Acetaminophen (APAP) is one of the most widely used over-the-counter analgesics in the world. It is most commonly known as Tylenol. Despite its popularity, there is growing concern over the potential for acetaminophen liver toxicity, which can cause serious liver injury. In fact, APAP hepatotoxicity is now the leading cause of acute liver failure in the United States and other nations. This has led some experts to question whether APAP should continue to be used as a first-line pain reliever.

The article “Acetaminophen (APAP) hepatotoxicity – Isn’t it time for APAP to go away?” and written by Dr. William M. Lee, published in 2017 in the Journal of Hepatology, examines the issue of APAP hepatotoxicity in detail. For you and me, that means liver toxicity that leads to impaired liver function or even death.

In the article, Dr. Lee argues that APAP is not only dangerous, but also unnecessary in many cases. We do tend to pop Tylenol like candy and there’s mounting evidence that it really isn’t all that effective for pain. 

Whether you are into science or not, the fact is that APAP as a drug, needs some explaining.  In his landmark piece, Dr. Lee first discusses the mechanism by which APAP causes liver injury. When APAP is metabolized in the liver, it produces a toxic byproduct called N-acetyl-p-benzoquinone imine (NAPQI).

Normally, this compound is quickly detoxified by the liver’s natural antioxidant defenses. However, in cases of APAP poisoning, overdose or chronic use, or in combination with alcohol, the liver’s ability to detoxify NAPQI can become overwhelmed. This can lead to liver damage, which can range from mild liver injury to acute liver failure.

Catie suffered from liver failure, then she went into acute liver failure, ultimately with multi organ failure.  In her medical records it shows they were planning to test from a genetic perspective to see if she was predisposed to an inability to process the toxins. I find myself wondering at times, how many are predisposed without realizing it, or what % of the public lacks knowledge about the fact that they could be predisposed?

Dr. Lee discusses the prevalence of APAP hepatotoxicity. He notes that despite efforts to reduce incidences of APAP overdose, the rate of APAP-related acute liver failure has remained stable over the past decade during his research period. This suggests that the current strategies for preventing APAP overdose are not working as well as they could.

Frankly it is not easy to go up against $250,000,000 in marketing funds for a drug that is commonly considered “safe” and convince people to take care, or use caution.  Sometimes we get that type of feedback at Catie’s Cause.  People just cannot fathom or they doubt  that an over the counter medication could take the life of a child or an adult.  Trust us, it can and does very regularly. 

In addition to discussing the dangers of APAP, Dr. Lee also examines the alternatives to APAP for pain relief. He notes that there are several other over-the-counter analgesics that are just as effective as APAP, but without the risk of liver injury. These include ibuprofen and naproxen, which are both non-steroidal anti-inflammatory drugs (NSAIDs).  These are not without side effects, but we deem those less injurious generally.  

It has become difficult to get a prescription for opioids due to the overuse, abuse and chronic addictive properties. In fact in 2022, 244 people each day died from an opioid, compared to 500 deaths per year from APAP.   The opioid deaths include legal and illegal forms of the drug.

Some doctors, including Dr. Lee,  feel they can be an alternative to APAP. While opioids have their own set of risks and drawbacks, they are generally considered to be safe and effective for short-term use. However, Dr. Lee cautions that the use of opioids for chronic pain management should be carefully considered, given the potential for addiction and other adverse effects. We agree. And clearly much has changed with opioid access since his research was conducted. 

In conclusion, Dr. Lee argues that it is time to reconsider the use of APAP as a first-line pain reliever. He notes that while APAP may be effective for pain relief, it comes with a significant risk of liver injury, especially with chronic use, poisoning, or unintentional overdose. Given the availability of safer alternatives, such as NSAIDs and even opioids when carefully prescribed and taken for a short term use, Dr. Lee suggests that APAP should be reserved for cases where these alternatives are not medically appropriate or effective.

The good news is that there are options in the pharma pipeline that might make it possible to get the relief needed from a pain drug, without the side effects of APAP.  Dr. Hernan Bazan and South Rampart Pharmaceuticals has a medication in clinical trials with the FDA that might do just that.  Let’s hope.

Overall, this article provides a compelling argument for rethinking the use of APAP in clinical practice. While APAP may have been a useful and popular pain reliever in the past, its potential for liver injury cannot be ignored. With the availability of safer alternatives, in our humble opinion, we agree with Dr. Lee, that it is time to move away from APAP and towards safer and more effective pain relief options.  But we would be reluctant to suggest opioids given their high death toll here in the US.