My personal quest to find the safest parasite protection for dogs known to carry the MDR1 (Multi Drug Resistance) gene led me on a merry chase. MDR1 is a drug sensitivity that affects the majority – approximately 70%-75% of Rough and Smooth Collies in the USA and potentially worldwide. (There are 13 other at-risk breeds including Border Collies, Australian Shepherds, German Shepherds, Shetland Sheepdogs, and Old English Sheepdogs, plus herding breed mixes.)
The lack of accessible information on the topic of safe parasite protection for dogs with the MDR1 gene (Multidrug Resistance gene) left me so frustrated that I decided to write my own article. So here’s the culmination of my research: information gathered from laboratory case studies, veterinarians, and Collie owners, breeders, and exhibitors. It was somehow both boring and interesting work, but it yielded helpful information.
I have an Aussie mix, plus three Rough Collies who have 1 copy of the MDR1 gene (carriers/mildly affected), so I have a vested interest in everything I’ve researched. I’ll list products I’ve looked into – several of which I’ve personally tried – along with whether they’re generally considered safe to use or should be used with caution. Technically, they’re all supposed to be safe, but some products are undoubtedly better and more consumer-trusted than others. (Follow this link for official problem drugs.)
If you’re hoping for a quick, easy skim and just want to know which pest protections are rated safest and best, I’ll give those first under each category. In fact, in full expectation most people will skim, I repeat myself a lot. Sincere apologies to those who read this article start to finish… But hey, repetition is the key to retention, right?
This is not an exhaustive listing of every product out there, but it will provide tools to identify which meds are related to each other or essentially the same as major brands. It’s all based off active ingredients. For instance, Heartgard’s main ingredient is Ivermectin, so any product containing Ivermectin falls under the same category. If you want to know about a specific product, read the active ingredients on the front of the box and compare to one of the products listed in this article. Or check the 100+ comments below this post!
For those who want more in-depth information, I’ve created embedded links throughout for further reading. (Some of the links lead to peer-reviewed scientific articles, so have fun with those if you want the bare, dusty facts.)
Disclaimer: even parasite protection products officially labeled safe – for an MDR1 dog or any dog – should really be designated “safe-ish.” But parasite preventives are chemical compounds – some of which are used in pesticides – and thus have more potential to cause a reaction than just, well, water. Any dog can be sensitive to a certain substance and should always be monitored for reactions after a new product has been administered. However, Collies and associated breeds, with or without an MDR1 status (officially the AbCb1 gene), simply have a reputation for being generally sensitive and prone to side effects from parasite preventives.
I’ll also discuss organic topicals I’ve found somewhat effective as repellents. Unfortunately I have not learned of any natural pest control products as effective as chemical-based ones. This article from Your Dog Advisor gives natural prevention options and explains how to mix your own parasite preventives using essential oils. However, dogs can also be sensitive to essential oils – like my friend who is allergic to lavender – so “natural” doesn’t automatically mean “best” for your dog either. You should still keep an eye on your pet when introducing new organic products.
Heartworm Preventive / Treatment
Bear with me for a little pharmaceutical science, which I promise is important and will make sense in the end! It’s simpler to identify medicines by their components. Some are nearly the same thing marketed under different brand names.
All the available heartworm medications on the market are a variation of what is known clinically as a ML (macrocyclic lactone) compound. These four ML compounds (ivermectin, moxidectin, selamectin, and milbemycin oxide) have been officially approved by the FDA (Federal Drug Administration) and tested safe for MDR1 dogs when administered at the recommended preventative dosage.
However, not all ML’s are created equal, and some are safer than others. If an MDR1-affected dog were to be treated for mange, that would involve higher dosages and could cause adverse reactions. Another danger often lies in a treated dog being exposed to additional environmental pesticides, which can lead to an accidental overdose.
Regardless of the heartworm product you choose, as the Institute of Pharmacology and Toxicology says, “treatment of MDR1 mutant dogs with macrocyclic lactones in general requires particular caution.” It really boils down to weighing the benefits of medications against the risks from internal parasites.
TOP PICK
Interceptor Flavor Tabs (milbemycin oxime)
Interceptor, which comes in a monthly chewable form, has been specifically tested and approved for dogs with MDR1. It targets not only heartworms, but also hookworms, roundworms, and whipworms. Additionally, it can also be given to cats and even pregnant or nursing animals.
Interceptor is the go-to heartworm preventive for many Collie parents. I polled an international forum for Collie lovers – the breed with the highest occurrence of MDR1-affected dogs – about which heartworm medication they preferred. Out of 67 respondents, 48 said they used Interceptor, with no side effects reported.
Some veterinary clinics stock it for their clients, and it is also available at online stores like 1-800-PET-MEDS or Chewy. I save money buying the generic Milbeguard. (If you order online, keep in mind that the company will first need to contact your veterinarian for a prescription to be issued.)
According to a thorough study conducted on MDR1-affected dogs, Interceptor ranked high in ML safety due to its use of the compound called milbemycin oxime. Documented negative reactions were only provoked at higher-than-normal dosages and were comparatively mild, consisting of salivation, ataxia (dilated pupils), and depression.
The amped-up version, Interceptor Plus, also contains praziquantel, which is used to treat tapeworms. However, the safety of Interceptor Plus has not been evaluated for pregnant or lactating dogs, and it is not recommended for cats. Negative reactions such as vomiting, diarrhea, and tremors were only observed at supratherapeutic (higher than recommended) doses. But unless your dogs have had a problem with tapeworms (whose segments are visible to the naked eye in dog’s poo), then the regular Interceptor should be fine.
USE CAUTION
Heartgard Plus (ivermectin/pyrantel)
Probably the most well-known heartworm medication is Heartgard, which contains Ivermectin. Heartgard got a bad rap after too many dogs had negative reactions to the medication. With complaints rolling in, the company made adjustments to the Ivermectin content in their product, and Heartgard is now advertised as “safe at the recommended dosage.” But according to Dr. Judy Morgan, “Neurologic side effects are a possibility with Heartgard.”
The Whole Dog Journal notes that “Ivermectin has the most potential for toxicity.” As mentioned above, polling a Collie lovers’ forum showed that only 9 of 67 people used Heartgard, and another 5 people said their dogs had a bad reaction to it. One woman even said her Sheltie died after being given Heartgard.
Anecdotally, other veteran Collie breeders and owners have horror stories of even MDR1-clear Collies displaying adverse reactions to meds containing Ivermectin. They won’t recommend “harsh” medications such as Heartgard for any Rough Collie, Smooth Collie, or other breed prone to MDR1. Even if a genetic test reveals a dog to be normal/normal (clear) of the MDR1 gene, it seems these breeds are just more likely to show medication side effects.
There are other risks involving Ivermectin. A dog on Heartgard may – because dogs can be gross – eat the feces of an animal who was given an Ivermectin-based medication. For dogs who have a case of mange or ear mites, the treatment can involve topical applications of compounds containing (you guessed it) Ivermectin. Any of these scenarios can cause unintended overdoses. Bottom line: it’s best to avoid giving your Collie Heartgard or a similar medication. There are definitely better options.
Several Heartgard knockoffs are available such as Tri-Heart Plus, Iverhart Plus, and Nuheart. Because of their similarity to Heartgard, I’ve placed them in the same “caution” category. There is also an injectable product called Pro-Heart, a shot that lasts for 6 months. It’s a very appealing option, but still not one I will recommend due to its high Ivermectin content.
Combination Medication (Internal/External Parasites)
The parasite protections that target multiple parasites with just one topical application or administration of a pill are extremely appealing due to their convenience. The drawback of using them is that they generally don’t take care of as large a range of parasites as using two separate medications does.
In particular, though some of these combination medications do cover ticks, none specifically target the blacklegged ticks which carry Lyme Disease. If you use a combo internal/external parasite preventive, consider asking your vet about a Lyme Disease vaccination. This is less of a concern if you don’t walk your dogs through woodsy areas in a region where these ticks are prevalent.
TOP PICK
Revolution (selamectin)
Revolution, along with a product called Stronghold, tested safest in clinical trials of heartworm medications. Selamectin is their shared main ingredient. Revolution and Stronghold even tested safe over the recommended monthly dosage for dogs with the MDR1 gene, and they hold the distinction of being the only heartworm meds that did not produce any negative drug reactions.
Revolution is also an attractive option due to its ease of application (topical squeeze-on tube) and versatility against heartworm, fleas, dog ticks, sarcoptic mange, and even ear mites.
*Important note: since Revolution does not protect against blacklegged ticks, ask your veterinarian about getting a Lyme Disease vaccine.
GOOD PRODUCT
Sentinel (milbemycin oxime/lufenuron)
Sentinel comes in a chewable pill form and protects against multiple internal parasites (heartworms, whipworms, hookworms, and roundworms) as well as the development of flea eggs. One downside of this medicine is that it will not eliminate adult fleas – or any ticks. Sentinel has been referred to as “flea birth control.” You may want to use it in combination with products like Capstar or an insect repellent spray. (More on those later.)
From a safety standpoint, this is a pretty good product. But be aware of its limited coverage of external parasites and non-endorsement for pregnant or nursing female dogs.
USE CAUTION
Advantage Multi (moxidectin/imidacloprid)
A strong medication, Advantage Multi is a spot-on treatment targeting heartworms, whipworms, roundworms, hookworms, and adult fleas. Additionally, it can be used to treat and control sarcoptic mange. Unfortunately, it does not cover any ticks.
Moxidectin, the heartworm-fighting portion of Advantage, is considered safe if the proper dosage is given monthly, but it did not test as well as either selamectin or milbemycin oxime in clinical trials, though it ranks above Ivermectin.
Studies have shown that the way an ML (macrocyclic lactone) is administered to an MDR1-positve dog makes a drastic difference in how it affects them. For instance, some ML’s are best tolerated when orally ingested, which meant that a pill form of that particular compound was developed; but moxidectin was just the opposite.
As noted in an article by Dog Aware: “Advantage Multi, which combines imidacloprid for flea control with moxidectin for heartworm prevention, was found to cause no side effects when applied topically to affected dogs even at 5 times the recommended dose, but ingesting less than half the recommended topical dose caused extreme toxicity leading to coma in four of five dogs.”
With Advantage Multi, great care should be taken to only apply the liquid between a dog’s neck and shoulder blades, where it cannot be reached by licking. Children should be kept away from the dog for 2 hours until the liquid has had time to dry, and hands should be washed after application. You might want to pick a different parasite preventive if you have more than one dog. Herding breeds in particular like to “herd” each other by gnawing on the backs of their necks!
USE CAUTION
Trifexis (milbemycin oxime/spinosad)
Trifexis is perhaps the most well-known (and frequently peddled at veterinary clinics) of this combo category. It is easily administered since it is a flavored chewable, and it takes care of heartworms and fleas. On the downside, it does not cover any ticks. If you’re someone who lives in a tick-prone area or likes to take your dogs on woodland rambles, this is a letdown.
According to the product description, side effects as a result of Trifexis are rare, but can be as severe as seizures or even a coma. While this study conducted on twenty MDR1-affected Collies did not reveal any adverse reactions when the dogs were given low doses of Milbemycin Oxime combined with Spinosad, the Washington State University of Veterinary Medicine does advise that “some of the combination flea+heartworm preventive products (those containing spinosad) should be used cautiously in dogs that are MDR1 mutant/normal because of a risk of serious drug-drug interactions.”
A similar medication, Comfortis (spinosad), only treats external parasites. But I’ve given it a “caution” designation as it is not safe for dogs at risk for seizures.
Flea & Tick Prevention: Oral
GOOD PRODUCT
Capstar (nitenpyram)
Capstar specifically targets adult fleas, so it is best paired with a product like Sentinel. It comes in pill form, starts working within 30 minutes, and will kill all the adult fleas on a dog within 4 hours. Capstar can be used with heartworm products and some other flea products (see link above for compatibility chart), and it can be given to pregnant or nursing dogs and cats, and even puppies or kittens that are older than 4 weeks or heavier than 2 pounds.
On the downside, its efficacy only lasts for about a day, it doesn’t target ticks, and it is definitely not cost-effective. Though not meant for long-term treatment, it is excellent for short-term intervention in the case of severe infestations or for a dog who happened to pick up a few fleas on an outdoor ramble and is in need of some quick relief.
SOME CAUTION
Credelio (lotilaner)
Credelio is a relatively newer medication released in January 2018 by Elanco, the same company that makes Interceptor. It is safe for use with anthelmintics like heartworm meds and has no known negative drug-drug interactions. I love that it quickly kills adult fleas and four kinds of ticks: American dog tick, brown dog tick, lone star tick, and black-legged ticks – which carry Lyme Disease. Before being approved by the FDA and released to the public, clinical trials were performed on Beagles (a breed prone to seizures) and Collies (prone to MDR1).
Credelio stands out from the other three members of its class by using the active ingredient lotilaner. It was uniquely formulated with more reaction-prone breeds in mind. Still, as an isoxazoline it is technically in the same family as Nexgard, Bravecto, and Simparica.
Credelio had very few (6 reported seizures in as many months) negative reports submitted to the FDA at the time; but it was still required to add a precaution to its label because a) its main ingredient is in the “-laner” family, and b) it is a newer product with a lower usage rate. As the agency explained: “Although FDA scientists carefully evaluate an animal drug prior to approval, there is the potential for new information to emerge after marketing, when the product is used in a much larger population.” (New drugs continue to be highly monitored for the first three years following their release.)
My veterinarian specifically recommended Credelio as a safer option for my MDR1-heterozygous (mutant/normal) Collies with flea allergies. (The mutant/normal designation means a dog has one copy of a gene and is a carrier, though not affected to the degree that a homozygous, or mutant/mutant, dog would be.)
Since the Credelio medication can be passed through a mother’s milk, it is not recommended for pregnant or nursing female dogs. However, it is safe for puppies 8 weeks of age and older. Like any oral medication, It should be given with food to avoid a possible upset stomach.
MORE CAUTION
Nexgard, Bravecto, Simparica (isoxazolines)
In September of 2018, the FDA issued a warning to all users of Bravecto (fluralaner), Nexgard (afoxalaner), and Simparica (sarolaner). Though all of these medicines had previously been approved by FDA scientists, now “data received by the agency… indicates that some animals receiving Bravecto, Nexgard, or Simparica have experienced adverse events such as muscle tremors, ataxia, and seizures.”
Regarding seizures specifically: at that time Nexgard averaged 263 reported per year, Simparica averaged 186 reported per year, and Bravecto averaged 180 reported per year.
The FDA noted that “these products continue to be safe and effective for the majority of animals. The agency is asking the manufacturers to make the changes to the product labeling in order to provide veterinarians and pet owners with the information they need to make treatment decisions for each pet on an individual basis.”
While the FDA did not pull these drugs from the market, it asked the product manufacturers to add precautions to their labels while it continues to monitor information submitted by veterinarians, the companies themselves, and individual product users. The FDA alert regarding the medications in the isoxazoline class of drugs was still in effect as of 2021, and likely will remain in effect.
In light of this, I’m categorizing all three of these oral flea/tick protection chews as “use with caution.” A link between the occurrences and seizure-prone or MDR1 dogs has not been identified.
MOST CAUTION
Nexgard (afoxalaner)
Though I already mentioned Nexgard as being included in the FDA statement, I’m dealing with it separately because it is such a well-known product. It is also frequently used in combination with Heartgard and other anthelmentics, which can be risky, due to potential negative drug-drug interactions. Most pet parents give heartworm medications in conjunction with flea & tick medications, so I’d have given Nexgard a “caution” label even before the FDA warning came out.
While Nexgard had the highest number of seizures reported annually, it may be related to being used with other drugs. I also wonder if it has a higher usage rate, but I don’t have the number of annual sales in relation to the other two popular products. Personally, I won’t recommend it.
Dr. Judy Morgan described the case of a Beagle brought to her that was suffering from seizures, which were likely the result of or worsened by being wrongly prescribed Nexgard in combination with another medication. Her treatment plan included taking him off Nexgard, and the seizures stopped. Dr. Morgan concluded her story with: “Be your pet’s advocate. If the veterinary staff can’t see they are prescribing the wrong combination of medications, maybe you can point it out to them.”
Flea & Tick Prevention: Topical
These can come in a few different forms: monthly spot-on, a disposable collar, or a spray. The Whole Dog Journal points out that “oral flea-control medications have been proven to be more effective than topical pesticides in both killing fleas and helping to control a household infestation more quickly.” While this is true, the benefit of topical treatments is in their general safety.
However, as with any chemical compounds, caution is advised even with products deemed to be safe. According to Dog Aware, most “flea and tick control medications have not been found to cause adverse effects when used as directed, but toxicity can occur if topical products are ingested.” This is why reading labels is so important. If a spot-on treatment is applied between the neck and shoulders as directed, no harm should befall a dog; but if it’s applied past the shoulders where a dog can reach with its tongue, that could definitely cause problems.
TOP PICK
Advantage II (imidacloprid/pyriproxyfen)
Advantage takes care of fleas at all life stages and is even supposed to kill them on contact, and it also covers lice. It is approved for use on puppies at least 3 pounds in weight and 7 weeks of age, cats, and even ferrets. As with any topical product, monitor your pet for signs of skin irritation, and give them a bath within 24 hours to wash it off if signs of irritation are seen. After 24 hours, it is considered waterproof and a bath, while alleviating some effects, will not offer as much relief.
The drawback of Advantage is that it does not offer any protection against ticks. If you’re living in an urban setting, this product could still be a good option for you, as you’re not likely to encounter many ticks in a concrete jungle. For those who like Advantage but are concerned about ticks on their dogs, the Preventic Tick Collar can be worn for additional protection. (Just bear in mind that Preventic contains amitraz, which is toxic to cats.)
GOOD PRODUCT
Frontline Plus (fipronil/s-methoprene)
Frontline Plus targets four kinds of ticks, fleas (including eggs and larvae), lice, and mites that cause sarcoptic mange. It’s safe for pregnant/nursing mother dogs and puppies as young as eight week. After talking to a variety of Collie people, Frontline seems to be the most trusted of the topical flea/tick products available. Anecdotally anyway, it is reported to have gentler ingredients and the least tendency to cause skin irritations.
An added benefit is it has been around long enough that cheaper generic products are available, some of which I’ve tried and found to be as effective as Frontline. (One such knockoff, Pet Armor Plus, is even available at Walmart.)
Unfortunately, the fleas are fighting back. Some parts of the U.S. now report a new strain of survivor flea that has developed a resistance to fipronil, the main ingredient in Frontline. If you live in an area where the fleas just refuse to die, you may want to consider an alternative, stronger product.
GOOD PRODUCT
Natural Chemistry (cinnamon, clove, cedarwood oils)
For anyone who prefers to use organic instead of chemical products or would like a repellent in addition to what you are already using, this is the flea and tick spray for you! It will make your dog smell absolutely yummy while protecting them from fleas, ticks, black flies, and mosquitoes. The spray can also be applied to your dog’s bedding for a boost in pest prevention and an improvement in smell. Natural Chemistry claims to kill on contact and to be safe for puppies.
The key to getting this spray to work well is to apply it well (rub against the lay of the coat while spraying the roots of the hair to get down to the skin); thoroughly (to the underbelly, legs, and paws); and often (at least once a week, more if your dog gets wet). While I didn’t find it quite as effective as the label says, that might have something to do with living in pest-ridden Florida and having heavy-coated dogs. Honestly, I’d use it as a deodorizer even if it was completely ineffective against parasites.
GOOD PRODUCT
Diatomaceous Earth (fossil shell flour)
This organic powder is great for a variety of uses. Some swear by food grade DE (diatomaceous earth) as a natural dewormer of roundworms, hookworms, whipworms, and even tapeworms. However, it will not affect heartworms at all, since they do not infest the gastrointestinal tract.
It can be used to destroy bedbugs, cockroaches, ants, and even fleas. I like to sprinkle some around the perimeter of my yard and lay an inner circle around the edges of my house – which probably looks like I’m trying to keep out evil fairies and other fantasy creatures. You can even scatter some on your dog’s bed. DE works best when dry, and its effectiveness will be reduced after it gets wet.
Rich Soil gives this excellent explanation of what DE is and how it works:
“…the fossilized remains of marine phytoplankton. When sprinkled on a bug that has an exoskeleton (such as bed bugs, ants or fleas) it compromises their waxy coating so that their innards turn into teeny tiny bug jerky. But it doesn’t hurt mammals. We can eat it. We do eat it! It’s in lots of grain-based foods because lots of grains are stored with diatomaceous earth to keep the bugs from eating the grain.”
EXTREME CAUTION
Seresto (imidacloprid/flumethrin)
The best thing about Seresto is how long it can do its job – up to 8 months! It is formulated to repel and kill fleas and 4 kinds of ticks on contact, provide protection from lice, and treat/control sarcoptic mange. The collar releases no odor or residue, comes with a quick release catch to prevent accidental choking, and even has safety reflectors. Though water resistant, frequent bathing or swimming (once a month or more) will reduce the collar’s effective time to 5 months or less.
However, I won’t recommend Seresto collars. It is now known that they have caused seizures and death in dogs and even some reactions in humans who sleep with their dogs in their beds. (This is for all dogs, not just for dog breeds at-risk for MDR1.) From the time that the collar went on the market in 2012 until 2020, the EPA (Environmental Protection Agency) received 1,698 reports of deceased pets. That averages out to about 212 deaths per year. Not a high number? Sure. But dead is dead.
Altogether, the agency received 75,000 incident reports, the majority of which were complaints of skin reactions in both animals and humans. I’ve talked to Collie and Aussie owners who absolutely swear by their Seresto collars and others who are livid because they made their dogs’ neck bald!
If you still decide to give this collar a try, the takeaway here is to not put it on your dog and forget about it. As with everything else, monitor your dog for symptoms. The majority of canines will be fine, but there are enough who will react. Unfortunately, it seems most people who lost their dogs to Seresto collars simply did not make the connection until it was too late.
If Seresto seems to be negatively affecting your dog, remove it and bathe the dog (paying particular attention to the neck area) with a gentle shampoo and multiple rinses.
USE CAUTION
K9 Advantix II (imidacloprid, permethrin, pyriproxifen)
This product has the distinction of repelling and killing fleas (at all life stages), ticks, lice, mosquitoes, and even repelling biting flies. Unlike many other external parasite treatments that only kill little bloodsuckers after they’ve bitten the dog, K9 Advantix claims to kill them on contact. A product this strong may not be best for a dog that has sensitive skin issues, as irritation can develop at the site of application. To help with this, the product can be applied in more than one line between the neck and shoulder blades.
Since Collies and cats go together so well, I have to include this caution for cats: “Some ingredients used to kill ticks, such as permethrin (used in K9 Advantix and other products) and amitraz (used in Certifect and the Preventic collar), are toxic to cats, which can be a problem in a household that includes both, especially if they are friendly with each other.” If you have cats that share sleeping space with and/or like to groom your dogs, Advantix is probably not the best product for you. The back label warns that it “may be fatal” for cats, and advises cats and dogs should be kept apart for 24 hours following application.
EXTREME CAUTION
Vectra 3D (dinotefuran, permethrin, pyriproxifen)
This product is not recommended for MDR1 dogs, as its main ingredient, dinotefuran, is a harsh pesticide. Also, it is not recommended for use with other medications. Vectra’s brag is that it repels and kills fleas, five kinds of ticks, flies, mosquitoes, and mites; however, its use is not worth its risk. If you’re looking for something that will repel parasites, a product such as K9 Advantix II may make a good alternative.
As one holistic veterinarian explains: “The Vectra 3D can have side effects which include extreme restlessness and jitteriness, described as anxiety or manic behavior. The product insert states ‘Do not use this product on debilitated, aged, medicated, pregnant or nursing dogs, or dogs known to be sensitive to pesticide products‘.”
One final bit of advice
If you live in a seasonal region where you actually experience winter complete with freezing temperatures and snow, and your pets have been on regular pest prevention products, consider giving them a break from chemicals for a few months while the insects are dormant. But that is a personal judgment call.
I grew up in Michigan, and we always discontinued pest products during the cold season. In places where temperatures fluctuate enough for insects to come out of dormancy in winter (generally over 50° F or 10° C), be careful. If your dogs are exposed to untreated or wild animals who can carry fleas through the winter months, be careful. Otherwise, it may not be necessary to give parasite protection to your pets year round.
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I tried to review a variety of the most well-known parasite protection products out there. If I left out any you are curious about, check the active ingredients against products in the same category that were discussed above. Also, check the comments section. Chances are your question will be answered in the 120 comments below!
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