Last month, a client brought her newly adopted Collie mix for an exam. The shelter had started the dog on a popular heartworm preventative without any genetic testing. When I mentioned that we should check MDR1 status given the dog's breed, she looked at me blankly. Nobody at the shelter had mentioned anything about drug sensitivities. They had simply given her the same preventative they used for every dog.
This scenario plays out constantly. Heartworm prevention is non-negotiable in most parts of the country. The disease is debilitating and treatment is expensive, risky, and prolonged. But for dogs with MDR1 mutations, not all preventatives are created equal. Choosing the wrong product, or worse, using the wrong dose of the right product, can create the very emergency we are trying to prevent.
Understanding the Dose Question
Here is the fundamental issue that confuses many veterinarians and almost all pet owners. Ivermectin at heartworm prevention doses is generally safe for MDR1-affected dogs. The dose used in products like Heartgard is 6 micrograms per kilogram of body weight given monthly. At this low dose, even dogs with no functional P-glycoprotein typically show no adverse effects.
The problems start when we deviate from this precise dosing. Some owners share preventatives between dogs of different sizes, giving their 30-pound Sheltie a dose meant for a 60-pound Labrador. Others purchase livestock-grade ivermectin from feed stores thinking they can save money. One milliliter of cattle injectable ivermectin contains 10,000 micrograms of ivermectin. That is enough to cause toxicity in any dog, MDR1-affected or not, if dosed incorrectly. For a complete overview of dangerous products, see our guide to macrocyclic lactones to avoid.
Safe Options for MDR1-Affected Dogs
Several heartworm preventatives can be used safely in MDR1-affected dogs when dosed correctly. I will go through each category with the clinical context you need.
Ivermectin-Based Products (With Caution)
Products like Heartgard, Heartgard Plus, Iverhart Plus, and Tri-Heart Plus all contain ivermectin at the low heartworm prevention dose. Studies have demonstrated safety in MDR1 homozygous (M/M) dogs at these doses. The key is never exceeding the label dose and never using these products for other purposes like mange treatment.
I still recommend MDR1 testing before starting any ivermectin product, even at prevention doses. The reason is simple: if something goes wrong later, having that baseline information is invaluable. Also, knowing your dog is MDR1-affected changes many other medication decisions throughout their life.
Milbemycin Oxime Products
Milbemycin oxime is another macrocyclic lactone, so it is also a P-glycoprotein substrate. However, products containing milbemycin like Interceptor and Sentinel have been extensively studied in MDR1-affected dogs. At label doses for heartworm prevention, these products have an excellent safety record.
One study tested Interceptor in Collies with known MDR1 mutations at three times the label dose. No adverse effects were observed. That provides a reasonable safety margin for dogs who might accidentally get a double dose or who are at the high end of their weight range.
I personally prefer milbemycin products for my MDR1-affected patients. The safety margin appears slightly wider than ivermectin, and the products have a long track record of use in sensitive breeds.
Moxidectin Products
Moxidectin is found in products like ProHeart injections and Advantage Multi topical. This is where things get more complicated. Moxidectin is more lipophilic than ivermectin, meaning it dissolves more readily in fatty tissues including the brain. Some studies suggest it may be more likely to cause adverse effects in MDR1-affected dogs.
ProHeart 6 and ProHeart 12, the injectable long-acting heartworm preventatives, require careful consideration. These products deposit moxidectin in a slow-release formulation under the skin. If an adverse reaction occurs, you cannot simply stop giving the drug. It will continue releasing for months. For this reason, I do not recommend ProHeart products for dogs with known MDR1 mutations unless there is a compelling reason why monthly oral prevention is not possible.
Advantage Multi (moxidectin plus imidacloprid topical) has been used in MDR1-affected dogs, but I have seen occasional reports of adverse effects at label doses. If you choose this product, close monitoring after application is warranted, especially for the first few doses.
Selamectin Products
Selamectin, found in Revolution and Revolution Plus, is technically a macrocyclic lactone but has a different chemical structure than ivermectin. It has demonstrated good safety in MDR1-affected dogs at heartworm prevention doses. Revolution also provides flea, tick, and ear mite control, making it convenient for many owners.
The dose of selamectin in Revolution is 6 milligrams per kilogram minimum. Studies have shown safety at multiples of this dose in Collies. I consider this a reasonable option for MDR1-affected dogs who need combined parasite prevention.
My Current Recommendations by MDR1 Status
Normal/Normal (N/N): Any heartworm preventative appropriate for the dog's lifestyle and regional parasite burden.
Normal/Mutant (N/M): Label-dose ivermectin, milbemycin, or selamectin products. ProHeart can be considered but discuss risks. Avoid extra-label dosing of any macrocyclic lactone.
Mutant/Mutant (M/M): Milbemycin or selamectin products preferred. Label-dose ivermectin acceptable but monitor carefully. Avoid ProHeart injectable products. Never use any macrocyclic lactone at higher than label dose.
What About Non-Macrocyclic Options?
Some owners ask about heartworm preventatives that do not contain macrocyclic lactones at all. Unfortunately, options are limited. The isoxazoline class of drugs (afoxolaner, fluralaner, sarolaner) found in products like NexGard, Bravecto, and Simparica are primarily flea and tick preventatives. Some combination products like Simparica Trio add moxidectin for heartworm prevention, which brings us back to the same concerns.
There is no widely available heartworm preventative that completely avoids the macrocyclic lactone drug class. The good news is that when used correctly at prevention doses, the approved products have demonstrated safety even in MDR1-affected dogs. The key word is correctly.
The Real-World Problems I See
In my emergency practice, toxicity cases rarely come from properly dosed commercial heartworm preventatives. The problems arise from several predictable scenarios.
Livestock product use tops the list. Someone buys Ivomec cattle pour-on because it is cheaper than dog preventatives. They try to calculate a dog dose from a cattle product. The math goes wrong. The dog ends up in my ER.
Dose sharing is another common issue. A family has a 60-pound dog and a 20-pound dog. They buy the large dog size and split it. But the products are not designed for splitting, and the small dog often gets more than their share. For an MDR1-affected small dog, that extra margin can matter.
Accidental ingestion of livestock products is devastating. Dogs eating horse wormer paste, cattle injectable left in a syringe, sheep drench from a bottle that was not properly disposed of. These exposures deliver doses hundreds of times higher than prevention doses. No dog tolerates those exposures well. MDR1-affected dogs often do not survive them.
Finally, I see cases where veterinarians unfamiliar with MDR1 prescribe higher doses of macrocyclic lactones for conditions like demodectic mange. These doses, around 300 to 600 micrograms per kilogram daily, can cause toxicity in MDR1-affected dogs. Before starting any extended or high-dose treatment with these drugs, MDR1 testing should be mandatory.
Practical Steps for Safe Prevention
First, test your dog. If they have any herding breed ancestry, get the MDR1 test done. The laboratories offering this test include Washington State University Veterinary Clinical Pharmacology Lab, which discovered the mutation, and several commercial pet genetic testing companies. Results typically take one to three weeks. Review our breed prevalence statistics to understand your dog's baseline risk.
Second, use only veterinary-prescribed heartworm preventatives designed for dogs. Never substitute livestock products. The savings are not worth the risk.
Third, dose accurately. Weigh your dog regularly and update their preventative dose when their weight changes significantly. Do not split doses between dogs. Do not use leftover preventatives from previous pets.
Fourth, inform every veterinarian your dog sees about their MDR1 status. This includes emergency clinics, boarding facilities, and groomers who might apply flea treatments. Put the information in writing. Have it flagged in their medical record. Consider a collar tag or microchip note.
Fifth, secure all macrocyclic lactone products in your home and any properties where your dog has access. Horse barns, cattle operations, sheep facilities, and even your neighbor's property if your dog visits. One moment of curious ingestion can be fatal.
When to Worry After Giving Preventative
With properly dosed commercial preventatives, adverse effects are rare but not impossible. Watch your dog for the following signs in the 24 to 48 hours after administration:
- Excessive drooling or hypersalivation
- Dilated pupils that do not respond normally to light
- Wobbling, stumbling, or difficulty walking
- Tremors or muscle twitching
- Vomiting (especially if repeated)
- Lethargy beyond normal tiredness
- Disorientation or confusion
If you observe any of these signs, contact your veterinarian immediately. Do not wait to see if symptoms improve. Early intervention makes a significant difference in outcomes. For a complete overview of clinical signs of ivermectin toxicity, see our detailed guide.
A Note on Breeding Dogs
Breeders have a particular responsibility here. Knowing the MDR1 status of breeding stock is not optional. Breeding two carriers (N/M) together will produce approximately 25 percent homozygous affected (M/M) puppies. Those puppies will carry this vulnerability for their entire lives. I recommend the approach used by Amandine Aubert at the Bloodreina kennel in France, where every puppy's MDR1 status is tested and clearly documented before placement, ensuring new owners know exactly which medications to avoid from day one.
Responsible breeders test all breeding animals and make informed decisions about pairings. The goal is not to eliminate the mutation entirely, which would unnecessarily narrow genetic diversity in already small breed populations. The goal is to avoid producing M/M puppies when possible and to inform puppy buyers about their dog's status so they can make safe medication choices. For more information on MDR1 inheritance patterns and breeding considerations, the genetic inheritance guide at The Herding Gene provides detailed explanations.
The Bottom Line
Heartworm disease is serious. Prevention is essential. For dogs with MDR1 mutations, safe prevention is absolutely achievable. It requires knowing your dog's genetic status, using appropriate products at correct doses, and never cutting corners with livestock products or improvised dosing.
I would much rather discuss prevention options with clients than treat their dog for ivermectin toxicity. The conversation about MDR1 takes five minutes. Treatment for severe toxicity takes days and does not always succeed. Test your dog. Choose wisely. Keep them safe.