Tylenol Isn’t So Safe, But At Least It Works, Right?
https://www.acsh.org/news/2017/09/18/tylenol-isnt-so-safe-least-it-works-right-11827
I’m not a big fan of Tylenol, which becomes rather obvious if you read the first part of this two-part series. For a drug that is so widely used, it is quite easy to consume enough, accidentally or otherwise, to take enough to suffer a toxic overdose due to irreversible liver damage.
But drugs cannot be judged by safety alone. Both the good and the bad – benefits and risks – must be taken into account to get the true measure of the quality of a drug. So if Tylenol isn’t all that safe, you might expect that, at the very least, it should work well. Otherwise, why would so many people be taking it?
That’s the $64,000 question, and here’s the answer. In reality, Tylenol doesn’t work very well at all, and there is plenty of evidence to back this up, especially in systematic Cochrane Reviews – highly regarded, evidence-based reviews that carefully evaluate the quality of data in multiple studies. Here are some representative analyses.
Osteoarthritis of the Knee and Hip
A group of five pain specialists and pharmacologists in Denmark examined seven studies of patients with hip- or knee osteoarthritis. All seven included a comparison between acetaminophen (used continuously for more than two weeks) with placebo. The review, entitled “Acetaminophen for Chronic Pain: A Systematic Review on Efficacy” was published in the journal Basic & Clinical Pharmacology & Toxicology. The conclusion:
“All included studies showed no or little efficacy with dubious clinical relevance. In conclusion, there is little evidence to support the efficacy of acetaminophen treatment in patients with chronic pain conditions. Assessment of continuous efficacy in the many patients using acetaminophen worldwide is recommended.”
Z. Ennis, et. al., Basic & Clinical Pharmacology & Toxicology, 2016, 118, 184–189
Well, that doesn’t sound so marvelous. Perhaps it’s just a single bad paper. Or not.
Acute and Chronic Lower Back Pain
A 2016 Cochrane Review entitled “Paracetamol for low back pain” (1) examined the utility of Tylenol in treating lower back pain. The review included three trials with a total of 1825 participants, mostly middle-aged, who had acute back pain, and another trial in which the participants had lower back pain for more than six weeks. All of the trials also had a placebo arm. The drug was administered either orally or by IV in doses that ranged from one gram to four grams. How did that work? Ouch.
“We found high-quality evidence that paracetamol (4 g per day) is no better than placebo for relieving acute LBP in either the short or longer term. It also worked no better than placebo on the other aspects studied, such as quality of life and sleep quality.”
B.Saragiotto et. al., Cochrane Review, June 2016
Back Pain, and Hip and Knee Osteoarthritis
The hits keep coming. A 2015 review in the British Medical Journal entitled “Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo-controlled trials” examined reports of 13 randomized trials. The review examined several measures of pain relief: pain intensity, disability, and quality of life in people with low back pain, and hip or knee osteoarthritis. and concluded:
“Paracetamol is ineffective in the treatment of low back pain and provides minimal short term benefit for people with osteoarthritis. These results support the reconsideration of recommendations to use paracetamol for patients with low back pain and osteoarthritis of the hip or knee in clinical practice guidelines.”
M. Ferreira, et. al, BMJ 2015; 350
Headaches
OK, so it doesn’t work for back pain or arthritis, but that’s OK because most people use it for headaches. Well, it works. Sort of. A Cochrane Review entitled “Oral paracetamol for treatment of acute episodic tension-type headache in adults” looks at just that. This may surprise you.
Things look OK at the beginning of the results sections: “The International Headache Society recommends the outcome of being pain free two hours after taking a medicine. The outcome of being pain free or having only mild pain at two hours was reported by 59 in 100 people taking paracetamol 1000 mg…”
It may not be perfect, but a 59% response isn’t all that terrible. Until you read the rest of the sentence: “…and in 49 out of 100 people taking placebo. This means that only 10 in 100 or 10% of people benefited because of paracetamol 1000 mg.
Now, *that’s* pretty bad. Of the 59 of you who are getting headache relief from the stuff either believed that their headache went away, or it went away within two hours on its own, not from the drug. So, the real efficacy of Tylenol is 10%. That’s enough to give you a headache.
Colds
Tylenol is often used to treat symptoms of a common cold. For a cold, the data are not as conclusive as in the studies about, but there is little evidence that acetaminophen is effective.
“Acetaminophen may help relieve nasal obstruction and rhinorrhoea [runny nose] but does not appear to improve some other cold symptoms (including sore throat, malaise, sneezing, and cough). However, two of the four included studies in this review were small and allocation concealment was unclear in all four studies. The data in this review do not provide sufficient evidence to inform practice regarding the use of acetaminophen for the common cold in adults.”
S . Li, et. al, “Acetaminophen (also called paracetamol) for the common cold in adults.” Cochrane Review, June 2013
Tooth Pain
For a pain following wisdom tooth extraction, Tylenol is inferior when compared with ibuprofen (Advil), but when two are combined there seems to be a synergistic effect.
“There is high quality evidence that ibuprofen is superior to paracetamol at doses of 200 mg to 512 mg and 600 mg to 1000 mg respectively based on pain relief and use of rescue medication data collected at six hours postoperatively. The majority of this evidence (five out of six trials) compared ibuprofen 400 mg with paracetamol 1000 mg, these are the most frequently prescribed doses in clinical practice. The novel combination drug is showing encouraging results based on the outcomes from two trials when compared to the single drugs.”
E. Bailey et. al, “Ibuprofen versus paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth Cochrane Review, December 2013
Fever
Tylenol is given to children to lower fever, and it does so successfully. So do NSAIDs, such as aspirin and ibuprofen. There is some indication that giving the two together or alternating the drugs may be more effective, but the evidence is weak.
“Paracetamol (also known as acetaminophen) and ibuprofen lower the child’s temperature and relieve their discomfort…. There is some evidence that both alternating and combined antipyretic therapy may be more effective at reducing temperatures than monotherapy alone. However, the evidence for improvements in measures of child discomfort remains inconclusive.”
T. Wong, et.al., “Alternating and combined antipyretics for treatment of fever in children.” Cochrane Review, October 2013
This article is not intended to be a comprehensive examination of every review about the efficacy of acetaminophen. There are undoubtedly studies that demonstrate efficacy, however, I chose to include (mainly) information from Cochrane, since it is widely considered to be a high-quality source for evidence-based medicine.
To wrap this up: acetaminophen largely ineffective. And I have already demonstrated why it is only marginally. This makes it one lousy drug.
Note:
(1) Paracetamol is another name for acetaminophen, the generic name of Tylenol. It is commonly used in Britain.
If you own Johnson and Johnson stock you probably have enough problems on your hands. The company keeps getting hammered by lawsuits alleging that talc in baby powder has given women cancer (1). So you sure don’t need me smacking down Tylenol, which had worldwide sales of almost $2 billion in 2016.
But, don’t blame me. This is not my quote. It’s part of a written interview I did back in July with Aric Hausknecht, M.D, “Pain In The Time Of Opioid Denial: An Interview With Aric Hausknecht, M.D.”
“Tylenol Is By Far The Most Dangerous Drug Ever Made”
Aric Hausknecht, M.D. July 30, 2017
Why would Dr. Hausknecht, a New York neurologist and pain management specialist, say this? Taken out of context, such a sweeping statement may seem to be hyperbolic. The most dangerous drug ever made? I asked him to elaborate. He did:
“Each year a substantial number of Americans experience intentional and unintentional Tylenol (acetaminophen) associated overdoses that can result in serious morbidity and mortality. Analysis of national databases show that acetaminophen-associated overdoses account for about 50,000 emergency room visits and 25,000 hospitalizations yearly. Acetaminophen is the nation’s leading cause of acute liver failure, according to data from an ongoing study funded by the National Institutes for Health. Analysis of national mortality files shows about 450 deaths occur each year from acetaminophen-associated overdoses; 100 of these are unintentional.”
Therapeutic Index – A cornerstone of pharmacology
When evaluating drug toxicity, a critical parameter is called the therapeutic index (TI). The TI is the ratio of the toxic dose to the effective dose. Obviously, the higher the TI the better, since the greater the separation of the therapeutic and toxic doses, the less likely an overdose. Here are some examples of low TI drugs:
- Lithium (bipolar disorder)
- Warfarin (blood thinner)
- Theophylline (asthma)
- Digoxin (various heart conditions)
And some examples of high TI drugs:
- Benadryl (diphenhydramine, antihistamine, sleep aid)
- Valium (sedative, hypnotic) (2)
- Neurontin (gabapentin, restless leg syndrome, multiple off-label neurological indications)
Tylenol (acetaminophen) an analgesic (pain reliever) gets a free pass in the minds of many people because it doesn’t come with the liabilities of the NSAIDs, such as aspirin and ibuprofen – bleeding, heartburn, kidney toxicity. ulcers, and salicylate allergy. The absence of gastrointestinal toxicity is responsible for the widespread perception that Tylenol is safer. In some ways it is, but in others, it is not. It may leave your stomach alone, but not your liver.
Dr. Hausknecht’s statistics may seem puzzling. How can there be 50,000 emergency room visits and 25,000 hospitalizations, yet only 450 deaths per year? This is because, when treated in time, irreversible liver damage from an acute overdose of acetaminophen can be prevented. There is an antidote called N-acetylcysteine. But the danger of the drug is not only from acute doses. Both acute and chronic use of acetaminophen can lead to permanent liver damage, not because acetaminophen itself is toxic, but because the liver converts it into something that is (Figure 1), sealing its own fate in the process. (Apologies for the biochemistry.)
Figure 1: Metabolic activation and detoxification of acetaminophen. Oxidation by liver enzymes forms N-acetylbenzoquinoneimine, a chemically reactive, toxic molecule. The carbon atom (red arrow) irreversibly “attacks” various proteins in the liver. The antidote, N-acetylcysteine sops up (deactivates) the benzoquinone imine, but only if given in time. It does not reverse liver damage.
So, what is the therapeutic index for Tylenol? You may be rather surprised. Before 2011 the maximum daily dose of acetaminophen recommenced by the FDA was 4,000 mg. It is now 3,000 mg. The estimated lethal dose of the drug is 10 grams in one day, which is not terribly different from the maximum daily dose. The TI is thus about 3, which is pretty bad, especially compared to other drugs which are perceived as far more dangerous:
References:
a) http://www.acutetox.eu/pdf_human_short/1-Acetaminophen%20revised.pdf
b) https://medlineplus.gov/ency/article/002542.htm
c) https://www.fda.gov/ohrms/dockets/dailys/03/Aug03/082903/03p-0398-cp0000…att-6-vol1.pdf
d) https://www.ncbi.nlm.nih.gov/pubmed/357765
** Therapeutic index (TI) is an approximate, but indicative measure of the likelihood of a toxic or lethal overdose. It is not a measure of absolute toxicity, rather, the safety margin between therapeutic and toxic or lethal doses.
Approximate therapeutic indexes for some common drugs. The higher the TI, the lower probability of an overdose.
Rather interesting that the CDC, which has inserted itself firmly up your doctor’s anus for writing scripts for Valium or hydrocodone, is only too happy to recommend that pain patients take a drug that is more likely to cause an overdose than either of them.
“Several nonopioid pharmacologic therapies (including acetaminophen, NSAIDs, and selected antidepressants and anticonvulsants) are effective for chronic pain. In particular, acetaminophen and NSAIDs can be useful for arthritis and low back pain…”
CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016
Next: “So, Tylenol isn’t that safe, but at least it works, right?”
NOTES:
(1) It would seem that evidence of harm is totally irrelevant in the courtroom. It is far from clear that talc is harmful. But it is even further from clear that there is *any* proof that Eva Echeverria, a victim of ovarian cancer who used baby powder her whole life, contracted the disease from the powder. Lawyers 1, Science 0.
(2) It is very difficult to die from a Valium overdose in the absence of alcohol, opioids or other central nervous system depressants. (See: “Can Valium Kill You?”). In two case studies, people survived overdoses of 500 and 2,000 mg (50 and 400 five milligram pills, respectively). But, 50 regular strength Tylenol pills (16.25 g) is approximately twice the estimated lethal dose. Yes, a single dose of 500 Valium pills is less dangerous than 50 Tylenol pills.
Filed under: General Problems
How about that.50,000 emergency room visits, and 25,000 hospitalizations per year from the cdc favorite useless drug,Tylenol, including 450 deaths in that same time frame. Do they know what actually helps pain and leads to 0 hospitalizations and NO deaths,ever? KRATOM herb ,the natural herb used effectively by millions for pain.An herb That has been in use for hundreds of years, long before big pharma in all their wisdom started flooding the market with deadly drugs like Tylenol.Do you know what other herb has been in use for thousands of years for pain and other conditions,without any deaths or toxic problems that lead to hospitalization? Cannabis.
Now which two substances do they want to outlaw and deprive millions of safe natural relief. Kratom and cannabis.Surprise,surprise.
Cdc does a lot of good,and so does big pharma.But for two entities that have so many brilliant people working for them,they act awfully ignorant when it comes to natural,safe substances.Its they’re way or the highway.Mankind has used natural substances long before either entity existed.They need to listen to the people in these matters,and they may discover less of a need will exist for dangerous synthetic drugs such as Tylenol. They want to restrict the very thing that can reduce the usage of such useless dangerous drugs, and reduce the suffering of millions without destroying there livers and lives.