Acetylcysteine and high doses of Acetaminophen/Paracetamol

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Discussion Overview

The discussion centers on the use of Acetylcysteine (N-Acetylcysteine) in relation to high doses of acetaminophen (paracetamol), particularly in the context of treating COVID-19 symptoms such as persistent high fever. Participants explore the potential benefits and risks of combining these medications, as well as the appropriateness of prescribing Acetylcysteine for patients taking high doses of acetaminophen over extended periods.

Discussion Character

  • Exploratory
  • Debate/contested
  • Technical explanation

Main Points Raised

  • One participant describes their father's experience with high doses of acetaminophen for COVID-19 and questions whether Acetylcysteine should be prescribed to mitigate potential side effects.
  • Several participants mention finding journal articles related to the use of Acetylcysteine and acetaminophen, indicating a search for evidence on the topic.
  • Another participant notes that while Acetylcysteine is used for acetaminophen poisoning, its role in reducing side effects from therapeutic doses of acetaminophen remains unclear.
  • A participant references a study suggesting that Acetylcysteine does not influence the effectiveness of paracetamol, proposing that the two can be used together without diminishing each other's effects.
  • Concerns are raised about the potential for liver injury associated with therapeutic doses of acetaminophen, although some argue that evidence for significant hepatotoxicity is lacking in healthy individuals.
  • One participant suggests that the physician may not have considered alternative treatments for the patient's symptoms, raising questions about the management of the case.

Areas of Agreement / Disagreement

Participants express differing views on the appropriateness of prescribing Acetylcysteine alongside high doses of acetaminophen. While some suggest that the combination may be beneficial, others highlight the lack of consensus on its necessity and effectiveness in this context. The discussion remains unresolved regarding the best course of action for patients taking high doses of acetaminophen.

Contextual Notes

Participants reference various studies and articles, but there is no clear consensus on the implications of combining Acetylcysteine with acetaminophen, particularly regarding side effects and treatment efficacy. Limitations in the available evidence and varying interpretations of existing research contribute to the ongoing debate.

Wrichik Basu
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TL;DR
Should doctors prescribe Acetylcysteine to anyone (not only COVID patients) who is taking high doses (not overdose) of acetaminophen/paracetamol for a long period of time?
Acetylcysteine (or N-Acetylcysteine) is an important drug that is used to loosen thickened mucus in the lungs. In addition to that, it is also used for treating paracetamol/acetaminophen poisoning.

Many people who have contracted SARS-CoV-2 are suffering from very high fever for a long period of time. Doctors are prescribing high doses of acetaminophen (or paracetamol) as antipyretic for suppressing the fever. For example, take the case of my father. His fever started on 31st August; on 3rd September he tested positive for COVID-19 (in the RT-PCR test), and we had to admit him to the hospital on 8th September for persistent high fever. Since day one of the fever, he has been taking paracetamol, at first 4g a day (with a gap of 6 hours between two successive doses of 1g each) for three days, and thereafter 3g a day (gap of 8 hours between two successive doses). Currently, in the hospital, he is being given intravenous paracetamol at the same dose (3g a day). (Note that none of this was/is self-medication; the doctor has prescribed these doses). If a dose is missed, the fever is returning, the temperature reaching as high as 103°F.

While acetaminophen is required for suppressing the fever, high doses (not overdose) of this drug have ill-effects on kidney and liver. My father is not the only person who is taking such high doses of this drug. Our doctor agrees that there are side effects, but he is not bothered to do anything about the side-effects.

My question: should doctors prescribe Acetylcysteine to anyone (not only COVID patients) who is taking high doses of paracetamol for a long period of time? Is there any study which says this should be done? Any paper against this thought?

Edit (last paragraph): made my question a bit clearer.
 
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I googled Covid acetylcysteine and immediately came up with at least 5 journal articles on the topic. I’m assuming you can do the same.
 
TeethWhitener said:
I googled Covid acetylcysteine and immediately came up with at least 5 journal articles on the topic. I’m assuming you can do the same.
I wanted to know if acetylcysteine can reduce the side effects of acetaminophen, not how the drug can be used for treatment of COVID-19. I edited the question to make it a bit clearer.
 
I googled acetylcysteine acetaminophen and immediately came up with another handful of journal articles.
 
https://www.nhs.uk/news/medication/is-long-term-paracetamol-use-not-as-safe-as-we-thought/

https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.13656
Long‐term adverse effects of paracetamol – a review
J. C. McCrae, E. E. Morrison, I. M. MacIntyre, J. W. Dear, D. J. Webb
Br J Clin Pharmacol. 2018 Oct;84(10):2218-2230. doi: 10.1111/bcp.13656

"Over the past few decades, there have been several case reports and small studies implying a connection between the ingestion of therapeutic doses of paracetamol and liver injury 86. It has been known for many years that therapeutic paracetamol use (≤4 g d–1) has been associated with subclinical rises in liver injury markers 74. However, transient rises in alanine aminotransferase (ALT) can be secondary to many factors, such as exercise, vitamin intake, congestive heart failure, diabetes and medications such as aspirin, heparins and statins 87, 88. Whether such an enzyme rise results in clinically significant liver injury is less clear."

"There does not seem to be evidence for therapeutic paracetamol treatment causing hepatotoxicity, either in healthy individuals or chronic liver disease patients, with the exception of those in a poor nutritional state 98, 99."
 
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NAC (N-acetylcystiene ) is used as a standard ER treatment for Tylenol (acetminophen) poisoning in the US.

I cannot give medical advice, but drugs like Dexamethasone with azithromycin have been approved for Covid-19 treatment with good results. The point being that you should ask the physician what alternative treatments he has considered. And why the patient has not received them. There are other antipyretic drugs in use with Covid-19 patients.

What I'm saying: this yo-yo symptomology looks like the physician is out of answers. Or the patient has other comorbidities that prevent alternate drug therapy.

@atyy suggestions above seem helpful to me.
"There does not seem to be evidence for therapeutic paracetamol treatment causing hepatotoxicity, either in healthy individuals or chronic liver disease patients, with the exception of those in a poor nutritional state 98, 99."

... I.e., let it be.
 
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To answer your question: This study shows for the first time that paracetamol effectiveness is not influenced by N‐Acetylcysteine.

It looks as if they balance each other out so much that combinations of the two are actually recommended as a great call for doctors to make- with neither reducing the effectiveness of the other and one being protective against the other. Being protective doesn’t always mean reduced efficacy with pharmaceuticals; amazingly, many times a balance is found!

Very good question, I would have questioned it too at first.

And I wish your father a complete and speedy recovery!
 
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Fervent Freyja said:
It looks as if they balance each other out so much that combinations of the two are actually recommended as a great call for doctors to make- with neither reducing the effectiveness of the other and one being protective against the other. Being protective doesn’t always mean reduced efficacy with pharmaceuticals; amazingly, many times a balance is found!
Exactly what I was thinking!
 
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