51 replies to this topic

[Pipedream Farm]

This question comes up periodically and the uncertainty among owners and veterinarians stems from extrapolating drug reactions in other herding breeds to Border Collies and from overdosing dogs with livestock sources of Ivermectin used off label as heartworm preventive. All of the heartworm preventives currently on the market are in the same class of drugs, avermectins; and therefore can have the same side effects. The drug companies have been aware that some Collies are sensitive to avermectins and have determined the minimum effective dosage to obtain heartworm prevention and the dosage at which these sensitive Collies show reaction (in terms of multiples of the minimum effective dose). This information can be found on the product labels for all heartworm preventatives. Within the last few years veterinary research has determined the biological source of this sensitivity in Collies and has isolated and the gene responsible for this sensitivity (Breed distribution and history of canine mdr1-1Δ, a pharmacogenetic mutation that marks the emergence of breeds from the collie lineage). As of the fall of 2005 over 300 pure bred Border Collies have been tested for this mutation and zero have been found to have the multidrug sensitivity gene (mdr1-1Δ). Even if your Border Collie does have this mutation, the heartworm preventive dose has been shown to be sufficiently low to not elicit a reaction in known sensitive Collies.

UPDATE as of 11/15/06: From Katy Robertson at UC Davis, where the test is performed:

"We have tested 362 Border Collies (not controlled for relatedness) to date and have seen the MDR1 mutation in only 1 dog. This dog was a rescue with unknown pedigree; therefore, we didn't include the dog in our findings."

Based on the above information, this drug sensitivity gene has not yet been found in purebred border collies in this country. Since the mutated MDR1 gene is fairly common in many breeds that can look like border collies, dogs with unknown pedigrees should not be counted as border collies. However, some testing institutions log in breed data based solely on the owner's description of the breed. The ABCA Health and Genetics Committee will continue to follow the verified statistics of this mutation in purebred border collies.


12/12/07 Katy Robertson at UCDavis reports no pure bred Border Collies found with the mutation; the number of tests being run has decreased and few additional Border Collies have been tested. (edited by Mark Billadeau)

**********

I have pulled from the Boards posts to help clarify the issues with heartworm preventative sensitivity and links to websites with additional information.

Important points to remember

1) The normal dose of ivermectin used for prevention of heartworm in products such as Heartguard (6 micrograms/kg) is not documented to cause the toxicity associated with this mrd1 mutation in collies or any other dog. It is only when higher doses are used, often by people mistakenly thinking the cattle/sheep dose is appropriate for dogs, that toxic symptoms appear in susceptible dogs.

2) Any of the avermectins, the class of chemicals ivermectin belongs to, are capable of producing the same toxicity in affected dogs when used at high doses. The commonly held belief that heartworm preventives such as Interceptor are safer than Heartguard is incorrect. Both products are safe at the low dose used. However, there are confirmed reports that moxidectin, which is used in the six month injectable for heartworm prevention, has caused neurotoxicosis in susceptible collies.

3) Any breed of dog can suffer from toxicity and death from ivermectin and the related class of drugs if they consume high enough levels to penetrate the blood-brain barrier. Levels of ivermectin shown to cause toxicity in beagles, a breed that does not have the mdr1 mutation are 2.5 - 40 mg/kg which is greater than 200 times the therapeutic dose.

Special considerations for farm dogs

An important consideration not everyone is aware of is that farm dogs often consume ivermectin or other avermectins in the manure from recently treated stock. Merck reports an apparent half-life for ivermectin of 1-1.5 weeks in sheep manure from sheep wormed with the standard drench dose of 200 micrograms/kg. They also estimate typical soil incorporation rates for manure from treated sheep to range from 0.16 ppb to 5.1 ppb. (From http://www.fda.gov/c...31-392FONSI.pdf ) Therefore, it?s possible for collies and other breeds known to have the mdr1 mutation to consume a toxic dose of ivermectin from eating the manure of recently wormed stock. The timing of worming stock with avermectins should also be taken into account when giving farm dogs heartworm preventative to prevent accidental overdose.

Partial list of drugs known or suspected to cause problems in dogs with the mdr-1 mutation

Ivermectin (antiparasitic agent)
Loperamide (Imodium?; over-the-counter antidiarrheal agent)
Doxorubicin (anticancer agent)
Vincristine (anticancer agent)
Vinblastine (anticancer agent)
Cyclosporin A (immunosuppressive agent)
Digoxin (heart drug)
Acepromazine (tranquilizer)
Butorphanol (pain control)

Partial list of drugs thought to have the potential to cause problems with the mdr-1 mutation

Ondansetron
Domperidone
Paclitaxel
Mitoxantrone
Etoposide
Rifampicin
Quinidine
Morphine

Reference: Neff, et al, 2004

As far as the internet reports on cases of ivermectin sensitivity in border collies, as I said, I contacted the people who do the gene test and they said no border collies had been confirmed to have the mutation. I asked specifically about the unconfirmed reports and they are still unconfirmed. The number of border collies that've had the test is now over 300.

C Denise Wall, PhD

Here's a little more detail on Denise's point #2.

So-called "ivermectin" sensitivity is actually sensitivity to a broad class of compounds due to a basic defect in the blood-brain barrier. Normal dogs are protected from acute and often fatal neurotoxicoses when these compounds are administered as pharmaceuticals (including ivermectin) by P-glycoprotein, an ATP-dependent drug transporter that moves a broad spectrum of substrates across several tissue borders throughout the body. The normal gene encoding for P-glycoprotein is MDR1.

Anti-helminthic pharameuticals that are P-glycoprotein substrates include the family of compounds known as macrocyclic lactones. These compounds exert their anti-helminthic properties by causing neurotoxicosis in a number of invertebrates (including helminths and arthropods) by potentiating ligand-gated chloride ion channels in the peripheral nervous system. Generations of macrocyclic lactones known as avermectins have been developed for veterinary use, decreasing their toxic side effects to normal animals (without the mdr1-1Δ mutation).

These compounds include: ivermectin (HeartGard), milbemycin oxime (Interceptor and Sentinel), moxidectin (Proheart), selamectin (Revolution), and doramectin (Decomax).

Given the mechanism for toxcity, there is no reason to consider milbemycin oxime safer for dogs with the mdr1-1Δ mutation than ivermectin. The monthly oral dose of both ivermectin and milbemycin oxime has been administered for heartworm prophylaxis to Collies homozygous for mdr1-1Δ without incident and both have been shown to have similar pharmaceutical margins of safety in sensitive Collies (Tranquilli et al. 1991). (source American Working Collie Association)

Washington State University Multidrug Sensitivity Study

Testing your dog for the mutation


The Bottom Line:
Based upon current information, all of the monthly heartworm preventatives are equally effective and equally safe.

Mark Billadeau

[ 11-16-2006, 10:01 AM: Message edited by: Eileen Stein ]

[juliepoudrier]

I vote for this topic to get a sticky in the H&G section and maybe a copy in the FAQs.

J.

[Denise Wall]

As far as reported ivermectin sensitivity in border collies, here is a relevant excerpt from Katy Robertson (UC Davis) where the test is done:

"In addition, I've tested 3 BCs that had severe neurological toxicity after ingesting horse ivermectin paste. The dogs each ate some of the paste during a routine deworming of horses. None of these dogs had the MDR1 mutation. This seems to support the theory that there is a dose response curve with these drugs. Given a large enough dose, even a dog with a normal blood-brain barrier is unable to prevent the drug from reaching toxic levels in the brain and CNS."

There’s also a chance there is a different as yet undiscovered mutation from the MDR1-1 mutation causing ivermectin sensitivity in border collies.


The reason we're using UC Davis data to follow the whether or not this MDR1-1 mutation is discovered in border collies is because they are meticulous about determining the actual breed purity of individuals with the mutation before reporting statistics for a certain breed. Other breeds such as Australian Shepherds known to have this mutation can look like border collies, and are not uncommonly crossed with border collies. Therefore, it is important to be able to determine the parentage for a dog called "border collie" by its owners. Other labs that perform this test categorize dogs based solely on the owners’ description of breed. There is a German paper that reports border collies with the MDR1 mutation at an very, very low frequency (J Vet Pharmacol Ther. 2005 Dec;28(6):545-51. Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany. Geyer J, Doring B, Godoy JR, Leidolf R, Moritz A, Petzinger E.) However, I have the manuscript and can find no assurance in the description that the breed purity was firmly established in any of the breeds.

So based on what we know here in the US from reliable sources, there is no evidence this particular mutation is a problem in pure bred border collies. We will continue to follow this as more dogs are tested to determine if there is indeed a low frequency of this mutation present in border collies and to determine the risk. However, clearly, given the data, the frequency of this mutation in border collies is extremely rare at best.

Given that “collie breeds” in general are known to have this mutation, misinformation is given out all the time (even by those who should know better) that includes border collies as a susceptible breed. A vet at Novartis recently told a border collie owner whose dog was having seizures that three out of four border collies have the MDR1-1 mutation. This owner was convinced her dog’s seizures were caused by a drug her dog was sensitive to because of MDR1 sensitivity. Her dog was tested and negative for the MDR1-1 mutation. I hope this misinformation didn’t delay the determination of and treatment for the actual cause of the seizures.

In conclusion, I will again stress, there are thousands and thousands of different mutations, probably at least a few in each individual, that can cause disease in the progeny when paired with another mutation like it in a mate. There is probably some border collie somewhere carrying a disease mutation for every, or nearly every disease ever discovered. The recent hysteria over possibly finding one working border collie carrier for this or that newly discovered mutation is completely unrealistic in the grand scheme of things. As I said, there is undoubtedly at least one working border collie somewhere out there with nearly every mutation. The mutations discovered so far such as CL, TNS, etc., are the tip of the iceberg. The only reason they’ve gotten attention is because an otherwise rare mutation that would never (or almost never) have met up with another like it to cause disease is much more likely to do so when related individuals are bred together. This type of breeding is common is show dog circles so this is where these diseases from rare mutations are occurring at a noticeable level. A sensible breeding strategy is the best defense against the occurrence of disease from these rare mutations common in all animals. If the frequency of the mutant gene has become significant in a population, that’s another story. That’s why it’s important to distinguish between an unrealistic strategy of “if there’s any border collie anywhere that has this mutation then every border collie should be tested for it” and “there is sufficient evidence to support testing for the mutant gene in this breed, population, or line of dogs.” At some point common sense must prevail.

Denise Wall, PhD (Biochemistry)
ABCA Health and Genetics Committee Member

[Mark Billadeau]

I have written one of the authors of Geyer, J. Doring, B. Godoy, J R. Leidolf, R. Moritz, A. Petzinger, E. Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany. J Vet Pharmacol Ther. 28(6):545-51, 2005 Dec. requesting more details on the border collies found with the mutation. Just as Denise Wall suspected, the breed designation is by owner description (and Vet confirmation). In other words, if the dog was not a registered border collie, but looked like one, it was included as a border collie. This makes it difficult to ascertain the relevance of the mutation in these 3 dogs to the gene pool of pure bred border collies.

Mark

Dear colleague,
In general we accept the owners declaration and a confirmation by the vet who took the blood sample.
With best regards
Ernst Petzinger
Institut für Pharmakologie und Toxikologie
am Fachbereich Veterinärmedizin
Frankfurter Str. 107
35392 Gießen
Tel: (06 41) 99-38401
Fax: (06 41) 99-38409
E-Mail: Ernst.Petzinger@vetmed.uni-giessen.de

[Rave]

Hi all, just wondering if anyone had any updated information on whether there have yet to be any reported purebred BCs with the MDR1 gene mutation?

[MaryP]

Hi all, just wondering if anyone had any updated information on whether there have yet to be any reported purebred BCs with the MDR1 gene mutation?

According to Washington State University website, there have been fewer than 5. I don't know if any were known purebreds. I have a test kit that I'm going to use for my foster dog, who is a rescue, but I'd eat my shorts if he weren't a purebred. I haven't sent the sample in, yet, but will be doing so. I don't normally test foster dogs, but this dog has had so many problems that I don't want to take any chances.

[Rave]

Actually the WSU site lists <5%, which doesn't really tell us much (it could just be their lowest reporting threshold is 5%). And based on the info here, no way of knowing if the ones listed as Border Collie are actually purebred.

[MaryP]

Actually the WSU site lists <5%, which doesn't really tell us much (it could just be their lowest reporting threshold is 5%). And based on the info here, no way of knowing if the ones listed as Border Collie are actually purebred.

That is what I meant to say.

[Mark Billadeau]

The last email from Mealey etal indicated 3 (out of 124) Border Collies; however, those who have personal knowledge of the raw data indicated that these dogs may not have been purebred Border Collies. I have made another email request for an update on the data in the WSU/UCDavis testing.

In the meantime here are a few reports in the literature on the subject. All of these reports indicate the mutation is either not present or present a very low level. None of the reports indicate that anything more than owner or veterinarian "say so" was required to categorize the breed of dog.


Mark

Presence of the ABCB1 (MDR1) deletion mutation causing ivermectinhypersensitivity in certain dog breeds in Belgium

The 9 Bearded Collies and 35 Border Collies evaluated in the current study did not possess the deletion mutation (Table 1), which, for the Bearded Collies, is in accordance with previous findings (Geyer et al., 2005b). Two independent reports from Germany and the USA (both conducted on more than 300 dogs) showed that less than 2% of the Border Collies possessed the mutation in the ABCB1 gene (Geyer et al., 2005b; Mealey and Meurs, 2008).

Frequency of the nt230 (del4) MDR1 mutation in Collies and related dog breeds in Germany

The frequency of the mutated MDR1 allele varied markedly between these breeds and was highest for Collies (54.6%), followed by Shetland Sheepdog (30.0%), Australian Shepherd (19.5%), Wa¨ller (18.5%), Old English Sheepdog (6.3%), and Border Collie (0.6%) (Table 1).

In 334 Border Collies only one dog with homozygous and two dogs with heterozygous mutated MDR1 alleles were identified, indicating a very rare occurrence of the nt230 (del4) MDR1 mutation in this breed.

Frequency of the mutant MDR1 allele associated with multidrug sensitivity in a sample of herding breed dogs living in Australia.

Abstract
A study was performed to determine the frequency of the mutant MDR1 allele associated with ivermectin sensitivity in a sample of Collies and other herding breeds living in Australia. Buccal swab samples were collected from 33 Collies, 17 Australian Shepherds, 7 Border Collies and 7 Shelties for determination of MDR1 genotype. DNA was extracted and the polymerase chain reaction was performed to amplify a 148 base pair (wildtype MDR1 genotype or 144 base pair (mutant MDR1 genotype) amplicon containing the MDR1 mutation. Sequence analysis was performed to determine the genotype of each dog. Adequate quantities of DNA for unequivocal genotyping were obtained from 61 of 64 samples. The previously described MDR1 mutation was identified in Collies, Australian Shepherds and Shelties living in Australia, but not in Border Collies (although sample numbers were low). Twelve percent (4/33) of the Collies studied were homozygous for the normal allele (normal), 64% (21/33) were heterozygous (carrier) and 24% (8/33) were homozygous for the mutant allele (affected). Results of this study indicate that a high percentage of herding breeds presenting to veterinarians in Australia harbor the MDR1 mutation, thus impacting some therapeutic decisions.

Breed distribution of the nt230(del4) MDR1 mutation in dogs.

published in 2010
Abstract
A 4-bp deletion mutation associated with multiple drug sensitivity exists in the canine multidrug resistance (MDR1) gene. This mutation has been detected in more than 10 purebred dog breeds as well as in mixed breed dogs. To evaluate the breed distribution of this mutation in Germany, 7378 dogs were screened, including 6999 purebred and 379 mixed breed dogs. The study included dog breeds that show close genetic relationship or share breeding history with one of the predisposed breeds but in which the occurrence of the MDR1 mutation has not been reported. The breeds comprised Bearded Collies, Anatolian Shepherd Dog, Greyhound, Belgian Tervuren, Kelpie, Borzoi, Australian Cattle Dog and the Irish Wolfhound. The MDR1 mutation was not detected is any of these breeds, although it was found as expected in the Collie, Longhaired Whippet, Shetland Sheepdog, Miniature Australian Shepherd, Australian Shepherd, Wäller, White Swiss Shepherd, Old English Sheepdog and Border Collie with varying allelic frequencies for the mutant MDR1 allele of 59%, 45%, 30%, 24%, 22%, 17%, 14%, 4% and 1%, respectively. Allelic frequencies of 8% and 2% were determined in herding breed mixes and unclassified mixed breeds, respectively. Because of its widespread breed distribution and occurrence in many mixed breed dogs, it is difficult for veterinarians and dog owners to recognise whether MDR1-related drug sensitivity is relevant for an individual animal. This study provides a comprehensive overview of all affected dog breeds and many dog breeds that are probably unaffected on the basis of approximately 15,000 worldwide MDR1 genotyping data.

[Rave]

Thanks Mark.

[Mark Billadeau]

Dr Mealey responded to my email request for an update. She did not provide exact numbers (tested, clear, carrier, affected) but did indicate that the rate of the mutation is about 1% in dogs identified as Border Collies.

She also noted that there is a sub population of dogs identified as Border Collies that do not have the MDR1 mutation but experience severe toxicity when treated with the chemotherapeutic agent vincristine. They are trying to identify the cause of this sensitivity.

Mark

[katanddd9]

hi all.i used revalution on my aussie and never had a problem.are you saying no to the heart warm and that drug for my bc pup.thanks dana

[katanddd9]

hi i have read all the science on revalution and have no fears of the drug.thanks dana

[Barefoot]

Why take the chance when there are alternatives?

[juliepoudrier]

Barefoot,
Are you aware of an alternative that is not in the same chemical class as ivermectin, milbemycin oxime, etc.?

From the American Working Collie website drug sensitivity web page:

Anti-helminthic pharameuticals that are P-glycoprotein substrates include the family of compounds known as macrocyclic lactones. These compounds exert their anti-helminthic properties by causing neurotoxicosis in a number of invertebrates (including helminths and arthropods) by potentiating ligand-gated chloride ion channels in the peripheral nervous system. Generations of macrocyclic lactones known as avermectins have been developed for veterinary use, decreasing their toxic side effects to normal animals (without the mdr1-1Δ mutation). These compounds include: ivermectin, milbemycin oxime, moxidectin, selamectin, and doramectin.

J.

[Ross Bash]

Thanks to all of you, and especially to Mark Billadeau, for provding such helpful and detailed information.

[Gary_and_Karen]

On the recomendation of our vet we have had our dog on Triflexis for about 3 or 4 months now and I don't think she has yet any any negative reactions though I now remember seeing a very occasional, very slight tremor in her leg but I thought that was just some of her nervous energy being a very active dog.  (our dog is a Border Collie / Beagle mix)

 

Anyhow, I was searching online to see if there was a cheaper source for Triflexis and found this web page and now I am very leary about giving my dog any more Triflexis at all, even though so far she has been ok, but some people have not seen any bad reactions till many months after their dog being on it.   

 

https://www.facebook...ifexisKillsDogs

 

below are just some of the quotes from the above link.......

 

It has killed THOUSANDS of dogs all around the world, and that's only the ones we know about. Most people do not bother to report such incidents.

  

We had a scare with Trifexis also. Gypsy is an inside dog and has never had seizures......until the last time I gave her a dose of trifexis. She had a seizure two days after taking the medication. I called my vet and they said to discontinue use of trifexis. (and that is the only medication she is on) Luckily she is back to normal and hasn't had any other episodes.

 

My three year old Collie took Trifexis for ten months and two days after a dose, she had a seizure - lasted approx. four - five mins. - the longest in my life. Her legs would not hold her up, motorized head movement - looking up a ceiling. Could not stand and i held her until it passed. In four days i took her back to vet.

 

My dog has been on this for a few months and on Thursday evening after we have it to him, he was breathing weird, stumbling, falling down, whining, and craning head to right. Muscles were very tense. He got better yesterday but this morning is acting weird again. This pill needs to be taken off the shelves!!! I feel terrible for not looking into it before giving it to him.

 

My dog has been on trifexis for 6 months. we gave her a dose on Wednesday (a new box and a higher dose due to her increased weight). By Thursday night she was suffering side effects (lethargic, not eating/drinking, twitching). We plan on taking her to the vet tomorrow. My question is, at this point is there anything the vet can do to help her? Thanks for the info.

 

Let's hope. It did no good for our Peaches, who would up at the emergency vet in Blacksburg at midnight, and perished there. I pray for your dog.

 

Can anyone tell me a safe, effective heartworm preventive medicine if Trifexis is bad?

Do not give your dog Heartgard without first having your dog tested for the MDR1 gene. Heartgard is safe generally, but not for dogs with that gene, and its typically herding breeds that can have it.

 

Go to heartworm society website for a prevalence map. the further east and south you go the worse it gets. PS, indoor dogs " that never go outside" can still get heartworm as mosquitos still end up indoors and it only takes one bite.

 

(end of quotes from the above link)

 

......anyone have any concerns or negative experiences with Triflexis ?

 

THEN I found a link where Border Collie owners have had their dogs have negative reactions to Heartguard -

 

http://www.earthclin...e_effects2.html

 

(some of the quotes from the above link)

 

Julee Johnson from Medina, Ohio, Usa: "I read on here that a women's Border Collie had seizures when her dog was on Heart Guard. I do not keep my Border Collie mix on Heart Guard year round. She has had three seizures that I have witnessed over the years. I went through her records and she was on Heart Guard at the time of all three seizures. I don't think I'll put her back on it and I'll be curious to see if she has anymore."Replies

Doug from San Antonio, Texas replies: "Ivomectrin should not be used on Border Collies it absolutely causes siezures. We chose Advantage Multi based on research and advice from several other Border Collie owners. Our two year old Border Collie has had no problems with Advantage Multi."
 

Michael from Chilliwack, B.c. Canada replies: "Ivermectin destroyed maggie's nerves... (my first border collie)...."
 

(end of quotes)

 

......what is the proven safest alternative to Triflexis ?

 

(perhaps we should do a poll with all the medications listed to see how many owners uses each brand without noticing any negative reactions)

[Gideon's girl]

All monthly heartworm preventions are from the same class of drugs and can affect dogs that are sensitive.  The incidence of Border Collies being affected are very low, however, you should use the lowest dose possible and all monthly heartworm preventions are actually good for 45 days.  They just suggest using them on the same day of the month for ease of memory. 

 

Dogs that have shown to be prone to seizures should be exposed to any chemicals as absolutely as little as possible.  Seizures are considered a threshold event.  When a dog reaches it's threshold it will have a seizure.  Reducing chemical load and other stressors helps to keep the dog further away from it's threshold.

[Gary_and_Karen]

Thanks for your insight.

 

Our dog is about 39-40 lbs so we had her on the "green" Triflexis which covers from 20.1 to 40 lbs and was giving it to her the first of the month, but I am still leary about giving her any more after reading all those sad comments on that web site I posted.  

 

Our last dog was not on any regular ongoing meds and she survived healthy and perky for 15 years right up to her last day, so it makes me wonder if it is worth the risk to use ANY meds on a repetitive ongoing basis, what do you think ?

 

Is the risk of heartworm really that great to justify the risk of the dangers from the meds themselves ?

 

As far as being prone to seizures, how can you know until it actually happens, and why risk it happening if certain meds have been shown to have a tendency to cause it ?

 

I'm not trying to sound negative, I just want to be very careful after reading what other dog owners went thru after giving their dogs such meds.

 

Also, I'm not sure if our dog being a Border Collie / Beagle mix could make a difference in how the meds could eventually affect her.

 

 

All monthly heartworm preventions are from the same class of drugs and can affect dogs that are sensitive.  The incidence of Border Collies being affected are very low, however, you should use the lowest dose possible and all monthly heartworm preventions are actually good for 45 days.  They just suggest using them on the same day of the month for ease of memory. 

 

Dogs that have shown to be prone to seizures should be exposed to any chemicals as absolutely as little as possible.  Seizures are considered a threshold event.  When a dog reaches it's threshold it will have a seizure.  Reducing chemical load and other stressors helps to keep the dog further away from it's threshold.

 

 

All monthly heartworm preventions are from the same class of drugs and can affect dogs that are sensitive.  The incidence of Border Collies being affected are very low, however, you should use the lowest dose possible and all monthly heartworm preventions are actually good for 45 days.  They just suggest using them on the same day of the month for ease of memory. 

 

Dogs that have shown to be prone to seizures should be exposed to any chemicals as absolutely as little as possible.  Seizures are considered a threshold event.  When a dog reaches it's threshold it will have a seizure.  Reducing chemical load and other stressors helps to keep the dog further away from it's threshold.

[Beach BCs]

With every medication there are risks. I don't use Trifexis, yet.I have been using Interceptor and Comfortis, which I believe is more or less what Trifexis is. (I was lucky to purchase a significant amount of Interceptor when she shortage came about.) There are other HW meds out there. Maybe do some research and find another you are more comfortable with. But I wouldn't risk taking your dog off of a monthly preventative. Just my .02.