diagnosing and treating patients.

Fevers are designed to help our bodies manage, treat, and resolve infection. There’s absolutely no point in disguising the fever, misdiagnosing the infection, delaying the diagnosis of infection, and making treatment more difficult, more expensive, and less effective.

Personally, I don’t take antipyretics (fever reducers) if I have a fever. When I had Covid, my temperature went up to 103.8 F but I did not take a fever reducer because I knew that the fever was there for a reason, and that my body was using the fever to recover from the Covid. I knew that when my fever broke six hours later that I was getting well, so the fever is an excellent barometer and very useful for managing infections and for getting well.

Parents, please read the instructions on OTC medications. Be careful to not mix OTC medication and prescription medications. Read the labels carefully on dosing of all medication contents to determine what is in the pills you are taking.

For years we have told mothers that taking over-the-counter (OTC) medication during pregnancy was safe. This has included the use of acetaminophen according to directions, but the use of acetaminophen in pregnancy has come under scrutiny recently. While some information indicates there is no link between taking acetaminophen in the first trimester and adverse pregnancy outcomes, there appears to be an association with increasing asthma, reproductive disorders in the offspring of mothers who use acetaminophen during pregnancy, autism spectrum disorder, and hyperactivity symptoms.

Many large studies provide strong evidence that acetaminophen causes an increased risk of neurodevelopmental disorders in children. The consensus recommendation seems to be to avoid prolonged use of acetaminophen in pregnancy and to only use it “when necessary” and in the lowest doses for the shortest amount of time. Do not take acetaminophen for more than 10 days.

Overdosing on acetaminophen is easily done. It is caused by taking more than 3 or 4 g of acetaminophen daily. A single dose should not exceed 1000 g and doses should be taken no sooner than four hours apart and no more than four doses in 24 hours.

According to the FDA, acetaminophen overdose in the United States is responsible for 56,000 emergency room visits, 26,000 hospitalizations, and 458 deaths per year during the 1990s. Unintentional acetaminophen overdose accounted for 25 percent of emergency room visits, 10 percent of hospitalizations and 25 percent of deaths. As I mentioned, above overdoses are frequently related to the combination of an opioids and acetaminophen.

Treatment of acetaminophen overdose includes removing the acetaminophen from the body and replenishing glutathione. Activated charcoal can be used to decrease the absorption of acetaminophen if the person comes to the hospital soon after an overdose. The antidote is acetylcysteine, a precursor to glutathione. Acetylcysteine helps the body regenerate enough glutathione to prevent or at least decrease the possible damage to the liver.

If you decide that you must take acetaminophen, then be aware that the range between dosage and overdosing is very narrow with this medication. Read the directions and remember to consider whatever other medications you may be taking which might include acetaminophen, including OTC medications.

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