Metronadizole (Flagyl, "metro") is genotoxic and potentially carcinogenic

ldg

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Is your kitty on metronadizole? (Flagyl). This is not intended to scare people. But it's important information that needs to be carefully considered. Metronadizole (flagyl) is potentially carcinogenic both to humans and cats. It is to mice. From a 2009 study in cats:

Metronidazole kills target organisms by inducing formation of reactive intermediates within these organisms, resulting in disruption of DNA. 9 This disruptive effect is not restricted to microorganisms, and both carcinogenic and mutagenic effects have been documented in experimental animals 10 and metronidazole disrupts DNA in human blood lymphocytes. 11,13 The importance of these disruptions is unclear in humans - damage was not evident within 6 days of discontinuation of the drug. No information about genotoxicity in cats is available.

The study, "Single-dose pharmacokinetics and genotoxicity of metronidazole in cats" (Sekis et al. 2009. Journal of Feline Medicine and Surgery (2009) 11, 60-68) found

Genotoxicity, as measured by DNA disruption in PBMC obtained from cats administered metronidazole for 7 days and a feline lymphocyte cell line incubated with metronidazole, was observed in all cats and all lymphocyte experiments. This is similar to observations in people treated with metronidazole.11,13 The DNA damage resolved within 6 days of discontinuing metronidazole, also similar to findings in humans, 11,12 suggesting that DNA repair mechanisms correct the disruption induced by metronidazole. However, experimental studies in rodents have demonstrated both carcinogenic and mutagenic effects of metronidazole.10 Lymphoma is the most common hematological neoplasia in cats 26 and cats have a propensity to develop intestinal T-cell lymphoma. 27 It is interesting to speculate that chronic metronidazole therapy may damage lymphoid DNA, which, if unable to be effectively repaired by a defective repair system, could result in development of lymphoma. This may be particularly relevant to cats receiving chronic metronidazole to treat inflammatory bowel disease. Currently, no evidence exists that chronic metronidazole therapy results in lymphoma formation in cats, and additional associative studies are needed to show a correlation between chronic metronidazole exposure and subsequent development of lymphoma.

Bold, my emphasis.

Importantly, when used for 7 days, the DNA damage resolved in 6 days. So if needed for treatment of giardia, short term use is likely fine. But so many vets throw metro at just about any diarrhea, and many IBD kitties are put on it for long lengths of time. :( It is something that should be discussed with the vet in terms of risks vs. rewards, IMO.


Link to abstract at NIH: http://www.ncbi.nlm.nih.gov/pubmed/19155181

Link to full study, PDF: http://www.google.com/url?sa=t&rct=...IAtANP6EPGfUDTTNRQcH04Q&bvm=bv.59026428,d.cWc

(Sorry, can't get a direct link).



Also of note is a 2002 study, "Is metronadizole carcinogenic?" Bendesky et al., Mutation Research 511 (2002) 133–144

http://www.ncbi.nlm.nih.gov/pubmed/12052431

There is sufficient evidence to consider MTZ as an animal carcinogen. In this regard, the IARC has classified MTZ as an animal carcinogen. Germany has already prohibited MTZ for veterinary use while further studies are being carried out [68].
 

scarlett 001

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Well you have scared me.

Rexy has so many issues, and we have put her on a course of this antibiotic. Her issues are potentially life-threatening (it is not like we have used it for chronic conditions, this is her first time on it) and so it may be that in her case, the possible benefits outweigh the risks. Time to do some more homework. Sigh.   
 
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ldg

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:hugs: Honestly, if the feral kitties get Giardia, they're getting metro. I personally will use it for short term, specific problems.
 

scarlett 001

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Well, this is supposed to be a one-time treatment (no vet said that it would be ongoing). The course is supposed to be 3 weeks. I just looked into it, and the dosage is at the lower end of recommended dosages for cats so it is not a very high dosage. The range of dosage for a cat her weight is stated to be 35 to 160 mg either 1x or 2x daily and she is way at the lower end of this. So not an alarmingly high dosage. Not sure if 3 weeks is a normal dosage for her condition. It was an emergency vet who prescribed this.

It is thought that given her inflammation in bile ducts, liver and so on and so forth (her ultrasound was quite the complex mess of inflammation and distension and thickening all over the place), that there could be a bacterial component and that this is the best drug to get at that.

I wonder if the mice were given "regular" dosages or were given intentionally high dosages of the drug. Will take a look at the articles.
 
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goholistic

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Thank you so much for posting this, LDG! Sebastian has been on metro for a few months for his chronic pancreatitis and suspected IBD.  
  In general, he's doing pretty well. I've been wanting to take him off the metro, but was hoping to find a natural "replacement" with similar antibacterial and anti-inflammatory properties. Now what do I do?! I will definitely be printing out this study for my vet. In fact, I think I'll fax it over to the doctor right now.

 

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Oh wow, thank you for posting this. Sparrow's not on it regularly and hasn't needed it for almost two years now, but whenever she has a really bad diarrhea flare-up, her vet puts her on it. Next time it happens, I'll see what else we can try first.
 

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Patches has been on it several times before he went on a steroid.  He has had 2 mild flares in the last 3 years and both times he was given metro.  It seems like every time something works well there is a problem found with it.  
 

goholistic

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Thank you so much for posting this, LDG! Sebastian has been on metro for a few months for his chronic pancreatitis and suspected IBD.  
  In general, he's doing pretty well. I've been wanting to take him off the metro, but was hoping to find a natural "replacement" with similar antibacterial and anti-inflammatory properties. Now what do I do?! I will definitely be printing out this study for my vet. In fact, I think I'll fax it over to the doctor right now.

In doing some research on metro dosages, Sebastian's dose is pretty low. He gets 1/8 of a 250 mg tablet, twice daily, which is 62.5 mg a day. This makes me feel a little better only because it is lower than the standard. I wonder if we can bring it down to 1/16 of a tablet, twice daily, and see how he does. I've gotten really good at cutting the pills, but I think 1/16 is the smallest I can go! 


I've put on my research cap and tried desperately to search for a natural alternative to metro. The only thing that came up (in a forum thread about giardia in dogs) was coconut oil. Sebastian already gets a little coconut oil daily. I could try to increase this.
 

goholistic

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It seems like every time something works well there is a problem found with it.  
I think this is true with almost anything. You've seen the commercials for human prescriptions meds. I'm floored by all the side effects that the voiceover is reading off, with "death" oftentimes being one of them! Like LDG said, I guess it's all about weighing the benefits with the risks. 
  Except it seems many times pet parents are uninformed of the risks.
 

scarlett 001

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In doing some research on metro dosages, Sebastian's dose is pretty low. He gets 1/8 of a 250 mg tablet, twice daily, which is 62.5 mg a day. This makes me feel a little better only because it is lower than the standard. I wonder if we can bring it down to 1/16 of a tablet, twice daily, and see how he does. I've gotten really good at cutting the pills, but I think 1/16 is the smallest I can go! 
I did the math for Rexy's dosage and she is 65 mg or so a day (divided into 2 doses) so similar to your kitty's dosage. This too is at the lower range of things. Rexy is on the compounded liquid and luckily she takes it rather well - no foaming/frothing etc.
 

denice

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Patches has never been given Metro long term.  It's always been either a 5 day or 10 day course.  
 

scarlett 001

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I think this is true with almost anything. You've seen the commercials for human prescriptions meds. I'm floored by all the side effects that the voiceover is reading off, with "death" oftentimes being one of them! Like LDG said, I guess it's all about weighing the benefits with the risks. 
  Except it seems many times pet parents are uninformed of the risks.
I agree with the benefits vs. risks. Rexy is senior (15 yrs) with a mess of inflammation problems in the areas which this drug targets. Since being on this drug (plus the Vit B12 shot), I've seen a very notable and real improvement in her happiness. I think in her case, having a solid course of the antibiotic is worth the risk. A blocked bile duct will kill her a whole lot more likely if I don't deal with it vs. the small chance of a lymphoma developing because of the drug.

They often do tend to test the drugs at ridiculously high dosages, so it might be the case for this research. I work at a university and can access the complete articles for free, so when I have time I will read through these articles and report back any info that I can find out. This does not mean the drug is safe at low dosages, but it gives me more info to work with if I know the testing protocol and then I can weight the risks and such.
 

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Metro is a very hard drug as it has so many benefits but can have some serious consequences.  In working for a vet for 20+ years I have only seen serious reactions to this drug a handful of times.  Mostly it was neurological symptoms that we saw with it.  I can't really say if I have seen cancer or not as I know animals who have been on it in their lifetime have developed cancer, but who's to say they wouldn't have developed it anyways?
 

happybird

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I think this is true with almost anything. You've seen the commercials for human prescriptions meds. I'm floored by all the side effects that the voiceover is reading off, with "death" oftentimes being one of them!
My favorite was the one for an IBS drug (can't remember the name) with side effects including diarrhea with fainting. Really? Sure enough, it was eventually pulled. But the commercial was on for at least a year. (Sorry for being off topic)
 

goholistic

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I can't really say if I have seen cancer or not as I know animals who have been on it in their lifetime have developed cancer, but who's to say they wouldn't have developed it anyways?
Perhaps that is the question at hand. Are all these kitties with GI issues being prescribed metro more susceptible to developing lymphoma because of being on the metro? Does metro accelerate the morph from IBD to lymphoma?  (rhetorical question)
 

denice

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It could be part of it.  I think the most important thing to avoid IBD turning into intestinal inflammation is controlling the inflammation.  I didn't even know that people were using metro long term until I started seeing it here.  I remember recently someone, I think it was betsygee, adopted an IBD kitty that had been on metro for a very long time.  I think she has him weened off of it now.  It seems like when treating IBD there is a tendency to think of metro as an anti-inflammatory rather than an antibiotic with anti-inflammatory properties.

When medication is needed I think the right steroid at a minimal dosage is the better choice.  Of course long term use of any medication carries risk but I think the risk is much lower than what would come with the long term use of an antibiotic.  A lot of people, vets and pet owners alike, seem to have an issue with the use of steroids long term.  I know I wish Patches wasn't on a steroid but I think the risk that comes with the steroid is lower than the risk of the inflammation continuing.  He has tolerated the steroid very well though and hasn't developed diabetes so far.  I am sure that colors my opinion.

Patches two mild flares have been in the spring so I am sure it is from the extra hair he is swallowing.  I am going to try some things to avoid it this spring. I am definitely going to try the Miralax daily through the spring.  Before Patches was diagnosed I thought hair had something to do with it and I was keeping my other kitty in a lion cut to try to help.  Patches still got sick so I quit.  I may get Alice another lion cut in early spring.  She has long hair with a very thick undercoat.  If Patches still starts to get sick though I will go ahead and give him the metro.  I think a short course of metro is better than him getting another full blown flair with the inflammation.
 

scarlett 001

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When we talk about long-term use of this drug, what are we talking about? Months? Years?

Rexy was supposed to be on a 3-week course of the drug to ensure no infection in her bile duct and associated areas (and it has the plus that it has some anti-inflammatory properties). But for inflammation she is on steroids.
 

denice

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I don't consider 3 weeks long term, it's a little longer than the usual dosing but it's not long term.  If I remember right the kitty another member had adopted had been on it for 1 or 2 years.  
 
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ldg

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Well, a little bit of research reveals that panacur is the drug of choice for giardia these days. Apparently most strains of giardia have become resistant to metro anyway! I used metro for two of the feral kitties... last year? the year before? and it cleared up the problem. But I'll use panacur if needed in the future.
 
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