If Acetaminophen Is Killing People, Why Should You Trust Tylenol?

Acetaminophen is considered one of the safest pain relievers in the pharmacy. In fact most people probably think it is one of the safest drugs in the pharmacy. That’s partially because Tylenol is a household brand that most people take for granted. Unlike other over-the-counter pain relievers, it is not supposed to cause digestive upset. We suspect that if you asked 1,000 health care professionals if acetaminophen is safe for older people with kidney disease or a susceptibility to stomach upset, the vast majority would say yes! A recent study suggests that could be a mistake (Arthritis Care & Research, Nov. 24, 2024).

Should We Trust Tylenol?

“Trust Tylenol” is a phrase that has been around for decades. During the 1980s, the manufacturer launched a campaign with a refrain that went something like:

“Tylenol is the pain reliever hospitals use most. I can’t think of a better reason to trust Tylenol.”

Another old slogan:

“Trust TYLENOL. Hospitals do.”

Several years ago Johnson & Johnson launched new ads. The key phrase:

“Tylenol has been the #1 doctor recommended brand of pain reliever for over 20 years.”

Consumers assume its super safe and they also figure the dose is not that big a deal. Overdosing on acetaminophen is a lot easier than you might think. At high doses, acetaminophen can cause liver toxicity.

Stomach Ulcers Are Scary!

Stomach ulcers are a common problem. According to the CDC, nearly 15 million Americans are diagnosed with peptic ulcer disease annually. They can be a lot more dangerous than a bellyache.

The worst case is a perforated ulcer. That’s when a hole develops in the lining of the stomach. If stomach contents leak out into the abdominal cavity, they could cause life-threatening infection. This in turn can lead to sepsis and shock.

Stomach ulcers can be hard to diagnose. That’s because they can be experienced as a dull ache that comes and goes. Some people sense a peptic ulcer as severe heartburn or a gnawing sensation. Others describe it as a full feeling that persists long after a meal.

According to the National Institute of Diabetes and Digestive and Kidney Diseases:

“The most common causes of peptic ulcers are Helicobacter pylori (H. pylori) infection and nonsteroidal anti-inflammatory drugs (NSAIDs). Other causes of peptic ulcers are uncommon or rare.”

The same NIH experts add “Less common causes of peptic ulcers include:

• medicines that increase the risk of developing ulcers, including corticosteroids, medicines used to treat low bone mass, and some antidepressants, especially when you take these medicines with NSAIDs”

Acetaminophen is not included in this list!

The most recent analysis from a UK database concludes (Arthritis Care & Research, Nov. 24, 2024):

“In this large study of 180,483 acetaminophen exposed participants and 402,478 unexposed participants aged 65 years and older in the UK primary care population, we found that acetaminophen exposure was associated with an increased incidence of PUB [perforation or ulceration or bleeding], uncomplicated peptic ulcers, lower GI bleed, heart failure, hypertension, and chronic renal failure. A dose-response relationship was observed for PUB, uncomplicated peptic ulcers, and chronic renal failure.”

As a pharmacologist, I am especially impressed by “dose-response relationships.” That’s because my professors in the Department of Pharmacology at the University of Michigan impressed upon me the importance of this kind of dose response curve.

Some Simple Dose Response Curve Examples:

If 1 aspirin pill causes indigestion in 5% of subjects and 2 aspirin pills cause indigestion in 10% of subjects and 5 aspirin pills cause indigestion in 35% of subjects and 10 aspirin pills cause indigestion in 85% of subjects…then you can be reasonably certain that aspirin causes indigestion.

Still confused? The same kind of curve could be created for alcohol and response times. If one shot of vodka slows your response time by 1 second, and 3 shots slow your response time by 4 seconds and 10 shots slow your response time by 9 seconds…you could conclude that alcohol slows response times.

(I made up the data described above…but you understand the concept a tad better, right?)

If a study suggests that:

“…A dose-response relationship was observed for PUB [perforation or ulceration or bleeding], uncomplicated peptic ulcers, and chronic renal failure”

I am more likely to believe this is a true effect of acetaminophen.

NSAIDs and Stomach Ulcers:

A few years ago, we heard from a reader who developed an ulcer:

“I had to be hospitalized and receive four units of blood because of a GI bleed. The doctors at the hospital thought it was from taking a baby aspirin every day for ten years. I was following orders from my primary care physician.”

These days, doctors are more careful about routinely recommending aspirin for heart attack prevention. But they often prescribe NSAIDs for pain relief, especially now that both physicians and patients are worried about opioids.

Approximately 25 million people fill prescriptions annually for medications such as celecoxib, diclofenac, ibuprofen, meloxicam and naproxen. That doesn’t include over-the-counter pain relievers, including Advil, Aleve, Motrin IB and house brands.

This reader describes how one pill turned into more as his pain worsened:

“I’ve taken naproxen for almost 20 years for back pain. Initially, it was just one pill a day for short flare-ups that occurred a few times a year. The drug was immensely effective, much better than everything else I tried. I didn’t notice any adverse effects.

“As I’ve aged, my back condition has deteriorated, so I’ve taken more and more naproxen. Recently, I developed ulcers. My doctors tell me to stop naproxen altogether. But I’m not convinced it’s responsible for the ulcers. What’s more, I am desperate for pain relief. Do you have any ideas?”

NSAIDs such as naproxen are notorious for triggering stomach ulcers. Such drugs are responsible for at least one third of peptic ulcer disease (JAMA, Dec. 3, 2024), so we would trust your doctors on this.

H. pylori infection is also an important cause of peptic ulcer. You should ask your doctor to test for these bacteria and treat the infection if it is present. Successful treatment reduces the risk of ulcer recurrence.

Topical NSAIDs like Voltaren gel might be safer for your stomach than pills. They might still pose a risk, though, so you should check with your doctor first.

Acetaminophen (APAP) vs. Other Pain Relievers:

Many people are cavalier about APAP. It seems so much safer than other pain relievers, especially NSAIDs. In addition to heartburn and ulcers, drugs like ibuprofen or naproxen can also raise blood pressure. And that’s just for starters. Here is a link to our article on the dangers of NSAIDs.

Opioids pose an addiction risk for some people. But there are concerns about acetaminophen too, especially if the recommended dose is exceeded. When that happens, acetaminophen is dangerous. How would you know if you are overdosing on APAP? This reader demonstrates how easy it is:

Overdosing on acetaminophen is easy:

“When my husband asks me to buy him acetaminophen at the store, most of the selection is usually extra-strength. It’s harder to find any that’s not extra-strength. But regardless of the dose, he takes two before he sleeps.

“One extra-strength tablet is not the same dosage as two regulars, so having only extra-strength on hand means someone will have to take either less or more than the equivalent of two regular strength.

“After an in-office procedure, my dermatologist recommended that I take ‘a couple of Tylenol’ when I got home to prevent pain. I don’t usually take pain meds, but when I got home, I took a couple of extra-strength acetaminophen because that is what we had on hand. Then I looked at the written instructions from the physician, which specified regular strength.

“You might do people a service by warning them to watch the dosage on this product. Perhaps physicians should also emphasize what dosage they’re recommending.”

Good Advice from a Reader!

This reader is wise. People often think they know everything they need to know about acetaminophen (whether Tylenol or house brand). The difference between a regular-strength tablet (325 mg) and an extra strength one (500 mg) is significant, particularly if one is taking it several times a day.

A study from Canada describes the problem (CMAJ, April 19, 2022):

“Acetaminophen is used by millions of people worldwide. Although generally safe at therapeutic doses, acetaminophen overdose is the leading cause of acute liver failure in several countries, including Australia, the United Kingdom and the United States, where it represents 50% of all reported cases…accidental overdoses represent a substantial and increasing proportion of these events…Factors contributing to unintentional overdose include a lack of consumer awareness regarding the presence of acetaminophen in nonanalgesic over-the-counter products, unclear dosing instructions on product labels and the simultaneous ingestion of prescription and nonprescription medications containing acetaminophen.”

Canada Tried to Prevent Acetaminophen (APAP) Overdosing:

Canadian regulators changed the labeling of this drug in October 2009 and again in September 2016. The goal was to clarify the risks of overdose and make it easier to use the product safely.

Canadian researchers evaluated hospital admissions related to acetaminophen toxicity between 2014 and 2020. They were checking whether the labeling changes reduced accidental overdose of this pain reliever.

Unfortunately, the rates of hospitalization for accidental acetaminophen poisoning were unchanged between 2004 and 2020. The authors suggest that since labeling does not seem to have made any difference, regulators might want to take stronger steps such as limiting the unit dose to no more than 325 mg of acetaminophen per pill or requiring a prescription for some APAP products.

Ouch! You Read That Right…APAP by Prescription?

We can hear the howls already. People in the US do not want any restrictions on their use of OTC meds. If anything, they want more meds available without prescriptions. When powerful prescription drugs like NSAIDs or PPIs become available over the counter, consumers have an awesome responsibility to become informed. Sadly, though, they often assume such drugs are super safe. Many people never bother to read the labels.

Here is what the Canadian researchers point out about OTC drug labels:

“Because of the human and economic burden imparted by accidental acetaminophen overdoses, additional measures for preventing these episodes are required, beyond those that attempt to inform consumers about the potential risks of acetaminophen through product labels and package inserts. This is especially important when considered in light of previous research that showed that fewer than 50% of patients regularly read labelled instructions for use of over-the-counter analgesics, and only 26% read the active ingredients before first use.”

Acetaminophen is dangerous in high doses. The authors conclude:

“In light of our findings and of the limitations of product labels, implementation and evaluation of measures addressing conditions that predispose people to unintentionally ingest more than the recommended amount of acetaminophen should be considered. Examples of such measures include removing acetaminophen from nonanalgesic over-the-counter products, discontinuing opioid–acetaminophen combination products and restricting products to a maximum of 325 mg of acetaminophen per unit dose.”

Mixing and Matching with APAP Is Risky!

Many people take a variety of OTC medicines. They may not realize that a cold, flu or allergy medicine could also contain APAP. Here are just a few familiar brands that contain acetaminophen:

• Alka-Seltzer Plus Cold & Flu Liquid Gels
• Benadryl Allergy & Cold
• Coricidin HBP Maximum Strength
• Dayquil VapoCOOL Severe Cough, Cold and Flu
• Excedrin Migraine
• Robitussin Maximum Strength Severe Cough Plus Sore Throat

Changing the APAP Dose:

In 2015, the Food and Drug Administration issued regulations limiting the amount of acetaminophen in prescription combination pain pills to 325 mg per pill. According to the agency, the maximum daily dose should be 4,000 mg. Some experts believe even that is too generous and think it should be dropped to 3,250 per day.

The Old Tylenol Dose vs the New Tylenol Dose:

This reader is overdosing on Tylenol:

“I take six to eight Tylenol Extra Strength tablets a day plus one Tylenol PM at night. Will there be any side effects from this?”

A. Each Tylenol Extra Strength pill contains 500 mg of acetaminophen. Tylenol PM also has 500 mg of acetaminophen. Together, you could be swallowing as much as 4,500 mg of acetaminophen daily. That’s too much!

The makers of Tylenol Extra Strength once said that the maximum daily dose of acetaminophen is 4 grams (4,000 mg or eight extra-strength tablets). That has changed. We wonder how many people realize that there are different upper limits.

Now, the makers of Tylenol state:

“To help encourage the safe use of acetaminophen, the makers of TYLENOL have lowered the maximum daily dose for single-ingredient Extra Strength TYLENOL (acetaminophen) products sold in the U.S. from 8 pills per day (4,000 mg) to 6 pills per day (3,000 mg). The dosing interval has also changed from 2 pills every 4 – 6 hours to 2 pills every 6 hours.”

This reader is exceeding the maximum recommended daily dose of acetaminophen. Instead of consuming no more than 3,000 mg of acetaminophen she is taking in as much as 4,500 mg. Acetaminophen could potentially pose a problem at that dose. She has been doing this for some time. Too much acetaminophen is hard on both kidney and liver. She should have her doctor check both liver and kidney function.

How Does Acetaminophen Affect the Liver?

Americans, unlike the French, don’t worry very much about their livers until something bad happens. Sadly, something very bad can happen if people take too much acetaminophen. And it doesn’t take very much more than the recommended dose to get into trouble.

Here’s what ProPublica revealed over a decade ago:

“The FDA has repeatedly deferred decisions on consumer protections even when they were endorsed by the agency’s own advisory committees, records show.

In 1977, an expert panel convened by the FDA issued urgently worded advice, saying it was ‘obligatory’ to put a warning on the drug’s label that it could cause ‘severe liver damage.’ After much debate, the FDA added the warning 32 years later. The panel’s recommendation was part of a broader review to set safety rules for acetaminophen, which is still not finished.

Four years ago, another FDA panel backed a sweeping new set of proposals to bolster the safety of over-the-counter acetaminophen. The agency hasn’t implemented them. Just last month, the FDA blew through another deadline.”

How Does Acetaminophen Affect the Kidneys?

As described above, acetaminophen may be harder on the stomachs of older people than most health professionals appreciate.

The authors of this study point out that:

“The findings of our study are consistent with previous observational studies that have reported an association between acetaminophen intake and the risk of GI complications and hypertension. According to an experimental study, acetaminophen exerts an inhibitory effect on peripheral COX enzymes, suggesting that it could be a possible mechanism for the GI bleeding associated with its prescription. Furthermore, the significant dose-response relationship of an increased risk associated with acetaminophen exposure and PUB, uncomplicated ulcer, and chronic kidney disease according to the number of prescriptions also aligns with previous observational studies.^“

The idea that acetaminophen could be hard on the kidneys will also come as a surprise to many health professionals. The FDA has not highlighted this problem either. We have not seen warnings about stomach ulcers or kidney damage on the label of OTC pain relievers containing acetaminophen.

Do the makers of APAP pain relievers know that there is a risk of PUB [perforation or ulceration or bleeding] or chronic kidney failure? Do the makers of APAP pain relievers know that the OTC pain reliever phenacetin was removed from the market because of a fear of kidney damage? Specifically, do the makers of APAP pain relievers realize that acetaminophen is the “major metabolite of phenacetin?”

Drug companies cannot be sued if they list all the side effects of a given medication. We suspect that is one reason why pharmaceutical manufacturers are more than happy to list dozens of adverse drug reactions in the official prescribing information and include the nastiest ones in television commercials. But if a drug company knows about serious adverse reactions and does not warn the public, that could pose a serious legal complication.

Other APAP Side Effects:

Some people react to acetaminophen with potentially dangerous skin rashes, such as Stevens-Johnson syndrome or toxic epidermal necrolysis. These are truly horrible complications that may require hospitalization. You can read about the FDA-issued warning here.

Acetaminophen at high doses can also affect hearing.

Here is a sobering story from a reader:

“I’m an RN. A few years ago, I had a partial meniscectomy (knee surgery) and needed something for pain. I can’t take NSAIDs, so I was left with acetaminophen.

“For eight months, I took the recommended dose. I kept telling the doctor that I was concerned about taking so much acetaminophen. He said repeatedly that it wouldn’t hurt me.

“Then I noticed my hearing was deteriorating. Even as a nurse, I had no idea this could happen, but it is a known side effect.

“I stopped taking acetaminophen. Now I use heat, cold and TENS for pain. My hearing got better after I quit taking it, but that was a wake-up call.”

The Safety of OTC Drugs:

Part of the problem is that Americans view over-the-counter drugs as super safe. To some extent, that may be a result of successful advertising campaigns like the “Trust Tylenol” message.

There also seems to be an assumption that if the FDA deems a drug safe enough to be purchased OTC in supermarkets, convenience stores, airports and pharmacies, then it must be virtually without risk. Sadly, the agency has been incredibly slow to educate the public adequately about the risks of acetaminophen toxicity.

People often don’t read labels, and even if they do, they may ignore the warning to only take a pain reliever like acetaminophen at the recommended dose or for no more than 10 days without medical supervision. Various studies and surveys have shown that as many as one-fourth of Americans routinely take higher OTC pain reliever doses than recommended on the label. And that is the crux of the problem with acetaminophen. Our reader who was taking as many as eight Tylenol Extra Strength tablets plus a Tylenol PM at night was overdosing.

How Much Tylenol Is Too Much?

Just a little more than the maximum recommended dose of 4 grams (eight extra-strength Tylenol tablets) can trigger liver toxicity in some people.

Here again is ProPublica:

“Taken over several days, as little as 25 percent above the maximum daily dose – or just two additional extra strength pills a day – has been reported to cause liver damage, according to the agency. Taken all at once, a little less than four times the maximum daily dose can cause death. A comparable figure doesn’t exist for ibuprofen, because so few people have died from overdosing on that drug…

“Acetaminophen overdose sends as many as 78,000 Americans to the emergency room annually and results in 33,000 hospitalizations a year, federal data shows. Acetaminophen is also the nation’s leading cause of acute liver failure, according to data from an ongoing study funded by the National Institutes for Health.”

A visitor to this website, R.M.D., offered this observation:

“In my experience, stomach bleeding problems from too much aspirin are usually accompanied by stomach discomfort and sometimes pain. These are a warning to discontinue the aspirin and see a doctor, particularly if the symptoms continue. Usually at this point any damage to the stomach is reversible.

“I don’t believe the same is true for acetaminophen. I think, perhaps incorrectly, that when you begin to get symptoms of liver problems from too much acetaminophen, the damage has already been done and may be too severe to be reversed. In any event I believe that aspirin used in moderation as directed on the label is safer than acetaminophen unless you have a history of GI bleeding.

“If you drink alcohol on a daily basis, you should probably stay away from acetaminophen and limit your use of all NSAIDs.”

R.M.D.’s advice to avoid alcohol if you take acetaminophen is wise. The FDA has known about the dangers of mixing alcohol with acetaminophen since the 1970s. It wasn’t until 1994, though, that an alcohol alert was added to Tylenol products. By the way, aspirin does not always alert people to stomach damage. We have heard from people who developed a bleeding ulcer without any warning. Here is a link to just such a story.

How Much Acetaminophen Is in One Pill?

The FDA has been even slower to reduce the amount of acetaminophen in each pill. Some experts have called on the FDA to permit no more than 325 mg in a tablet rather than the 500 mg found in “extra-strength” pills. Some acetaminophen products contain as much as 650 mg. Unfortunately, the FDA has been dragging its feet on recommendations by drug safety experts. One bright spot is that J&J voluntarily lowered the recommended dose to 3,000 mg on its Tylenol labels. Sadly, generic manufacturers of acetaminophen have not all followed suit.

Bottom Line: Acetaminophen Is Dangerous in High Doses

When used appropriately, in doses of 3,000 mg or less a day for short periods of time, acetaminophen appears to be reasonably safe. When taken in doses over 4,000 mg, even for just a few days, the liver could be harmed. This is especially true if you drink alcohol during the same time frame. And just because you see appealing advertising campaigns touting Tylenol as “the # 1 doctor recommended brand of pain reliever for over 20 years,” do not assume that means acetaminophen is super safe.

Here are some other comments from visitors to this website:

Sunny shares a very sad story:

“I had a neighbor who died from liver damage from overuse of acetaminophen. And I had severe liver damage from Cymbalta.

“Always, always, research what you are taking and the interactions with other drugs. Pharmacists are more knowledgeable than doctors, who may not always be aware of all the meds that you’re on. Always tell them what OTC meds and supplements you take, and keep your scripts at the same pharmacy, because the pharmacists are much more aware of drug interaction than doctors, I think.”

Kdelphi points up a problem when acetaminophen is an ingredient in so many diverse products:

“Acetaminophen has been pushed by the medical/pharmaceutical community for decades as ‘the safest one’–this drug finds its way into cold medicines, pain medications (including narcotics like oxycodone), allergy medicines and you name it…it is not really all that difficult to exceed the limit. I think we need to demand acetaminophen-free versions of medicines…Is there an acetaminophen lobby or something?”

Will H. points out the problem our reader was worried about. Remember, she was taking up to eight Tylenol Extra Strength pills daily plus Tylenol PM:

“I have been preaching against Tylenol since the 70s when the massive television push for it took off. Many of the ads pointed out so-called dangers of aspirin, magnifying them out of all proportion. I have never taken any medicine containing acetaminophen due to the danger to the liver. Since so many of the OTC medicines, particularly cold medicines, contain acetaminophen and the range of a safe dosage is so small, people are overdosing without realizing it.”

Learn More:

To find out which medicines you take contain acetaminophen and how much, check this ProPublica tool.

Describe your own positive or negative acetaminophen experience below in the comment section. And please share this article with friends and family.

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Some people find that non-drug approaches for pain relief such as acupuncture or chiropractic can ease discomfort. Anti-inflammatory herbs such as ashwagandha, Boswellia, ginger or turmeric may also help.

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