Milbemycin Oxime toxicity in animals and dogs ( Sentinel ) - Page 1

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bubbabooboo

by bubbabooboo on 28 May 2016 - 13:05

Recently a post was made about a dog displaying signs of neurologic problems that had been on lifelong treatment with Milbemycin Oxime and Lufenuron ( Sentinel ).  I did some research and was concerned with what I found.  A link below to the general safety and toxicity of Milbemycin Oxime in animals and dogs.  It should also be noted that Milbemycin Oxime use in dogs can produce skin diseases and conditions and there is no antidote for Milbemycin Oxime poisoning.  Owners of dogs exhibiting neurologic or skin problems should be aware of these being linked to Milbemycin Oxime toxicity when using Sentinel.  Vomiting, stomach, and intestinal problems are also a concern but these may pass after a few days however the neurologic symptoms are much more difficult to diagnose and identify which is what the makers of Sentinel rely on.  In many of the product safety trials with Milbemycin Oxime the results were given as no adverse effects or toxicity reported .. which is a weasel way of saying there could have been effects but they could not be absolutely diagnosed as being related to the product.

http://parasitipedia.net/index.php?option=com_content&view=article&id=2673&Itemid=3005

A link to the original post

http://www.pedigreedatabase.com/german_shepherd_dog/community.read?post=866882-sigh-i-suspect-dmhow-to-know-for-sure-and-then-what

The dog discussed in the OP was showing neurologic problems with movement and vigor.  The dog was also being treated for skin problems using a cyclosporine ( immune depressant ) which is also used to treat Milbemycin Oxime toxicity in cases of overdose.

 

Milbemycin oxime is is the same chemical family ( macrocyclic lactones ) and has the same mode of action as Avermectin, Ivermectin, Moxidectin and others .... it just has a different sounding name.  You may better know macrocyclic lactones as the ai in ProHeart, Heartguard, Trifexis, and other treatments targeted for heartworm control in dogs and used in a variety of animals, however Milbemycin Oxime is only used in pets and unfortunately less is know about it's safety and toxicity as a result.  Milbemycin Oxime is only sold via prescription and this limits the reporting of adverse effects as vets seldom report adverse effects and the maker Novartis has shown no interest in addressing toxicity concerns .. telling vets and pet owners alike the adverse effects are coincidental or unrelated when reports come in.

 

WARNING: Dogs of some breeds are sensitive to milbemycin oxime, other macrocyclic lactones or other drugs (e.g. emodepside) that can cross the blood-brain barrier. They can suffer more or less serious adverse effects if treated at dose rates higher than the recommended ones. Consequently dosing must be as accurate as possible. This is the case for Collies and related breeds, which have a mutation in the MDR-1 gene that affects the blood-brain barrier and makes it more permeable to such compounds than in dogs without this mutation. Besides Collies, other dog breeds have shown similar problems, although the MDR-1 mutation has not been confirmed in all of them. The breeds more affected by this mutation are (% frequency): Collie (70%), Long-haired Whippet (65%), Australian Shepherd (50%, also mini),  McNab (30%), Silken Windhound (30%), English Shepherd (15%), Shetland Sheepdog (15%), English Shepherd (15%), German Shepherd (10%), Herding Breed Cross (10%). Other less affected breeds are: Old English Sheepdog, Border Collie, Berger Blanc Suisse, Bobtail, Wäller. The only way to be sure that a dog is affected or not by the MDR-1 gene defect is to test for it. As more dogs are tested it is likely that the mutation is discovered in other breeds, or that the frequencies change.


bubbabooboo

by bubbabooboo on 28 May 2016 - 14:05

Additionally .. symptoms of Ivermectin toxicity ( same chemistry ) include hind limb paralysis in cats and uncoordination in both dogs and cats. These symptoms could be misdiagnosed as DM in dogs.

http://vetmedicine.about.com/od/diseasesandconditions/a/CW-IvermectinSafety.htm

It is also worth noting that in the milbemycin oxime toxicity tests for dogs the breed of dog used was almost always beagles or unidentified ( low susceptibility to the toxicity of the product ) and these animals were usually kept confined to cages or small pens such that any observation of toxicity related to movement would be unnoticed unless the dog was severely affected.


Zenit2010

by Zenit2010 on 28 May 2016 - 16:05

I was researching much of the same information last night too, Bubba. It looks like I can send for a DNA test for the MDR-1 gene to see if my dog is in that 10% statistical category. Nonetheless, what do I do for heartworm and for fleas, assuming I keep him on Atopica.

I've had 4 dogs over the last 35 years in the same city in Southern California. I had a sheltie and a GSD together thru the 1980's and early 90's, then another GSD from 1997 to 2009, and now this GSD since 2010.

We used to fog the house in the 80's and 90's for fleas, spray pesticides outside, bathe the dogs in harsh shampoos and use flea powder, and feed them Purina Dog Chow. The sheltie lived to 15 1/2 and the GSD to 14 1/2. Oh, and no heartworm medicine, but, yes, booster vaccines every year.

Then 1997, we learned about Frontline for fleas. Yay, we thought, no more fogging the house and needing to spray outside. Vaccines were limited to every three years when rabies was due. We also started feeding higher quality food, but still no heartworm preventative. Our GSD was always suffering from fungal skin conditions and itchy paws. He lived to 12 1/2.

Now, my current dog... you and the forum already know that story from my other posts. These new drugs certainly add convenience to our daily lives, but they seem to be robbing our dogs of their long term health (at least in my case).

bubbabooboo

by bubbabooboo on 28 May 2016 - 19:05

Sentinel is not a good flea control treatment. The flea control in Sentinel is primarily from the other ingredient Lufenuron which does not kill fleas but prevents them from reproducing. If heart worms are not a concern then Milbemycin Oxime is not required in your dog's pest control program. To kill adult fleas Capstar (nitenpyram) is a very low toxicity choice but with short duration (24-48 hours) . Spinosad which is the ai in Comfortis ( requires prescription ) is also an option and if you give Comfortis on a 1/2 dose every three week schedule it is just as effective as a full dose given on a 30 day ( once per month ) schedule in published results from the manufacturers efficacy tests.  Comfortis (spinosad) gives rapid control of adult fleas and kills new ones as they hatch or reinfest your dog.  Obviously a 1/2 dose every three week schedule is safer as peak concentrations of the pesticide are roughly 1/2 of the full dose just with more frequent dosing.  From my experience with spinosad given on a three week schedule no additional flea control is needed.  If you prefer to continue with Lufenuron it is available as Program branded product and can be given in combination with 1/2 the normal dosing for Comfortis every three weeks.  For any dog giving less than the labeled dosage is legal however any manufacturer's warranty of efficacy or safety will be invalid ( and good luck with that anyway ).  Separate dosing of pesticides spread over more days is usually a good idea as it reduces peak load on the immune and animals body. Comfortis is an oral product and there have been reports of toxicity with spinosad when given at full dosage in combination with macrocyclic lactones such as moxidectin, milbemycin oxime, avermectin, and ivermectin. Trifexis ( a combination of spinosad and milbemycin oxime ) has had reported toxicity problems and there may be an interaction between spinosad and the macrocyclic lactones with regard to metabolism or inactivation ... best to avoid with your dog I suspect.  As our dogs age they may become more sensitive to pesticides so even though a pesticide was once seemingly tolerated by your dog when young and strong as their health declines the toxicity may become apparent. And there is also a school of thought that says the incessant dosing of our pets with pesticides and vaccines contributes to their decline in health and may hasten it.

https://en.wikipedia.org/wiki/Spinosad


bubbabooboo

by bubbabooboo on 30 May 2016 - 15:05

Milbemycin oxime ( Sentinel, Interceptor, and others ) has a label for use at 1/5 of the rate used in Sentinel for heart worm control only ( called SafeHeart ). The higher rates used in Sentinel are only for worming effects not for heart worm control which begs the question does an adult dog need worming once per month?? The registration for SafeHeart was granted but the product was never marketed .. likely due to the marketing department wanting to milk every last cent they could from the milbemycin oxime product.  These heart worm macrocyclic lactone products ( milbemycin oxime, moxidectin, Ivermectin, etc. ) are so inexpensive to manufacture that if the maker can sell 5X the dose needed for heart worm control for $2-$3 more per treatment as a wormer they make more money than selling the lower dosage.  The limiting factor in dogs and cats is toxicity not manufacturers cost in setting rates.  Milbemycin oxime is not sold as a wormer in farm animals at much higher rates but others of the same chemistry are and they are not given monthly.

http://www.fda.gov/AnimalVeterinary/Products/ApprovedAnimalDrugProducts/FOIADrugSummaries/ucm054862.htm

RECOMMENDED DOSAGES: SAFEHEART Tablets are given orally, once a month, at the recommended minimum dosage of 0.1 mg milbemycin oxime per kg of body weight (0.05 mg/lb). Recommended Dosage Schedule Body Weight Tablet Size 2 -50 lbs. One Tablet (2.3 mg) 50.1 - 125 lbs. One Tablet (5.75 mg)


Zenit2010

by Zenit2010 on 30 May 2016 - 16:05

Thank you for this research and information, Bubba! This helps a lot! I am going to make a change from Sentinel for my dog. It does look like heartworm is a concern now in our area because of the spread of mosquitos. Flea control is always necessary. Unfortunately, for my dog, Atopica is a necessary evil. But I can probably cut out a couple of doses per month and still keep his itchiness under control. His environmental allergies are severe and, without Atopica, his allergy symptoms were also hampering his quality of life.





 


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