Dogs on drugs: FDA warns of dangerous drug interaction

June 26, 2008

Dogs who are taking the flea preventive drug Comfortis (spinosad) at the same time they are being given high dosages of the drug ivermectin, such as those used in the treatment of demodetic mange, are at risk of ivermectin toxicity.

The maker of the drug, Eli Lilly’s companion animal health division, does not believe that there is any risk to using the regular heartworm-prevention dose of ivermectin with Comfortis; the daily dosages used to treat some stubborn cases of demodetic mange are as much as 100 times the monthly dosage used to prevent heartworm infection. In an informational release, the company cited a supporting field study that involved hundreds of dogs (PDF file):

The administration of Comfortis and approved canine formulations of ivermectin at doses labeled for heartworm prevention has been tested and shown to be safe, including in a North American field trial involving over 450 dogs that were required to be on monthly heartworm prevention throughout the three-month study. Laboratory work has found that, even at doses of 5 times the monthly dose of spinosad combined with 10 times the monthly dose of milbemycin oxime in ivermectin-sensitive collies, there were no signs of neurotoxicity (Sherman et al., publication pending).

The FDA Center for Veterinary Medicine is advising that the two drugs not be prescribed at the same time.

Ivermectin toxicity can be fatal and requires immediate veterinary care. Early signs include vomiting, weakness, drooling, tremors and coma. Dogs also often become blind, although this is usally reversible.

With aggressive veterinary care including hospitalization with round-the-clock nursing, most dogs will recover.

High-dose use of ivermectin is considered “extra-label,” which means a use of an approved drug to treat an illness for which it has not been approved. Such use is legal under the Animal Medicinal Drug Use Clarification Act of 1996; without extra-label prescribing, half or more of the drugs used in veterinary medicine every day would be unavailable, including most antibiotics.

Filed under: pets, connected — Christie Keith @ 5:36 pm


  1. Is this a problem only for dogs who have the MDR-1 mutation, or for all dogs?

    Comment by H. Houlahan — June 26, 2008 @ 6:59 pm

  2. All dogs. But I can’t help but think dogs with the MDR-1 mutation would be at greater risk. I believe there is a study underway to look at this issue more carefully now that this interaction has been identified.

    Comment by Christie Keith — June 26, 2008 @ 8:47 pm

  3. My first thought when I read this was that MANY people using “extra-label” Ivermectin for HW prevention are mistakenly using the mange dose which is a much higher dose than needed for HW prevention. I see this all the time on various boards. Granted, they are overdosing monthly – not daily – but OTOH they are unaware they are overdosing.

    Comment by slt — June 27, 2008 @ 4:00 am

  4. Agreed about the off-label ivomec. I can’t tell you the number of times that, when confronted with the math (here’s the dose in mcg per kg of Heartguard; here’s how you dilute the ivomec to get to that dose, or close to it, look I’ve shown my work), the guy who is giving his Sheltie a full ml of cattle ivomec every month will object that MY VET TOLD ME THIS IS THE DOSE.

    FWIW, I do the off-label ivomec, and don’t go through the bother of diluting with glycerol of propylene glycol. Every dog gets an overdose — one small drop of ivomec on a biscuit. But every dog I own has either been tested, or is known by parentage, to be MDR1 normal/normal. Including the German shepherd! I keep Heartguard on hand for the rescue fosters that come in with unknown pedigree for MDR1, or are known to be at risk for the mutation.

    If Heartguard wasn’t overpriced on such a robber-baron scale, the bottle of cattle wormer in the fridge wouldn’t be such an obvious solution for so many rural dog owners. I just wish they’d do the math instead of substituting the letters “DVM” for research, and I wish they’d get at least dogs from at risk breeds or suspect mixes tested for their mutation status.

    (I’m also a bad, bad, disobedient consumer, and buy the largest vials of Frontline from Australia, then carefully measure with an insulin syringe and split the doses between 2-3 smaller dogs. Cuts my tick control costs by well over half.)

    Comment by H. Houlahan — June 27, 2008 @ 7:20 am

  5. I do similar to what you do H and for the same reasons. And yes, have personally corresponded with (or seen on boards) several Vets who give the mange Ivomec dosage for HW prevention. Now some people are concerned that HWs are developing a resistance to Ivermectin and I wonder if that goes beyond the usual “parasites eventually develop resistance to drugs in widespread usage” and crosses into so many people overdosing their dogs as a contributing factor.

    Comment by slt — June 27, 2008 @ 7:35 am

  6. When I was visiting my rancher friend in Texas, we went to the feed store. (Yeah, party down in ranch country!)

    For the first time I saw Ivermectin in bottles face to face. (Our citified local feed store doesn’t carry it.) And I thought, as I always do, that it would be better for veterinarians to help their clients skip the brand name and protect their pet. ESPECIALLY in poor rural areas with bad heartworm problems, like where I was in Texas.

    Comment by Gina Spadafori — June 27, 2008 @ 8:16 am

  7. My dog Benny is taking Ivermectin for congenital parasites, he also received a dose of comfortis last night (both prescribed by vet). This morning Benny was panting, drooling, and ataxic, after an emergency visit to the vet I was told these meds should not be given together.

    Comment by Pam Goins — June 29, 2008 @ 12:23 pm

  8. I hope Benny recovers and is okay!

    You should report this as an “adverse event”. Here is a page on it:

    Comment by The OTHER Pat — June 29, 2008 @ 1:48 pm

  9. last month my mom gave my dog butters comfortis and heartgard and he kinda couldnt jump but he got better in a day or two, that was the first and only time we gave him comfortis this month my mom gave him his heartgard and he got really bad. we couldnt find a vet open and thought he would be ok. well he wasnt and it was the most horrifying thing i have ever seen i do not want to see my dog in that much pain

    Comment by Adriane — December 7, 2009 @ 10:42 am

  10. Just my two cents, but I will NEVER give Comfortis to a dog again. My 13-year-old dog (granted, she was 13, so the fact that all these problems developed just after she went on Comfortis could be a coincidence…but I personally do NOT think so) developed all sorts of odd problems after doing on Comfortis last summer. Within six months, she was dead. Prior to that, she was totally healthy. After going on Comfortis, she developed trigeminal neuropathy, a disease in which her massiter muscle just wasted away to nothing, leaving strange and alarming (to me, anyway) indentations in her head. This was the first truly alarming sign. She also developed discoid lupus. Then about six months into this, she really sent downhill and developed neurological symptoms over the course of several weeks (which at first I didn’t recognize as such–I thought it was just arthritis), which drastically got worse in the last 4 or 5 days of her life and ended up that she couldn’t walk, couldn’t blink, had a seizure, and in the end, had to be humanely euthanized. After extensive tests (bloodwork/x-rays) revealed only a slightly enlarged liver), and after she ended up having the seizure, inability to blink, etc., my vet concluded that it was a brain tumor which didn’t show up on the x-rays. Now: he feels that all of this had NOTHING to do with the Comfortis, and I should add that he is a fantastic vet who I’ve been going to for 14 years, and usually I trust his opinion. But in this case, even though my dog was old, she was FINE before the Comfortis and it is just quite a coincidence if it had nothing to do with all these strange things happening. I will never use Comfortis again and strongly recommend that other folks think twice about it.

    Comment by Edna — January 18, 2010 @ 1:33 pm

  11. Last month I noticed My 3 1/2 year old doberman
    sitting on my bed looking rather strange. Then he started to twitch, seizure like, mostly his face and ears. The rest of the evening he was not himself, decreased energy. I had given him
    comfortis and hearguard plus that day. He had been on this for approx 6 months. Looking back I think I have seen similar reaction but not so pronounced and it did not last long that I did not think anything of it. This week I took a new rescue dog to a new vet because I have relocated. This vet does not prescribe comfortis. So I decided to research the drug..
    I will only be using topical flea protection from now on.

    Comment by Fran — February 13, 2010 @ 4:42 pm

  12. My healthy (confirmed by vet visit and blood work in Feb) 10 year old bichon frise had an adverse reaction to comfortis and heartgard (stroke like symptoms) at the beginning of April. This past week she was diagnosed with diabetes. Wondering if there is a connection????

    Comment by Kim — July 3, 2010 @ 7:31 pm

  13. My dog was on off label use of ivermectin to treat mange and my vet was neglegent and put her on comfortis to prevent fleas, of course at the time I did not know about the FDA warning. My dog died within hours of taking the comfortis. As owners we must remain educated about all medications

    Comment by cassidy — September 22, 2010 @ 8:33 am

  14. Dear James,
    I came across your site while to trying to research the dangers of Comfortis. I have a oner year old Boxer, a six year old Rat Terrier and a 6 year old Miniature Rat Terrier, all three of my dogs were healthy. Unfortunately I went to Petsmart’s Banfield Clinic and was able to purchase 3 tablets (depending on weight) to give to all three of my dogs for flea control. I was able to attain this product without ever seeing or speaking to a veterinary Dr. This was the first time that I had used this product and gave all three of my dogs a Comfortis tablet Sunday night (4-17-11) and all three of my dogs and within hours all three of my dogs began to vomiting severely. Fortunately the vomiting lasted only a few days but my miniature Rat Terrier began to become very disoriented, began to tremble,his eyes became hazing and glazed and his pupils were dilated and had become blind 4-20-11. Just early that day he had been chasing my Boxer around the yard and doing well. I called the 1800 number for Comfortis/Alanco and spoke to one of their Veterinarians by the name of Dr. Rosencran and at her request I to take him to my vet to be looked at their expense. My Vet completed a full check up and eye stain on my dog and could not see anything that would have caused my dog to go blind within hours. My Vet recommended my dog be referred to see a special veterinary ophthalmologists. Alanco immediately called my vet and approved the ophthalmologist visit for my dog next week. The more I research the side affects of Comfortis the more I am reading about dogs going blind in the same manner that my dog did. It sounds to me that Alanco is well aware of what’s going on and knows more than they are saying! Feel free to contact me at yrwilson1@aol if you have any questions or comments.

    Comment by Yvette — April 24, 2011 @ 8:42 am

  15. Our dog princess died this morning at the age of 10. Just last night she was as playful and funny as always. In less than 10 hours after being given Comfortis we woke up to find her dead. There are many similar stories online where peoples dogs died within hours of being given this flea medication. We found out too late.
    If you know of anyone treating their dogs with this poison ask them to stop immediately. It’s not worth the risk.
    She was our girl. We loved her so much. Now we’re left with a void that can never be filled, and a profound sadness that no words can describe.

    Comment by Keith — May 26, 2011 @ 10:22 am

  16. My 14 y/o dog has been on ivermectin for mange which he had last year and it helped a lot. He took his monthly Comfortis yesterday morning and I came home to find him in a drunken stupor, still able to walk but falling. The vet told me these should NOT be taken together but felt that he would be okay. The tail is wagging and he is rallying, but I wanted to get the word out that these meds are bad together.

    Comment by Paula — June 21, 2011 @ 9:20 am

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