What exactly is hepatotoxicity, and why should I be worried?

The liver is a vital organ that is responsible for many body functions, including blood cell composition, breakdown of nutrients we eat, balancing cholesterols, and ridding our body of foreign chemicals, such as alcohol and drugs.
Hepatotoxicity is damage that occurs to the liver by chemical means. Medications that we use every day can ultimately be damaging our liver!
Unfortunately, hepatotoxicity from commonly known drugs is often a cause of liver injury. It is estimated as many as 1000 drugs can be blamed for some form of liver damage.
The liver’s role in detoxification makes it especially vulnerable to damaging substances. Liver cells, hepatocytes, can be injured by various pathways depending on the type of drug being metabolized. Reactive particles can destruct the cellular components of the hepatocytes, leading to cell death. Other metabolites alter liver enzymes responsible for drug metabolism leading to toxicity. Drug fragments can also bind to liver proteins initiating an autoimmune attack on the liver tissue.
Effects of hepatotoxicity can be seen throughout the body. General symptoms include: nausea, vomiting, upper right stomach pain, loss of appetite, brown urine, and yellowing of the skin and eyes (jaundice.) It is important to note these changes early and notify the health-care provider immediately if they are experienced. Early intervention is the safest way to limit damage to the liver!
Who is at risk for hepatotoxicity? EVERYONE! It may be a patient you are monitoring, a family member you are educating, or yourself. Concerns extend far beyond high dosages of prescription medications. Hepatotoxicity can result from combining multiple drugs, alcohol consumption with medications, genetic predispositions, age-related metabolism rates, and underlying diseases. Over-the-counter products, such as Tylenol, and herbal remedies, that are often considered “safe”, play a HUGE role in liver damage.
The key to lowering your risk is EDUCATION. Knowledge about hepatotoxicity is critical to keeping EVERYONE safe.

Kaplowitz, N. (2004). Drug-induced liver injury. Clinical Infectious Diseases: An Official Publication Of The Infectious Diseases Society Of America, 38 Suppl 2S44-8.

More information on hepatotoxicity, like specific symptoms to look out for can be found here: http://www.liverdisordersfocus.com/articles/liver-disorders/drug-induced-liver-damage.php

Sunday, October 18, 2009

Are You at Risk for Over-the-Counter Hepatotoxicity?

Below are factors that contribute to unintentional overdoses of over-the-counter (OTC) products: 

1. Consumers perceive that OTC products are extremely safe and not likely to lead to serious toxicity. The marketing of OTC products emphasizes their safety and this perception may be reinforced by the availability of package sizes with large numbers of pills.

2. Consumers do not read the labels or follow the directions for use on OTC and prescription products.

3. Some of the prescription products are not adequately labeled to identify acetaminophen as an ingredient. Acetaminophen is often labeled as APAP on the prescription containers.

4. Consumers are not aware that acetaminophen can cause serious liver injury, in part because product labels do not adequately warn of this problem.

5. Consumers are not aware that acetaminophen is present in many OTC and prescription products and are not aware that they are exceeding the maximum daily dose.

6. Some populations (e.g., certain alcohol users and people with liver disease) are more susceptible to hepatic injury.

7. The symptoms of acetaminophen overdose may not appear for up to three days, so people may continue to take acetaminophen and increase the damage. The symptoms of liver injury may mimic the condition that they are treating (e.g., flu symptoms).

8. Because patients may not get adequate pain relief after taking the recommended dosage of acetaminophen, they may take more than the recommended amount or use other products that also contain acetaminophen.

9. Patients develop tolerance to narcotics and need to increase the dose of prescription combination products. If they do this on their own, they may not realize that they are increasing the dose of acetaminophen to toxic levels.

10. Combination narcotic products are commonly used because of limited non-narcotic options and greater restrictions on availability for higher scheduled single-ingredient narcotic analgesics.

For more information, please read the full report by The Acetominophen Hepatotoxicity Group.


The Acetaminophen Hepatotoxicity Working Group Center for Drug and Evaluation Research, F. D. (2008). Recommendations for FDA Interventions to Decrease the Occurence of Acetaminophen Hepatotoxicity.


  1. This is wonderful information. Is there a place online where we can check to make sure we are not taking medications that should not be taken at the same time. If I have a prescription from my doctor and then start taking something over the counter how do I know if they can be taken over the same period of time other than contacting my doctor to ask them?

    Crystal Carlson

  2. The information about acetaminophen was really interesting. I'll be looking at Tylenol differently from now on, haha.

    The consequences about the liver injury was surprising.

  3. Crystal,
    Pharmacists are valuable resources about possible interactions when purchasing your over-the-counter products. Make sure to READ THE LABELS of what you buy to make sure you know what you are taking and the risk associated with your prescriptions. You can also find valuable information about your specific medications on the FDA's website at www.fda.gov

    The possibilities of liver damage through the use of acetominophen are not well known to consumers. Fortunately, you now have the ability to recognize serious drug effects such as these and avoid complications. Now that you're in the know, who else can benefit from this information? Maybe a friend, colleague, or those closest to you?

  4. I found this information very helpful. Thank you for sharing it.

  5. This is valuable information. Until you are made aware of the trouble acetaminophen has on your liver, then you do not know how many over the counter products contain acetaminophen. It is troublesome that you may take some cold medicine and then a couple of excedrin for a headache and be putting yourself in jeopardy! Acetaminophen is NOT just in Tylenol! Thank you for such a comprehensive site!

  6. That is such a major part of the problem with acetaminophen toxicity- people don't realize they can overdose when taking multiple medications! It is shocking when you realize how serious this situation is!! Think of others you know who do not know this...Is there someone else who can benefit from this information?

  7. Good information to know. It makes you think before popping a Tylenol/Advil before bedtime just for "maintenance". One never suspects that OTC's have the same danger of long-term side effects that prescription meds do.


Hepatotoxicity: Where We've Been, Where We Are, Where We're Going


Hepatotoxicity dates back to nearly 100 years. Just recently, they have discovered that some of the most common drugs can cause liver injury. These drugs are currently well known to the public and used by a majority of the population. The drugs in question are known as non-steroid anti-inflammatory drugs (NSAIDS), statins, anti-diabetics, and acetaminophen.

- Acetaminophen was known to cause liver damage in 1943, if not taken in therapeutic range. Even when taken appropriately, can cause hepatotoxicity if taken with other medications.
- The anti-diabetic drug, troglitazone, was the first drug to bring light to hepatotoxicity and the long-term causes it can have on the liver.


Hundreds of articles exist on the effects of drugs on the liver. The drug industry has been hit hard with removal of drugs from the market that cause liver damage. Liver hepatotoxicity is one of the most common reasons that drugs are withdrawn from the public's use. Even doses in the therapeutic range, have been known to cause toxicity of the liver. Although these drugs were known to work effectively, they were shown to cause severe liver damage, liver transplant, or death.

In 2006, the FDA added guidelines to follow if the immune system falls below a certain range. Liver enzymes should be tested in order to keep patients safe. This is currently the only way to diagnosis liver hepatoxicity, at least the most efficient way.

Recently, the public has become aware of acetaminophen related hepatotoxicity. One controversy on OTC drugs is the drug-drug interactions. The public is not as educated as they should be on the ease of overdosing on OTC drugs. As healthcare professionals, it should be an important goal to educate patients on liver safety.


Drug companies will have a never-ending battle with regulating the side effects of drugs. It could be considered a catch 22, drugs can dramatically improve ones life and at the same time be a silent killer. The FDA has taken steps to educate the public on these drugs, but the warnings do not seem to be eye catching enough.

Studies show that there is a possible genetic link to drug induced liver injury. Science Daily (2009) studies show that acetaminophen is toxic if taken in high doses, but a link exists showing that toxicity is more likely due to genetics. The study suggests that finding the genetic marker will help create safer drugs in the future. Studies also suggest that some patients become more susceptible due to their environmental factors.

Current preclinical and clinical liver safety testing does an excellent job in keeping the public safe from drugs capable of causing various forms of liver injury.

In any case, the FDA will constantly be on alert for drugs and their contraindications for hepatotoxicity. Healthcare professionals will need to be aware of the ever-changing revisions to drugs and safety changes.


Lucena, M., García-Cortés, M., Cueto, R., Lopez-Duran, J., & Andrade, R. (2008). Assessment of drug-induced liver injury in clinical practice. Fundamental & Clinical Pharmacology, 22(2), 141-158. http://search.ebscohost.com/

Watkins, P. (2005). Idiosyncratic liver injury: challenges and approaches. Toxicologic Pathology, 33(1), 1-5. http://search.ebscohost.com/

Fontana R, Watkins P, Bonkovsky H, et al. Drug-Induced Liver Injury Network (DILIN) prospective study: rationale, design and conduct. Drug Safety: An International Journal Of Medical Toxicology And Drug Experience [serial online]. 2009;32(1):55-68. Available from: MEDLINE

Ipswich, MA. Accessed October 16, 2009.Lee W, Senior J. Recognizing drug-induced liver injury: current problems, possible solutions. Toxicologic Pathology [serial online]. 2005;33(1):155-164. Available from: MEDLINE, Ipswich, MA. Accessed October 16, 2009.009.