You are likely aware that there is a shortage of Interceptor and Sentinel right now. I have had several comments on my post about the Novartis shortages from people who are upset because they have a breed of dog who is sensitive to ivermectin and they feel that Interceptor and Sentinel are the only drugs that are safe to use for heartworm prevention for their dogs. I wanted to write a post to explain why this is not true.
The main concern is that some breeds of dog can have a mutation in a gene called MDR1. Dogs who have this mutation can be extremely sensitive to ivermectin which is the main ingredient in Heartgard. (What you may not know is that these dogs are also sensitive to the ingredient milbemycin which is the main ingredient in Interceptor and Sentinel. – More info on this later in the article.)
Dog breeds that are believed to be more likely to be carrying this gene include:
If a dog with the MDR1 gene mutation receives a high enough dose of ivermectin (or milbemycin) they can have serious neurological side effects including tremors, seizures, coma and even death. For this reason, if a vet feels that it is necessary to treat an animal with a significant dose of ivermectin (such as for treatment for sarcoptic mange) they will often recommend testing the dog for the MDR1 gene, especially if the dog is a herding breed.
The key to remember here is the dosage. Dogs who are sensitive to ivermectin can be negatively affected if they receive a dose of 50-100 micograms per kilogram. The amount of ivermectin that is in a dose of Heartgard is 6-12 micograms per kilogram and is not at all toxic to dogs even if they are carrying the MDR1 gene mutation.
For milbemycin, dogs with the MDR1 gene mutation can see neurological side effects at a dose of about 90 micograms per kilogram. Interceptor and sentinel usually delivers about 7-10 micograms per kg of milbemycin to the dog.
Both drugs are very safe to give to any dog as long as we give the recommended dosage.
It is possible that this belief has stemmed from good marketing. When Interceptor first hit the market, the packaging proclaimed, “Safe for ivermectin sensitive collies.” This implied that products like Heartgard that did contain small levels of ivermectin were not safe. But, in reality, both products contained small enough doses to be considered extremely safe even in dogs with the defective gene.
Yes, I do. I have no problem with a collie breed or any other breed with a potential MDR1 gene mutation receiving Heartgard. When it is available, I do prescribe more Interceptor than Heartgard, simply because Interceptor will also be effective against whipworms. But, as far as heartworm prevention goes, both products are very good.
As always, the goal of my website is to try and clear up areas of confusion that exist on the internet. Has this article helped, or do you have more questions? Leave a comment below and hopefully I can help clear up the subject even more.
Do you carry Trifexis or is this a cost savings like Banfield clinics and you only stock one product? I find it odd that you chance your client’ s dogs’ lives without erring on the safe side and doing the MDR1 test first. Could you send me the cites or at least publish the independent research that backs up your statement that collies and other breeds ( including Samoyeds) are just as sensitive to Interceptor? Unless you can back up this statement with multiple studies, it should be retracted. Playing Russian roulette with someone’s pet is irresponsible. Too many collies have passed because of just such poor advice.
Hi Susan. As mentioned in the article, dogs who have the MDR1 gene problem are sensitive to ivermectin at a high enough dose. There is no point testing a dog for MDR1 sensitivity just to put them on Heartgard which is a very small dose of ivermectin.
Here are some studies:
Ivermectin Toxicity in 17 Collies – This study was published in the Journal of Veterinary Internal Medicine and inside the article they state that “A dose of 50–60 ug/kg ivermectin was found to be safe in Collies known to be susceptible to the drug.” Once again, as mentioned in my article, the dose of ivermectin in Heartgard is 6 ug/kg.
Assessment of toxicosis induced by high-dose administration of milbemycin oxime in collies. – This study was published in the American Journal of Veterinary Research and states that “We conclude that ivermectin and milbemycin commercial formulations have similar margins of safety and that milbemycin toxicosis appears to be dose-dependent in Collies with a demonstrated sensitivity to ivermectin.” Yes, this is looking at milbemycin, but they also concluded that ivermectin is safe in the recommended doses for heartworm prevention.
Effects of dermal application of 10.0% imidacloprid-0.08% ivermectin in ivermectin-sensitive Collies – This study, published in the American Journal of Veterinary Research gave ivermectin to collies known to have the MRD1 gene. They gave 3-5x the dosage of ivermectin recommended to be safe (along with imidacloprid) and here are their conclusions: “Analysis of results of this study indicates that dermal application of 10.0% imidacloprid-0.08% ivermectin is safe for use in ivermectin-sensitive Collies at dose rates of 3 or 5 times the proposed maximum therapeutic dose.”
Canine ABCB1 and macrocyclic lactones: Heartworm prevention and pharmacogenetics – This study in the Journal called Veterinary Parasitology states that “all FDA-approved heartworm preventive products marketed in the United States are safe, even for dogs with the ABCB1 [MRD1] mutant/mutant genotype.”
And yes, in my practice I carry Trifexis, Advantage Multi, Revolution, Interceptor and Sentinel (when available) as well as Heartgard.
Now it’s your turn. You mentioned that “too many collies have passed because of just such poor advice.” If you have documented scientific evidence (not just anecdotal) of a collie dying after receiving Heartgard then please share!
Thank You very much for the information. I gave my Boarder Collie Heartgard twice with no reaction before my vet told me to use Interceptor, something about white feet do not treat. I was concerned when I couldn’t get Interceptor and had a good suppy of heartgard from a pet that passed. I found your site trying to figure out what to do. Thank You Very Much Milo
For all the “studies will show” I have direct experience to the contrary. I have two shelties who have always got interceptor with absolutely no side-effects. When my vet ran out of interceptor I switched to Iverhart – the generic equivalent to Hartgard. One of my shelties had a siezure the evening after I gave it to her. Scared me big time. She is fine now and I managed to scare up some smaller does interceptor to double up on for her. I pray I don’t run out before it is available again. My other sheltie vomited about an hour after giving it to her. I changed my aproach this month, chopped into small peices and fed about 1 hour after her morning meal. She did not vomit but had terrible diarrhea for a day. I can’t wait to get them back on interceptor again.
I don’t know if my dogs have “the gene”. They are from completely different sheltie lines, different breeders, different colors. But I can say that interceptor never caused any problems.
If you are saying that Heart Gard is just as safe for
Collies, then why is it that it is safe to give daily doses
Of Interceptor to a collie with generalized Demodex,
But not Heart Gard?
Interesting question. There are a few variables here. The reason why we use Interceptor and not Heartgard for treatment of Demodex is that the active ingredient in interceptor (milbemycin) was shown to be effective against demodex. (Here is the research study). Heartgard contains Ivermectin and although we can use daily ivermectin for treatment of demodex we would simply use the drug ivermectin rather than use Heartgard. It’s much cheaper to do it that way. Ivermectin on its own is widely available as a cattle dewormer. We don’t have milbemycin as an individual drug other than using Interceptor.
However, with all that being said, I would still have caution in using daily interceptor in a collie. The dose of milbemycin that is recommended to treat demodex is 0.5-1.6mg/kg. This converts to 500-1600 micograms per kg. For “normal” dogs this is generally ok. But, for a dog with the MDR1 gene this is well above the toxic dose of 50-100 micograms per kg.
There are two situations where I would feel safe using daily Interceptor to treat demodex in a collie. The first would be if the collie had been tested for the MDR1 gene and was found not to have it. (Not all collies have the problem.) The second would be what we did before testing was available. If we really wanted to put a potentially sensitive dog on either ivermectin or milbemycin at high doses we would start off with extremely small doses, very gradually increase the amount and look for mild side effects. If there were any neurological issues at all then we would discontinue the drug.
Hopefully that makes sense!
My Standard Poodle was given the correct dose of Interceptor and had the same irreversible neurological reaction leaving him so completely disabled that he could not eat, stand or walk. After fighting for his life for several weeks, I had to let him go gently and peacefully. I will NEVER use this wormer again. Why take any chances with your family member when there are “safe” tried and true alternatives. R.I.P. my beautiful boy Ziggy ~
Nationl Geographics did an article on a number of breeds showing their DNA ancestory. Much to our suprise, Borzoi were classified as a herding dog and much closer genetically than some other Sighthounds! Then again we were not suprised because we know they are as suseptable to the same drugs as Collies with the MDR1 gene. It is about time this breed was included with the MDR1 dogs. Being a breed with fewer numbers it is not likely they will be given a study. It is not financially feasable to study. Meanwhile they too continue to die from various drugs, not just Ivermectin. I also would like to ask why a dermatological test was done with the dewormer rather than testing to see if once in the blood, it passed the brain barrier! ……and how much remained there ie accumulative effect of Ivermectin product.
Thank you for this information. It helps to understand why one vet is saying “White Feet, don’t treat” and another is saying Heartguard is fine.
“White Feet Don’t Treat” is what I was taught in school for when we were trying to decide whether ivermectin injections were safe for an animal. This was before we had MRD1 testing available…it was better to be safe than sorry. Many herding dogs who could have the MRD1 issue have white feet. But, again, it’s all about dosage. I have never had hesitation about giving a collie dog (or a white footed dog) any heartworm meds. But I would think twice before doing high dose ivermectin (i.e. for treating for demodex for example.)
As regards Heartgard and Australian Shepherds….I had been giving Scarlett Trifexis until the tick season appeared. The vet recommended Certifect and Heartgard. Since this time, we have noted that she develops serious diarrhea following dosage. I worry that I am poisoning her! From what I read in your blog, it isn’t clear whether there is any correlation. Scarlett is 6 1/2 years old, active, spends 1/2 of her day outdoors in an open area with woods. But lately she is being a bit sluggish. We know she is middle aged, however her exhaustion following a busy frisbee/tunnel exercise is concerning. Any advice you can give?
I greatly appreciate finding this article today, as we are investigating our German Shepherd mix dog’s seizures which began only 3 months ago. The seizures come in clusters of 4 within a 24-hr period, about 1-2 months apart (so, yes, that means only 3 clusters have occurred so far) While we currently have our hands full dealing with Pb intolerance on a massive scale, which was undetected by our first vet, we are also investigating whether a switch from Interceptor to Ivermectim could have triggered the seizures, as 2 of the 3 clusters occured within 24 hours of the first and second dose ever of Ivermectin. The information you provide here will be a help as we determine whether the seizures are chronic or triggered, as well as what heartworm preventitive is safe.
thank you for your expertise regarding heartgard for shelties. i feel a lot better now.
your product Trifexis has resulted in neurological problems in my collie she is so bad has to be put to sleep it is criminal that you promote this product while pets are dying and their owners broken hearted
I have a tri rough Collie and took her into the vet’s when I got her at 12weeks. The vet was supposed to be “experienced” with rough collies. I was concerned about MDR1 since the sire/father had the gene. The vet gave me a flea medicine I’d never heard of and said it didn’t have invermectin and “was safe for collies.” Two hours after applying the topical treatment she vomited. The problem was that I didn’t have a box with the ingrediants listed. The vet gave me a single dose which was a tube. When I called and bitched them out…they all swore it did not have invermectin. I use interceptor for heartworm but have not tried another flea med. I use dawn dishsoap or apple cider/water mix to prevent fleas. I have been considering Sentinel but am so scared.
Thank you for all the detailed information. It is so hard to loose a pet and we love them like family. We just have to use the information we have to make the best decisions we can. Unfortunately, nothing is perfect. I appreciate this web site and discussion.
Dear Dr. Marie: Our 8-yr-old Shih Tzu has always been on Heartgard Plus and Frontline Plus, but several months ago the Frontline just stopped working. Vet gave a new kind of Frontline Tri-something, used for 3 months but it didn’t kill the fleas at all. He’s allergic to flea bites so the vet gave him one dose of Comfortis 3 weeks ago. That killed the fleas, but now we are horrified to find he has tapeworms, the kind caused by swallowing a flea! Also, his hair is so sparse now that his skin shows through in places. This morning he got Drontel Plus and is to take another dose of that in 3 weeks for the tapeworms. He has been trembling for a few seconds every few minutes this afternoon, but otherwise seems OK. Vet also gave me one Trifexis pill to give in a week (because it hasn’t been a month yet since the Comfortis.) I’m afraid of these oral flea meds, and of the additional dose of worm meds in the Trifexis in between the two doses of Drontel Plus. (He did not have any other kind of worms.) But he can’t have fleas! What can we use instead of the oral flea meds? Frontline doesn’t work at all any more. I do NOT want to give him anything harmful to him. We love him so much. Also, Trifexis doesn’t treat for tapeworms. Should he get something for that periodically? Very worried. Thanks
Because of the shortage of H W preventative for Sheltie type my vet also recommended Hartgard.. I have used it today on both my dogs (just after the dogs eat thier breakfast) and both are fine and did great today. I did it over a weekend so I could keep an eye on them….Both of them do have one or more white feet….
Since Interceptor is unavailable, my vet recommended Trifexis. It has the same main ingredient as Interceptor with an added Flea Control. It smells like poison. My gut is telling me not to give it to my precious Sheltie. It has an INSECTICIDE in it. Is there not a product out there with just milbemycin oxime. I don’t have a flea problem.
I could go on and on about this subject. But the bottom line is when my Aussie/Blue Heeler mix took HeartGard, she went into shock twice (right around the age of 1&1/2 years old) and I almost lost her before we figured out it was the Heargard. She does have the MDR1 mutation. But we did not know that when her two shock episodes occurred. When she would go into shock, it was without warning. She would freeze and would not move. Her gums turned totally white and she got extremely lethargic. Her liver enzymes shot through the roof and her heart would race. It was absolutely horrible. I spent over $4000.00 on the two ER visits because they had to keep her for several days giving her IV fluids and watching her very closely. I am a pharmacist and did my own research. I told my vet I wanted her off Heartgard. He didn’t think that was the issue, but agreed to change her to Interceptor. She is now 5 years old and has not had another episode in 3.5 years. Maybe it is coincidence, but I will not be giving her anything with ivermectin. I do agree that they can also have a problem with Interceptor – however in my experience, Interceptor is the way to go. I have no doubt if I give my dog Heartgard, it will kill her – absolutely NO doubt. Just my experience.
You are a great vet.
My little Buddy has his chin on my neck as I lay here in bed reading all your comments. I have spent countless hours and dollars keeping him alive and it has been me feeding him what is killing him. I feel miserable! Sorry for those that have lost their loved ones but thank you for sharing. I dont know what I am going to do but it will not be giving him HearGuard or Trifexis. This story has been going on for two and a half years. Time to find another vet…fun fun.