Thursday, February 09, 2006

Acetylcysteine for IPF

S.F. poses the following:

I tried to prescribe acetylcysteine for pulmonary fibrosis, based on the recent article suggesting some benefit. I was called by the pharmacist who had never heard of it in PO form. The article by Demedts in NEJM 11/2005 used 600 mg PO tid. If the average pharmacist is unable to find any info about the drug, it makes me wonder what to do next. Has anyone been able to find a pharmacist who is familiar with this rare and magical medicine? I didn't know PO was such a strange route. Isn't that what we give for acetaminophen overdose?

16 comments - CLICK HERE to read & add your own!:

Baleeiro said...

It seems that it can be found in nutritional stores as PO tabs. GNC has some formulation mixed with their Healthy Joints" combo. I have even found a site dediacted just to NAC: http://www.acetylcysteine.org/

Jeff H said...

Yes, oral NAC is available over the counter. I think it's critical to point out that in the recent NEJM paper, NAC was used IN ADDITION to Azathioprine and Prednisone. There are no trials that have evaluated NAC as monotherapy. Moreover, there was no "placebo" group included in the NEJM paper. So, there are NO DATA that oral NAC, as monotherapy, is any better (or worse) than nothing.

All we can conclude from the recent paper is that patients receiving Azathioprine and Prednisone, along with oral NAC, had decreased rate of decline in pulmonary function than patients receiving Azathioprine and Prednisone without NAC. Whether this is due to a beneficial effect of NAC or a potentially harmful effect of Pred/Azathioprine is not known.

Jennings said...

Well, since prednisone and azathioprine were given to both groups, and the group with NAC improved (with VC), then it would be difficult to hold to the view that the effect was due to the harmful effect of pred/aza since both groups got that. The only (apparent) difference between groups was the presence or absence of NAC.
As an example, we can't say whether 6 cc/kg is best or whether 12 cc/kg is harmful because those are the only 2 groups in that ARDS trial.

Jennings said...

But I see your point if we assume that prednisone is harmful - which is conceivable since it may even be pro-fibrotic as you know better than I. But nonetheless there are no studies comparing pred/aza to placebo so we really don't know...
I'm not sure if it is unreasonable to extrapolate from that paper and go with monotherapy based on the minimal side effects and the lack of any effective therapy for IPF.

Jeff H said...

It's only unreasonable to the extent that nobody knows the answer because the study has never been done. It's a shame that the placebo-controlled trial was never done with Azathioprine/Prednisone. I don't know if NAC has any benefit, and I doubt we'll never know. As it stands now, anyone who has access to the the internet can go to a health-food store, and take NAC, regardless of "other" therapy. As this is an OTC med, no true "placebo" controlled trial will be done.

Besides, the "benefit" from the addition of NAC was really quite modest, at best.

Jeff H said...

Besides, I think the recent NEJM paper on glucose control demonstrates the potential danger of "extrapolating" the findings of a trial...a single center study in a predominantly post-CABG population shows a benefit, and all of a sudden every ICU in the country is implementing an "intensive insulin" protocol. Now, we see that intensive insulin may actually INCREASE mortality in a group of medical ICU patients.

In both cases, the answer is: don't extrapolate, don't generalize. Assess the data, and if the study has not been done, either do the study or recognize that decisions are being made without data to back it up. That's ok--just know the difference between acting based on data and acting based on our best guess.

Arenberg said...

Jeff, read the accompanying editorial with the NEJM paper. It is conceivable that NAC just protects from some of the alleged adverse effects of Aza/Pred. This was a hypoithesis generatig finding, and interesting at that.

And yes. Most pharmacists have no clue how to provide NAC. The 600 mg tables are best found at health food stores (GNC Nutrition for example). Here is a link to cut & paste

http://www.drugstore.com/products/prod.asp?pid=41790&catid=11452&aid=335933&aparam=gnc_nac_600_600mg_capsule

Jennings said...

Let me push this 1 step further based on Doug's comments then:
If we are to believe that the NAC was beneficial because it protected against the harmful effects of the pred/aza, then we should be viewing pred/aza as a contraindication for pulmonary fibrosis, as opposed to simply thinking that it does not work. All of the IPF patients should be instructed to avoid these medications unless absolutley necessary for other conditions. If we do NOT want to interpret the data to mean that they should be contraindicated in IPF, then it must logically be concluded that NAC is beneficial.
If there is a 3rd interpretation, I'm all ears...

Jeff H said...

The third interpretation is that we should interpret the results for what they are. We do not know if Aza/Pred is truely harmful, because the study has never been done. We do not know if NAC monotherapy is beneficial, because the study has not been done.

All that we know now is that IF one chooses to give an IPF patient Azathioprine and Prednisone, THEN one should probably give the NAC as well. Everything else is simply guesswork and inference.

It remains possible, for example that one subgroup of patients may benefit from NAC, while another subgroup may be harmed by Aza/Pred. Previous small studies have suggested that patients improve with Aza/Pred ( Am Rev Respir Dis. 1991 Aug;144(2):291-6.). So, while the argument that either NAC is beneficial or Pred/Aza is harmful may be "logical" it is unproven and an oversimplification of the incredibly complex interactions that occur in a very heterogeneous disease population.

Arenberg said...

Read the editorial. Gary Hunninghake may know what he is talking about...

NEJM Volume 353:2285-2287 November 24, 2005
"What can we conclude from the study by Demedts et al.? One obvious conclusion is that acetylcysteine is directly beneficial as a therapy for IPF. However, another conclusion should also be considered. It is possible that the combination of prednisone and azathioprine is toxic to patients with IPF. If this were true, then it would be likely that the effects of acetylcysteine in this study are explained by the drug's prevention of the toxic effects of prednisone and azathioprine. It is known that azathioprine depletes liver tissue of glutathione and that acetylcysteine can, in some settings, prevent liver injury. In support of the latter hypothesis is the observation in the study by Demedts et al. that there were fewer myelotoxic effects in the group of patients with IPF who received acetylcysteine. Thus, it is not clear from this study whether the drug has direct beneficial effects on IPF or whether it prevents the toxic effects of prednisone and azathioprine. Therefore, a prospective study comparing prednisone and azathioprine with placebo is needed to address this issue. If a new study showed toxic effects or no effect of prednisone and azathioprine, investigators conducting studies of new therapies for IPF would be liberated from the use of this "standard of therapy," and patients would be freed from exposure to these potentially toxic drugs."

jgiustino said...

All I can say is that this was a bad study! The data from patients that actually completed the study did not show ANY signficant change in lung function between the two groups. The authors then needed to resort to "last observation carry forward" to show significance ....this is a highly controversial statistical method. I am very surprised that this has not been questioned by more people. I think that this study proved that NAC prevent bone marrow toxicity from imuran (they did not need "last observation carry forward" to prove this. All else is very suspect as far as I'm concerned and I wish they had the forsight to get a larger patient population into the study so they would not have to resort to such statistical games.

Anonymous said...

Let me chime in as a 49 year old male with lung fibrosis as a result of a case of PAP I had in my early 20's. The diease went in to remission, but after a bout of pneumonia seven years ago, I started to get bronchitis twice a year. Every time I got on a plane in the winter, it seems.

I developed traction bronchiectasis as well, and currently have about 60% lung capacity, and am being seen at Johns Hopkins, although only once a year since my health is otherwise great.

Two years ago, after researching endlessly on my own, I started getting pharmaceutical NAC from Germany through the New York Buyers club. Effervescent, 600 mg, twice daily. I have now only had one mild case of bronchitis in the past two years, and other than that, have not even had a cold. I feel better than I have in years. Anecdotal? Maybe, but my doctor, the Head of Pulmonary medicine at JH, is now impressed. They have been prescribing NAC in Europe for 30 years. I won't take the health store variety, and the other cost me a mere $1 a day.

Anonymous said...

NAC is extremely good medicine. For anything lung related but MANY other things as well.

Anyone who hasn't already, do a search on PubMed for n-acetylcysteine

I can post a VERY long list of refs if people want.

What is the procedure for patients asking questions here? Is it permitted? (I'm one who is trying to figure out what is making me sick)

You can buy bulk NAC but its quite inexpensive now and increasingly available in vitamin stores.

I've heard that many people with lung diseases have also had luck with nebulized NAC - emphysema, aspergillosis, etc.
(it also has some antifungal activity I've read)

Anonymous said...

I found a site to get pharmaceutical grade NAC from Germany. That health food store stuff is too inconsistent. The last poster was correct, it works on a HUGE list of ailments, all with real science backing it up. Check it out:

http://healthierlungs.com/

Anonymous said...

Check an informative thread here:

http://groups.google.com/group/sci.life-extension/browse_thread/thread/4131400ff612cc0d?hl=en#

Anonymous said...

I recently received a 70 page ad for a product that is based on a "Mayo Clinic Breakthru " A company called NutriHealth Supplements has an OTC product that contains NAC (exact dosage not listed )and 4 types of probiotics. Their claim is that this product is "guaranteed" to clear up all kinds of sinus congestion problems and end post nasal drip. I am considering buying
this product because I have been suffering sinus problems for 2 months. I also am diagnosed with IPF. Who knows it might help that too!? Their # is 1-800-914-6311. Product is called FloraSinus.