# Any known problems with Xeno 450



## judyandhoney (Jan 27, 2010)

Hi all, 

One of my rabbits has recently died, around 18 hours after treatment with Xeno 450 (spot on treatment of Ivermectin by Genitrix). Both rabbits have been treated for mites at the same time, both came home within 5-10 minutes, started grooming themselves and each other, spreading the fluid to their bodies, head and ear, and no doubt ingesting the medication. The same evening, both rabbits seemed quiet and didn't want to eat anything. In the morning i got up to find one rabbit extremely bloated and cold, died at the vets a few hours later. 

The treatment with Xeno 450 may or may not be linked to my rabbits death, but I am trying to find any information of known effects/side effects/allergic reactions after treatment with Xeno 450 so that I can pass to manufacturer. Genitrix are not aware of any side effects of the medication (even if ingested) but are willing to consider any cases I can present. Has anybody ever had or heard of anything worth reporting? Does anyone have any information with regards to white rabbits being more susceptible to any side effects? 

Thank you for your help... I hope that, if there is a problem, it can be identified... and I hope it helps other bunnies...


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## Pipp (Jan 27, 2010)

So sorry. 

I had that (almost) happen with a cat, she survived but was never quite right after she licked a flea treatment on another cat. My Vet kept telling me it wasn't the cause, the treatment was safe, but that was misinformation. 

I did confirm that it can be deadly if consumed orally within the first hour or so after an application and saw the same info from somebody's rabbit vet about Xeno 450.

That's the reason it's applied to the back of the neck, it needs to be absorbed and the area dried before it makes contact orally.

With Xeno 450, it may be among the safest ones, but I was sure it came with a recommendation that two pets be separated for 24 hours -- definitely until it dries at least. 

The Vets, manufacturers and retailers should be making that far more clear. 

Odd that Genitrix isn't saying that.

Definitely worth more research and warnings. 

Really sorry you lost your bunny. 


sas :sad:


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## pamnock (Jan 27, 2010)

In rare cases, Ivermectin can cause side effects or be fatal (topical, injected, or ingested). There have been a few cases documented on RO.

The reaction can be due to an overdose or a gene mutation that allows the medication to cross the blood-brain barrier.

Side effects are generally neurological and may result in breathing depression/death. 

There is no antidote - supportive treatment is recommended. Some rabbits do recover.


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## Pipp (Jan 27, 2010)

Pam brings up a good point. What kind of rabbits were they or at least what kind of markings? 

I believe the dutch-marked bunnies were having more issues with Ivermetcin than others, weren't they? 

But I did read a reference from somebody's Vet that that particular medication is completely safe after 40 minutes, but before that it can cause a problem, GI related I do believe. (Still trying to find the original reference). 

In this case, the fact that the med was licked that soon and that both bunnies were 'off' that night tells me that the unabsorbed med was the most likely culprit. Very unlikely coincidence.

But genetics may play a role even when its not ingested, so that needs further study.


sas onder:


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## judyandhoney (Jan 27, 2010)

The rabbit that died was a white albino lop, 6.5 years old... the other one is a brown lop, around 7.5 years old, both with previous history of dental problems... I am very interested to find out specific cases/info about ingesting the drug and any problems it may cause... The role of genetics is certainly a very interesting one... thank you all for your comments... Pipp, can you point me to any specific info please?


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## pamnock (Jan 27, 2010)

Here is more info on the mutation (which many animals, including humans have). http://www.roughcolliebreedcouncil.org.uk/drug_sensitivity.html

The rabbit breeds that most sensitivity has been notedare the blue Dutch and blue eyed whites.



The drug can have a similar effect whether applied topically (absorbed through the skin), injected, or ingested.


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## ra7751 (Jan 27, 2010)

First, condolences on the loss of your rabbit.

I have used Ivermectin in all breeds of rabbits for many years prior to the release of Selemectin. And I used it on breeds that many claim they can't be used with....Albino and Blue Eyed Whites. Only reaction noted was a small skin issue at application point which is not uncommon. Ivermectin is technically an antibiotic and any individual can experience an adverse reaction. Ivermectin toxicity is normally presented as CNS depression. My thoughts would be an allergic reaction, overdose by oral ingestion (I have given Ivermectin orally but prefer transdermal or injection....and have used Ivermectin on very delicate cottontails that weighed less than 45g) or a possible reaction to death/decay of a large number of internal parasites that could result in anaphylaxis. This product is licensed and labeled for use in rabbits, guinea pigs and birds and dosing, as with any drug, is based on weight. It certainly wouldn't hurt to alert the company just for their benefit in the unlikely case their product is responsible.

Randy


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## pamnock (Jan 27, 2010)

Just to clarify,


I have never seen it stated anywherethat there areclaims ofbreeds that Ivermectin *can't* be used on. However, there are particular lines that *may* carry a genetic mutation that *may* make them more sensitive to the drug. Just as collies are more susceptable (so it is advised not to use the drug on collies). However, not all collies carry the mutation.

The MDR1 mutation has nothing to do with an allergic reaction, however, some animals are allergic to ivermectin.


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## tonyshuman (Jan 27, 2010)

I agree that it sounds like an allergic reaction/genetic mutation. Unfortunately it occurs occasionally, and is more common in some lines/breeds than others. No drug is free from these issues, although perhaps in the future, a drug that doesn't have as high a prevalence of issues (selamaectin might be one) might be a better choice for treating your bunnies. Unfortunately, we can't tell from looking at a bunny that it will or won't have an adverse reaction, unlike we can tell with some dogs (collies), so it is always a risk when using ivermectin on bunnies.


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## Pipp (Jan 27, 2010)

Randy, great point about the potential die-off of parasites affecting Judy's rabbits. I don't know about the mites, but if there were pinworms or something as well, this would account for both rabbits, seeing as they'd likely both be infected.

Or for all we know they may have eaten something that didn't mix well with the drug or they had been on another med. (Known interactions is a "No Data Available"). 

Judy, were they related and did they live together? Any sign of other parasites? Were they on other drugs? 

Another thing that popped up in my research (with no further data) was a brief mention in a Veterinary dermatology workshop on parasite medications for rodents and rabbits that said that dental (and eye) issues could affect the skin. More info there would be interesting.

Re: The genetics, there is a warning on the Xeno 450 packaging not to give it to dogs or other animals, "especially Collies and Old English Sheepdogs." I've been looking at some of the studies done on this drug with rabbits (which are few and far between) and it doesn't appear anybody so far has addressed the same genetic colouring in rabbits as in the Collies and Sheepdogs. 

I'm hoping that someone has or is trying to connect the dots somewhere, I keep thinking there must be hundreds of studies out there, but the truth still seems to be that for all the use of rabbits in human testing, nobody seems to bother testing rabbits for the rabbits' own benefit.  

What I'm seeing in fairly recent documents and workshops is that no data exists, which seems to be echoed by the company. "No data available." Obviously I can't access all the studies and Vet journals, but from what I have seen, nobody has done any kind of extensive testing on the oral ingestion of the spot-on drug much less the genetics. With the studies that have been done, the test groups are usually too small to catch what may be a one-in-a-thousand sensitivity. (After all, they're only rabbits). 

But Randy, to say that it's probably not true because its never happened to you after treating many rabbits is the same thing. If you have treated and documented thousands that have taken the spot drug orally (the issue at hand), and even 10 of them were blue dutches (the secondary genetic issue), I think that would be closer to the a sample used to determine safety in human studies. 

Sensitivities, genetic or not, exist with everything -- I can't eat certain brands of apples without getting gas. Touching tomatoes gives me eczema. One veggie will upset one bunny and no others. 

I find any blanket denials that the drug had something to do with the death to be totally untrustworthy. First off, you're dealing with a drug strong enough to require dire warnings about wearing gloves when adminstering it and safely disposing of the containers, and the drug is designed to kill living organisms. Its designed to be absorbed through the skin, not given orally. And we know rabbits have sensitive GI tracts. 

I think the existing tests with relatively small sample groups are proving Xeno 450 to be very safe, but I doubt they administered it orally to a lot of older lops with dental issues. 

When my cat had her reaction, I got the same absolute denials from the Vets and drug company, who told me that it looked like she had an allergic reaction, but it wasn't from the drug. :rollseyes They wanted to know what food she had been eating. ("Uh, she ate a spot-on flea med for dinner". If she could have a sensitivity to fish, she could have one to the meds. She ate the meds and got sick. I don't believe in coincidences. I'm going through the same thing with a cleaning product at the moment who have their corporate denials down to a better science than their product development). 

So yeah, its an uphill battle trying to prove this, but its great to pursue it, hopefully it will inspire more studies and more data. 

I've emailed a couple of Swedish Veterinarians at a University there who specialize in dermatology and parasitic issues who have done some testing on the drug on just over 50 random rabbits with no problems just to ask if any were dutch-marked (which doesn't really relate to Judy's issue) but I will contact them again with further questions if I get a response (other than 'whoareyougoaway').

Sorry I can't help with the documented case, I think the reference was just a Vet telling someone who's rabbit licked the Xeno 450 off another rabbit that it was completely absorbed after 40 minutes and the rabbit had no adverse reactions. (It was licked after it dried). And I don't think the 24 hour rule is issued for that drug like it is for Advantage, etc, although almost all others list the 'letting it dry' warning. Really don't understand why that's not the case for rabbits -- although it may be those small test numbers again. 

This may be a one-in-a-thousand case, but it can still save that next one-thousandth bunny. 


sas :expressionless:


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## judyandhoney (Jan 28, 2010)

Pipp, thank you so much for this exhausting post. Looks like what you have been through after your cats reaction compares largely to what I've been through and what I am trying to achieve. The problem is no data and small test samples before releasing the drug. "This may be a one-in-a-thousand case, but it can still save that next one-thousandth bunny. " Exactly my thoughts... Thanks


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## judyandhoney (Jan 28, 2010)

Forgot to say.. They were not on any medication at the time, they were both happy bunnies, eating hay and running like crazy around the house. They were not related. My white bunny was always the sensitive one tho, if there were troubles with anything, it would be always him.. Unless the other one is a tough one! Ah, I miss him so much!


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