Acetylcysteine and high doses of Acetaminophen/Paracetamol

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In summary, my father is taking high doses of paracetamol for a long period of time, and is suffering from high fever. Acetylcysteine is being prescribed to him to reduce the side effects of this treatment, but there are potential side effects.
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Wrichik Basu
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TL;DR Summary
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.
 
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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.
 
  • #4
I googled acetylcysteine acetaminophen and immediately came up with another handful of journal articles.
 
  • #5
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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What is Acetylcysteine?

Acetylcysteine is a medication that is commonly used as an antidote for acetaminophen (also known as paracetamol) overdose. It works by helping the body produce more glutathione, a substance that helps to break down toxic metabolites of acetaminophen.

What is the recommended dose of Acetylcysteine for acetaminophen overdose?

The recommended dose of Acetylcysteine for acetaminophen overdose is 140 mg/kg, with a maximum dose of 17,500 mg. This dose is usually given as an initial loading dose followed by a maintenance dose over the course of 20 hours.

What are the side effects of Acetylcysteine?

The most common side effect of Acetylcysteine is nausea and vomiting. Other possible side effects include stomach pain, diarrhea, and rash. In rare cases, severe allergic reactions may occur. It is important to seek medical attention if you experience any serious side effects.

Can Acetylcysteine be used to prevent liver damage from acetaminophen overdose?

Yes, Acetylcysteine is the standard treatment for preventing liver damage from acetaminophen overdose. It is most effective when given within 8-10 hours after an overdose, but can still be beneficial if given up to 24 hours after an overdose.

Is it safe to take high doses of Acetaminophen/Paracetamol with Acetylcysteine?

No, it is not safe to take high doses of Acetaminophen/Paracetamol with Acetylcysteine. Acetaminophen overdose is the most common cause of acute liver failure in the United States, and taking high doses of both medications can increase the risk of liver damage. Always follow the recommended dosages and consult a doctor before taking any medication.

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