I almost killed my Australian Shepard today!

megs2May 1, 2011

This is not the first time he has had frontline plus applied, but buddy it was the last! It had been about 45 minutes, he started panting heavily,pacing,and his eyes were very bloodshot.I could feel his heart pounding against my hand. He was in severe acute distress.

I am a nurse, maybe that's why I knew he was about to have a heart attack. His eyes were so red from his bloodpressure going very high. I immediately gave him 2 benadryl(25mg each), picked him up and put him in the tub. I used joy dish liquid since it cuts grease, and I knew Frontline is oil based. I got every bit of that #%$#$* off my boy.

Thank God is all I can say. Thank God I had that benadryl in the house! I know he would have had some residual problems from that, like heart or liver problems, if he did not die. He is only 1 1/2 years old; and a great big healthy beautiful boy. And yes, I used the appropriate dosage.

What I don't know is; what the #$** happened??!!!He has had this Frontline before, and he was fine. I eat organic, clean my house with organic products, and put poison on my dog. I feel like an idiot! Now I'm about to cry, because I almost killed my good boy.

Please everyone...keep benadryl in you house if you have pets! Yes 50mg was alot for me to give him, but I knew it would not kill him. He did sleep well.

Any suggestions on what I should do now? My Vet says," Oh no, frontline could not have done that". Uhhh... yes it can, and it did!! Any advice is appreciated. My Vet was about as helpful as my cat.

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Im very sorry you went through this. I think each time this happens the owner needs to inform the company and a warning label needs to be put on the product.
I have copied some information for you and any other herding dog owners.....
Glad you and your dog are okay.

Do you own a collie or an Australian shepherd? Have you been cautioned that they may be particularly sensitive to certain drugs, or have you heard not to give them certain medications? Parasiticidal drugs, especially the avermectin group of dewormers: ivermectin (Heartguard�), selamectin (Revolution�), milbemycin (Interceptor�), and moxidectin (ProHeart�) may result in toxicity of the central nervous system when given above therapeutic levels. Do you ever wonder why these potentially lethal reactions occur when most other breeds have a wide safety margin when using these drugs? Most idiosyncratic drug reactions in veterinary patients are seen in herding breeds of dogs or in cats, which have a narrower therapeutic dose range for these drugs. These same breeds of dogs can be sensitive to various treatments such as chemotherapy as well.
It has recently been determined that some herding breeds of dogs have a single mutation in a gene coding for a particular protein (P-glycoprotein) that will drastically affect the absorption, distribution, metabolism, and excretion of a variety of medications used in veterinary medicine. In herding breeds of dogs there is a defined mutation called MDR1-1∆ (multidrug resistance gene), also called ABCB1, which affects P-glycoprotein function.
P-glycoprotein is a rather larger protein that functions as a pump to transport drugs across cell membranes. This pump requires energy in the form of ATP allowing it to function against steep concentration gradients. When a drug is transported by P-glycoprotein it is actively transported from intracellular (within the cell) to extracellular space (outside the cell). It is speculated that this protein serves an important function in protecting living beings, from one-celled organisms to the most complex animal systems, by minimizing that particular being�s exposure to potentially toxic substances. The protein functions by pumping toxins out of protected sites and promoting their excretion and elimination.
The primary absorptive site for orally administered drugs is the villus tip of enterocytes (intestinal cells) located with the gastrointestinal (GI) tract. P-glycoprotein is present on the luminal border of these intestinal epithelial cells where it transports drugs from the cytoplasm back into the intestinal lumen where they can be eliminated. In this way, P-glycoportein plays an additional role in drug elimination by limiting intestinal absorption and promoting fecal excretion of potentially toxic substances.
There are many barriers throughout the body protecting what is termed "privileged tissue". These barriers include the blood-brain, blood-placenta barrier, and the blood-testes barrier. The term "privileged" means that very few substances are allowed across this barrier. P-glycoprotein has an important function in this barrier by minimizing the distribution of a substance to these tissues. In dogs totally lacking this protein they are considered to be homozygous for the defect (in their genetic make-up they have 2 genes for the MDRI-l∆ mutation) and ivermectin a common dewormer and heartworm preventative, in even low doses will induce neurologic toxicosis. This is true for many other drugs as well, even including many chemotherapy agents like doxorubicin and vincristine, and cardiac drugs such as digoxin and corticosteroids.
P-glycoprotein itself does not have any metabolic functions but it does work in conjunction with the CYP3A enzyme. The CYP3A enzyme is one of the most abundant cytochrome enzymes and is responsible for the metabolism of approximately 60% of all known drugs.
Complicated relationships may occur between P-glycoprotein, CYP3A, substrates, and even other substances called inhibitors. A drug inhibitor is a drug that interferes with the P-glycoprotein/CYP3A substrate system. Drugs such as Erythromycin, Ketoconazole, Cyclosporine and Tracrolimus are all drug inhibitors. Using any one of these inhibitor drugs concurrently with another drug eliminated by P-glycoprotein substrates such as Vincristine or Digoxin may result in drug toxicosis regardless of whether the MDR1-1∆ mutation is present or not..
Breeds in which the MDR1-1∆ mutation has documented occurrences include: Longhaired whippet, Silken windhound, Collie, Australian shepherd, English shepherd, the McNab collie, Old English sheepdog, Shetland sheepdog, and the German shepherd. White-coated dogs such as the white German shepherd have a greater frequency of the MDR1-1∆ mutation than do other colors.
A study published in the American Journal of Veterinary Research during 2002 found that 75% of the collies from the Northwestern United States had at least one mutant gene (heterozygous) for the MDR1-1∆ mutation, while 35% of those had two mutant genes and are termed homozygous for the defective gene. In Australian sheepdogs, 16.6 % of the population carries the defective gene, while Shetland sheepdogs are affected at an 8.4% level and Old English sheepdogs at a lesser 3.6% level. Other herding dogs such as the bearded collie and Australian cattle dog have not been shown to harbor the defective gene, presumably as a result of their varied ancestry.
It is important to test for the MDR1-1∆ mutation for it allows veterinarians to determine whether it is safe to administer drugs that are eliminated by the P-glycoprotein. A simple cheek swab sample may be submitted for DNA analysis to determine the existence of the MDR1-1∆ mutation in any particular pet. These samples should be forwarded to:
Veterinary Clinical Pharmacology Laboratory (VCPL)
College of Veterinary Medicine
Washington State University
In pets reacting to acute exposure to avermectins or other drugs and treatments eliminated by P-glycoprotein, the clinical signs will become severe within a few hours of exposure. Most of the clinical signs relate to depression of the Central Nervous System (CNS) and include ataxia, weakness, and recumbency (the pet is unable to get up), and in severe cases a coma may develop. The pet may also appear to be blind and muscle tremors may sometimes occur. Additional clinical signs include mydriasis (dilated pupils), hypothermia (low body temperature), shallow breathing, vomiting or salivation. Clinical signs may persist for days or weeks, dependent upon the type of drug resulting in the toxicity.
Temporary relief is sometimes achieved with physostigmine, neostigmine or treatment with picrotoxin. Additional treatment is supportive and may require: fluid therapy, respiratory support, maintenance of body temperature, and/or the use of a feeding tube. Length of treatment depends upon the half-life of the drug causing the toxicity. The half-life of a drug refers to the length of time it takes to eliminate 1⁄2 of the drug in one individual�s system. With ivermectin the toxicity typically lasts 2 days, while it may take up to 11 days to eliminate selamectin or up to 19 days for moxidectin.
Diagnosis is typically made through exposure to the medication, knowledge of the breed of dog, and classical clinical signs.

Bonagura, John, and David Twedt, Ed. Kirk�s Current Veterinary Therapy XIV. Saunders/Elsevier. 2009. Pp. 125-127.
Mealey, Katrina, DVM, PHD. "Adverse Drug Reactions in Herding-Breed Dogs: The Role of P-Glycoprotein". Compendium on Continuing Education for the Practicing Veterinarian. Pp. 23-33.

    Bookmark   May 2, 2011 at 12:37AM
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Here's the link to Washington State University's lab and instructions for ordering and submitting the mutant MDR1 gene test. It's certainly worth the cost of the test, esp. since your Aussie has already had one negative drug reaction.


Here is a link that might be useful: mutant MDR1 gene test

    Bookmark   May 2, 2011 at 12:46AM
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spedigrees z4VT

Fipronil is not on the list of medications that MDR1 dogs are sensitive to. The list is here:


Dogs do not have heart attacks as humans do. However this sounds like an extreme reaction to something. Fipronil has a good safety record, but perhaps your dog could have developed an allergy to the drug. It seems unlikely but possible. A spider bite or bee sting could also cause an anaphylactic reaction.

It is frightening when a pet has a severe reaction, and it is good to have benedryl or epinephrine on hand.

    Bookmark   May 2, 2011 at 9:59AM
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spedigrees z4VT

Not sure how I mistakenly posted a link to television scheduling, but here is the link I meant to post listing drugs that cause reactions in dogs with the MDR1 gene:


    Bookmark   May 2, 2011 at 12:15PM
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Wow ... I am so sorry you went through this. Guess you should give your vet this information to read. (And find a new vet?)

And I am glad I read through this ... my Lily is part German Shepherd, part Australian Shepherd ... and my Rocky is part collie. I haven't had to use any flea control in years, but I need to remember this for the future.

    Bookmark   May 2, 2011 at 12:52PM
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If you dont have a flea problem you might want to just put out a bit more effort to keep them from moving in and settling in, once you have a flea you have thousands. Cleaning any fabrics your dog has regular contact with and giving fido a bath when out in the fields (where fleas and eggs can come in contact with your dog) regular grooming can help find flea dirt as well.
While garlic and yeast may have alot of popular press research states they do little to curb fleas.

    Bookmark   May 2, 2011 at 1:41PM
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Spedigrees thank you so much for that information!!!
I have never heard of this before. I need to alert his breeder so she can contact the other owners.

Please excuse my ignorance,but what is fipronil? Is it an ingredient in another topical like advantage?... I'll google it.

He is currently taking interceptor, but it looks like as long as the dose is not too high for him, he should be alright. Am I in my tired state of mind, understanding this correctly?

I appreciate all who are offering information to me. I only have my computer at night, or I would have thanked you earlier. Jackson thanks you all too. Woof.

    Bookmark   May 3, 2011 at 12:29AM
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spedigrees z4VT

Fipronil is the active ingredient in Frontline.

Fipronil is NOT one of the drugs that causes sensitivity in collie type dogs with the MDR1 gene.

Your dog may have had a reaction to fipronil but it is not because he has or doesn't have the MDR1 gene. There is NO drug on the market that has not caused reactions in a small percentage of individual users: canine, human and other species, and fipronil (Frontline) has a good safety record. It is no more likely for a dog with the MDR1 gene to have such a rare reaction to fipronil than a dog without the gene.

    Bookmark   May 3, 2011 at 4:26PM
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spedigrees z4VT

Yes, interceptor (milbemycin) and all the other monthly heartworm preventatives are safe (because of their low dosage) for dogs with or without the MDR1 gene. It is at higher doses that ivermectin, milbemycin and related compounds cause problems for dogs with the MDR1 gene.

You can't really know for sure that it was the fipronil (frontline) that caused his reaction. However the coincidence suggests a link. If Jackson were my dog I would switch him to a different monthly flea control that does not contain fipronil, advantage for instance.

I hope he stays well. That must have been terrifying.

    Bookmark   May 3, 2011 at 4:39PM
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Have you found a substitute flea preventative that works for your Aussie? My dog is part Aussie and tested positive for the MDR1 defect so she can't have certain meds. She was on Frontline (not Plus) for 5 months no problem, the 6th month application her hindleg was paralysed. It resolved itself but scared me to death, she was only 8 months at the time. Now I find (at 2 years) she is allergic to fleas, yeast and maybe grass. I've had her on Program tablets but that isn't working and the vet suggests I get a more broad-covering product, recommended I check out Comfortis. I was also steered toward Advantage (not Multi). Have you had any luck with a product? Thanks!

    Bookmark   October 4, 2011 at 6:29PM
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The vet sounded like my doctors. The med I prescribed can't cause that!!!! I got a new doctor.

I am glad you were at home to save him. I would research side effects if you find proof that Frontline causes reactions like that, confront the vet. Get a new one if you have to.

    Bookmark   October 4, 2011 at 7:00PM
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Fipronil is one of the safest topical flea treatments. I have a breed that has a unique physiology and is sensitive to drugs. I use only Frontline Plus. Fortunately with no adverse reactions ever. Please continue to research before trying anything else for your pup. A month or so ago a friend's dog (same breed as mine - greyhound) had a severe skin reaction that looked like a burn from Frontline. Your vet's disbelief is understandable but not acceptable. She needs to file an adverse incident report.

General FDA on topicals



Here is a link that might be useful: Vet reporting portal for adverse events

    Bookmark   October 4, 2011 at 7:49PM
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I would certainly report this to the county vet as well as the Frontline people. It will reach the most people that way, though I still have a hard time believing it... coincidence is still a possibility.

    Bookmark   October 5, 2011 at 1:32AM
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Where did you get the Frontline from? Some places pass off junk as Frontline when it's not Frontline at all.

And it's not poison for your dog. Flea and tick preventative are important and better than your dog getting parasites and Lyme disease. You just need to find one that your dog doesn't react badly to.

Not every medication is safe for every person. Same goes for animals.

    Bookmark   October 5, 2011 at 2:14AM
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I saw my vet at a doggie event recently and told him Frontline plus wasn't working that well for my dogs and cats, and I was thinking of Advantage next time. He flatly said Frontline is the best and he doesn't like Advantage.

    Bookmark   October 5, 2011 at 1:36PM
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I hear good things about Advantix.

    Bookmark   October 6, 2011 at 2:14AM
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Advantix contains permethrin which can be dangerous in some breeds. A brand I personally would not use. Doesn't mean others don't have any issues with, I just prefer safer flea preventives.

    Bookmark   October 6, 2011 at 7:53PM
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If you prefer all natural stuff, Sentry makes something called Natural Defense that's relatively effective.

Although permethris is plant based, I believe and therefor natural. Or maybe I'm thinking of something else.

    Bookmark   October 7, 2011 at 10:01PM
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I think you're thinking of pyrethrin minnamouse (from chrysanthemums). Advantix is permethrin, a chemical, not from plants.

    Bookmark   October 8, 2011 at 6:55AM
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Must be. Anybody tried the Natural Defense?

    Bookmark   October 8, 2011 at 10:07PM
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Hi, you can use Avon's Skin So Soft, to kill flea's. It really works. It has a wonderful smell also. It will kill fleas and you can use it on cat's,dog's, I even used it on my horse for flies. It is great stuff. I hope you have great use with it. I used Frontline Plus on my Alaskan Malamute last night and she is not doing well. She is acting very ill. She is not her self, she is acting sick and sleepy and I am calling the vet now. I called the poison control center and they told me that Frontline Plus is completely safe and there is nothing to worry about. I told her about the medication she was on and I said there could be a drug interaction and the lady stated no not at all, but I think so. After reading what you have written I am very worried and I am sending this to my vet. I just hope my dog will be alright, she has never acted like this before on Frontline Plus but she has never been on this medication before. I wish you all the best. Cat

    Bookmark   June 9, 2013 at 6:40PM
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My 4# Chihuahua had a reaction to Frontline so I went to Advantage. Now that she is gone my 7# took the Frontline and didn't have a reaction. I made sure I was home all day just in case.

    Bookmark   June 13, 2013 at 4:51AM
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Hmm it seems ive heard about a reaction like this from somewhere else ..i have also heard of frontline straight up not working ... I havent had either of these problems ... Ive used frontline plus , advantage , advantage multi, and am currently using k9 advantix ll .. We live in a wooded area and i must have something for tick prevention as well...

    Bookmark   June 20, 2013 at 12:40AM
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My aussie had the same reaction as megs2 after we administered frontline...within 2-3 hours. Thankfully she is back to normal, now our biggest issue is tick control. We have been using a apple cider mix, but that is not really preventing the ticks. We tried a tick collar, but after wearing for several hours - she appeared to have another adverse reaction. She has been tested for the mutant gene, results show she does not carry it...
I don't want to keep experimenting with her...any suggestions? We are pulling ticks off of her daily!

    Bookmark   April 30, 2014 at 8:45PM
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