Acetaminophen dosage and benefit, side effects, safety, danger, risks, known by brand name Tylenol
Natural and alternative treatment to prevent damage and harm

September 1, 2017 by Ray Sahelian, M.D.

Acetaminophen is a common over the counter pain medicine. It is present in hundreds of painkiller products and may sometimes be unsafe even when used at the maximum daily doses recommended on package labeling. Acetaminophen (APAP) is the most common drug overdose in pregnancy. Acetaminophen (Tylenol by Johnson and Johnson, others) isn't a NSAID, but it sometimes does reduce pain and fever. Unlike NSAIDs, however, this medication does not reduce inflammation.
   The words acetaminophen and paracetamol both come from the chemical names for the compound: N-acetyl-para-aminophenol and para-acetyl-amino-phenol. In some contexts, it is shortened to apap, for N-acetyl-para-amino-phenol.
   Despite years of educational campaigns and other federal actions, acetaminophen is the leading cause of liver failure in the U.S., sending more than 50,000 people to the emergency room each year. One wonders why it is still available without a prescription whereas some natural herbs and supplements, that have a significantly better safety profile, have been removed from the market.

If you're plagued with a headache, sinus congestion or body aches, you may find the common pain reliever acetaminophen in more than one medication you take for relief. After all, it is found in more than 600 over-the-counter and prescription medications, according to the U.S. Food and Drug Administration.

A 2015 study in Psychological Science has found that acetaminophen, the main ingredient in Tylenol, most forms of Midol and more than 600 other medicines, reduces not only pain but pleasure, as well. It was already known that acetaminophen blunted psychological pain. But new research finds it also blunts joy -- in other words, that it narrows the range of feelings experienced.

Natural treatment to prevent acetaminophen toxicity
Eur J Pharmacol. 2014. Insights in the mechanism underlying the protective effect of α-lipoic acid against acetaminophen-hepatotoxicity. Acetaminophen (APAP) is one of the most widely used analgesic antipyretic drugs and is a major cause of acute liver failure at overdose. The aim of this study is to investigate the possible protective effect of α-lipoic acid (α-LA, 20 or 100mg/kg administered simultaneously or after 1.5h) against APAP-induced hepatotoxicity in rats. Administration of APAP resulted in elevation of serum ALT and hepatic malondialdehyde (MDA) content, as well as decrease in hepatic glutathione (GSH) content. In addition, elevation in hepatic hemeoxygenase-1 and NADPH oxidase expression was observed accompanied with a significant reduction in glutathione synthase and cystathionine-beta-synthase (CβS) expression. Furthermore, nuclear factor kappa-B (NF-κB) activity was enhanced in APAP-treated rats. Administration of the standard APAP antidote; N-acetylcysteine (NAC, 1200mg/kg) or α-LA (20mg/kg), simultaneously or 1.5h after APAP, ameliorated APAP-induced alterations in liver function, oxidant and inflammatory markers. Importantly, simultaneous administration of NAC or α-LA (20mg/kg) was more protective than their later administration. However, the beneficial effect of α-LA was lost at higher dose level (100mg/kg). Taken together, the beneficial effects of α-lipoic acid (20mg/kg) were comparable to those of NAC which provides a new possible treatment for APAP-induced hepatotoxicity in patients who cannot tolerate NAC. However, careful dose selection is warranted since the beneficial effects of α-LA were lost at higher doses.

Pathophysiology 2014. Quercetin protects against acetaminophen-induced hepatorenal toxicity by reducing reactive oxygen and nitrogen species. Our results suggest that the protective role of quercetin in the prevention of APAP-induced hepatorenal toxicity in rats was associated with the decrease of oxidative and nitrosative stress in hepatic and renal tissues as well as its capacity to improve the mitochondrial energy production.

Drug Metabolism Dispos. 2014. Efficacy of Wuzhi Tablet (Schisandra Sphenanthera Extract) on Acetaminophen-induced Hepatotoxicity through a Mechanism Distinct from N-acetylcysteine.

Q. I would like to use acetylcysteine to protect my liver from the amount of acetamenophin I am required to take on a daily basis due to my injuries. How much would I need to take of acetylcysteine?
   A. We have not seen any studies regarding the long term use of acetaminophen along with Acetylcysteine, however a dose of 100 mg a day would seem reasonable.

Acetaminophen safety, risks, liver harm - side effects, toxicity
Acetaminophen is one of the most common agents deliberately ingested in self-poisoning episodes and a leading cause of acute liver failure in the western world. Acetyl L Cysteine is widely acknowledged as the antidote of choice for this poisoning. Activated charcoal is used in cases of poisoning.
   Taken occasionally and in dosages less than 500 mg, acetaminophen has few side effects and is generally safe. However, if you frequently take more than is recommended adverse reactions can occur. Taking a large dose with alcohol increases the side effect risk and can lead to sudden and severe problems, such as liver failure. Acetaminophen is included in many different medications for pain, headaches, colds and sleep aids. Be sure to read the ingredients listed for all your medications to make sure you are not consuming more than you realize.
   Additional acetaminophen side effects include diarrhea; increased sweating; loss of appetite; nausea or vomiting ; stomach cramps or pain; swelling, pain, or tenderness in the upper abdomen or stomach area. Painkillers containing the ingredient acetaminophen can cause a potentially deadly skin rash known as Stevens-Johnson Syndrome.

There is an increased risk for lymphoma and myelodysplastic syndrome, or MDS.

2010 - May cause an increase in wheezing or asthma symptoms in children. American Journal of Respiratory and Critical Care Medicine 2010.

Acetaminophen and liver toxicity, failure
More than a third of healthy adults starting acetaminophen / paracetamol at the maximum recommended daily dosage of 4 grams will exhibit ALT liver enzyme elevations. The lead researcher is Dr. Paul B. Watkins, from the University of North Carolina in Chapel Hill. Dr. Watkins's study involved 145 healthy adults who were randomized to receive acetaminophen alone, acetaminophen plus opioid in one of three combinations, or placebo for 14 days. In all of the acetaminophen groups, the dosage was 4 g/day. No ALT elevations greater than three times the upper limit of normal were seen in the placebo group. By contrast, the incidence of such elevations ranged from 31% to 44% in the four groups receiving the painkiller. As noted, treatment with opioids did not further increase the ALT elevation seen with acetaminophen. Serum acetaminophen levels were usually not measurable at the time of the elevation. JAMA 2006.

In patients with acute liver failure, a test can determine whether acetaminophen toxicity is involved. More than 56,000 emergency room visits and nearly 500 deaths in the US each year are attributed to acetaminophen toxicity, owing to either intentional or unintentional overdoses. Acetaminophen toxicity is currently the most common cause of acute liver failure in the US and Europe. Although intentional overdose is fairly easy to diagnose, in unintentional overdoses, the diagnosis can be elusive, leading to a delay in the administration of potentially life-saving treatment. In animal and human studies, "serum acetaminophen-protein adducts" or mutations, are specific biomarkers for drug-related toxicity. Gastroenterology 2006.

Osteoarthritis treatment
The evidence to date suggests that NSAIDs are superior to acetaminophen for improving knee and hip pain in people with osteoarthritis. In fact, it is possible that chronic use of acetaminophen could harm or cause damage to articular tissue, or, at the least, harm liver tissue. For osteoarthritis pain and joint health, glucosamine and chondroitin are preferred. Acetaminophen has limited benefits in patients with osteoarthritis.

Acetaminophen and tooth extraction
Paracetamol (Panadol) , the pain killer known as acetaminophen in the U.S. and sold under the trade names Tylenol in the US and Panadol in the UK, is an effective treatment for the pain following wisdom tooth extraction.

Acetaminophen Drug Recall
2006 - Perrigo Co.. a major manufacturer of store-brand acetaminophen, recalled 11 million bottles of the pain-relieving pills after discovering some acetaminophen pills were contaminated with metal fragments. There were no immediate reports of injuries or illness. Perrigo Co. said it discovered the metal bits during quality-control checks. The drug company passed 70 million acetaminophen pills through a metal detector and discovered the metal in about 200 caplets. The fragments ranged in size from “microdots” to portions of wire one-third of an inch long. Perrigo company did not disclose the chains for which it manufactures the store-brand product.

Questions
Q. People who are addicted to pain medications, such as hydrocodone, often take way too much APAP (acetaminophen) in the process. For over a year, I was one of them. I averaged over 30 10/325 tablets a day, often taking much more (several times 80 or more). Knowing what I was doing to my liver, I researched the procedure used in the ER for acetaminophen overdose and proceeded to treat myself accordingly, using OTC NAC (n-acetylcysteine). I am thankfully free of this addiction now (over 9 months), but still communicate with others in the throws of it. I have suggested to them that they should stock up on N-acetyl Cysteine and use it if necessary (obviously the right solution is to go straight to the ER if you've taken over 10g of acetaminophen, but we both know that may not happen with these folks). When I pointed this out, I was overwhelmingly ridiculed and dismissed by those who said the NAC available over the counter is nothing like that used in the ER. I know there is probably a difference, but given that one is not going to seek proper medical treatment, isn't the NAC we have access to a great alternative?
   A. Based on my limited knowledge, since I have not seen head to head research comparisons, I tend to think that the benefits of oral and intravenous NAC would not be too different, but I have no proof of this.

Interactions with herbs and supplements
Q. I recently read that taking echinacea with acetaminophen "can severely damage your liver" and that taking kava or echinacea while on a statin med for cholesterol "can trigger potentially fatal liver damage". (These statements were attributed to a book by George Grossberg, M.D.) Are these statements supported by the available evidence? I am on a statin and sometimes take acetaminophen for arthritis pain.
   A. We have not heard of echinacea herb causing serious liver harm, but perhaps it may in rare cases. Acetaminophen can certainly harm the liver, statins could, and kava may in rare cases. The combinations would not be a good idea.

Q. I recently started taking hoodia supplements for weight loss and was wondering if there was any information regarding the use of this herbal extract along with acetaminophen.
   A. We are not aware of any such studies or interactions.