Injectable Heartworm Preventative Study

As a veterinarian with nearly 60 years of experience, I have witnessed the painful and deadly effects of heartworm disease in dogs. While many of my integrative colleagues are skeptical of prescription preventatives, I believe that heartworm disease is clinically worse than the potential adverse reaction to preventatives. Further, the preventatives have helped curb the epidemic proportions the disease could have become throughout the companion dog population.

Does stating this mean I do not have certain provisos or concerns? Not at all.

Two of my greatest concerns regarding heartworm preventatives are: 1). Parasitic resistance to the preventatives; and 2). Adverse events.

Short Heartworm Review

Heartworm disease is spread by mosquitos. The name is literal: they are parasitic worms that grow, can cause organ failure, and basically do this when they block the circulation through the heart and other blood vessels.

Heartworm Preventatives

Heartworm preventatives do not actually prevent mosquitoes from infecting your dog with heartworm larvae. These preventatives actually inactivate or kill the different stages of heartworm larvae that already have infected a companion dog. This is why we recommend giving heartworm preventives during the warm months of the year.

Dogs, cats and ferrets should be tested annually for heartworm disease. Companion pet parents that reside in the Southeastern United States should probably give the preventative year-round. States that experience cold weather months can adopt a 6-month protocol. Overall, the temperature needs to be above 57 degrees Fahrenheit for approximately two weeks and when mosquitoes are prevalent.

Currently, four preventatives are approved for companion dogs: milbemycin oxime, ivermectin, selamectin and moxidectin.

Plain oral milbemycin oxime (Interceptor®) is preferable as a heartworm preventive for certain groups of dogs, like sighthounds, smaller white breed dogs and those prone to seizures.

Plain ivermectin is known as Heartgard®.

Selamectin is a prescription topical (Revolution®) for dogs.

Moxidectin is commonly marketed and prescribed as a 6-month or 12-month injectable, ProHeart®. Advantage Multi® topical combines moxidectin with imidacloprid against fleas. Orally, Simparica Trio® consists of moxidectin, sarolaner (member of the isoxazoline class of drugs to prevent ticks and fleas on pets) and pyrantel (intestinal worm dewormer).

As you can see, there are not many approved heartworm preventatives in the toolbox. Unfortunately, heartworm larvae are slowly building a tolerance (resistance) to ivermectin and milbemycin oxime, respectively, particularly in certain pockets of the United States. This is one reason a 6-month oral protocol in cold weather states could be preferable.

Heartworm Study

Most often, animal pharmaceutical companies conduct research studies comparing the efficacy of their products to competitor products or to gain approval by the United States Department of Agriculture (USDA) or Food and Drug Administration (FDA).

It is rare to have an independent study conducted…particularly with heartworm preventatives.

Banfield Pet Hospitals – in association with Purdue University – reviewed its records from January 1, 2016 to December 31, 2020 seeking out dogs that potentially had an acute adverse reaction to the moxidectin injection, ProHeart®.

Banfield is a network of clinics owned by Mars Petcare, Inc. While the authors declare no conflict of interest, our review could not find a direct conflict of interest. Indeed, veterinarians at Banfield are giving the injectable and gave over a million doses during the reviewed timeframe.


Moxidectin is a newer heartworm preventative approved for companion dogs. The advantages of moxidectin are that it is more bioavailable than older generation preventatives, less heartworm parasite resistant at this time, and might be safer for dogs with the MDR-1 gene mutation.

Injections of Antiparasitic Drugs

Antiparasitic drug injections are not new or novel. Cattle often receive antiparasitic preventative injections of all formulations.

Study Premise

Adverse events involving heartworm preventatives for companion dogs can be voluntarily reported to the FDA and/or manufacturer by pet parents or veterinary professionals. As the study authors pointed out, there is the possibility of underreporting due to the voluntary status, traumatic degree of the event, and knowledge of how to report the events.

The incidence of adverse events with the 6-month product is estimated to be 3.9 events/10,000 doses based on data from 2008 to 2016.

The authors wanted to find out if the adverse events were potentially higher based on Banfield’s records.

Study Parameters

  • January 1, 2016 – December 31, 2020.
  • Canine visits to the veterinarian that included either the 6-month or 12-month sustained-release moxidectin product.
  • Excluded: Any visit when the dog also received a vaccination.
  • Based on that remaining pool, the authors looked at the percentage of dogs that had an acute adverse reaction within three days of product administration.

Adverse Events

An acute adverse event was defined as having met at least one of the following criteria within three days of product administration:

  • Diagnosis of allergic reaction, acute allergic reaction, urticaria (rash), anaphylaxis, immune-mediated disease, vaccine reaction (mild/localized, moderate systemic, severe systemic, or unspecified severity), dead on arrival, and death while under treatment.
  • Formal documentation of adverse reaction, which includes recording of any of the following 4 reactions: vomiting/diarrhea, swelling/hives/mass, anaphylaxis, or “other clinical signs.”


This study looked at trends. It did not name a cause or causes for the potential adverse events. That was not the purpose of the study and would have been premature. Trends are important to watch in order to decide if a particular patient compared to another patient would or would not benefit from a medicinal or preventative product. It is more individualized care. Additionally, trends can provide clues and direction to researchers.


The study authors were open and honest about the limitations of the study.

First, they could not determine whether all of the follow-up visits were due to the moxidectin injection.

The data they had to work with were based on actual clinical records. For example, some veterinarians and staff wanted to ensure they did not miss an important item during exams. According to the authors, some records had “vaccine reaction” marked on each and every visit to identify pets with a known history of vaccine reactions.

On the flip side, the authors would not have captured if a reaction was diagnosed, but had not been recorded in the proper field.

Bear in mind, moxidectin injection is not a vaccine and none of the dogs included had a vaccination during the initial visit. However, many vaccines are delivered by injection so this might have been the category chosen by the staff for moxidectin. The study authors decided to leave these notations in their final report.

Breed categories were based on pet caregiver reporting and not confirmed with breed registry papers.

Identified higher-risk breeds may not include all higher-risk breeds, because the analysis focused on more popular breeds that received the injection.

This study was highly dependent on pet caregivers to assess and determine if a follow-up visit is necessary. So, milder reactions may not have sparked a follow-up visit.

Finally, a pet companion parent may have taken a dog with a severe reaction to an emergency veterinary hospital instead of the clinic.


Estimate of adverse reactions: 14.3/10,000 doses administered.

1,999 events were identified, which equated to 1,875 dogs that had at least 1 visit with an acute adverse event within three days of the moxidectin injection out of 1,399,289 doses administered.

Diagnoses in descending order: nonspecific allergic reaction, mild vaccine reaction, acute allergic reaction, moderate vaccine reaction, and urticaria.

More severe events had lower occurrence: severe vaccine reaction (2.7%; 53), cardiac arrest (2; 0.1%), death while under treatment (2; 0.1%), and dead on arrival (1; 0.05%).

Incidence of acute adverse occurrence was highest in dogs less than 1.5 years of age and second highest in dogs between 1.5 and 2.5 years.

High risk breeds identified: Pit Bulls, American Staffordshire Terriers, French Bulldogs, Rhodesian Ridgebacks, American Bulldogs, Boxers, and Boston Terriers.

Assessment: Younger dogs and 7 breeds (relative to mixed-breed dogs) have statistically significant greater odds of an event within three days after moxidectin injection.


This study paper’s format listed the results before the limitations. We flipped them purposefully here because we did not want our readers to draw conclusions prior to knowing the limitations.

Due to the large dataset, we believe the results are valid. They provide a guidance of caution regarding the moxidectin injection in terms of age and breed.

We want to remind you that the scope did not include or comment on long-term outcomes. It was based solely on an acute adverse event within three days of product administration.

Additionally, please do not overlook the degree of reaction when reviewing the results. For instance, a mild reaction is swelling or fever. If you perpetually forget to give a monthly dose of heartworm preventative, it may be worth the risk of a mild reaction to the injectable preventative rather than the risk of heartworm disease.

Ultimately, the decision to have your companion dog receive this 6- or 12-month moxidectin injection should follow a discussion with your primary veterinarian.


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Dodds, W. Jean. “Canine Heartworm Disease.” Pet Health Resource, Tumblr, 24 Jan. 2016,

Dodds, W. Jean. “Flea and Tick Medications: Adverse Event Findings Released by Project Jake.” Hemopet, 10 Aug. 2020,

Dodds, W. Jean. “Heartworm: A Real and Present Danger.” Pet Health Resource, Tumblr, 3 May 2015,

Dodds, W. Jean. “MDR1 Gene Mutation in Dogs and Cats.” Pet Health Resource, Tumblr, 26 Mar. 2017,

Kryda, Kristina et al. “Preventive efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of Heartgard® Plus or Interceptor® Plus against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs.” Parasites & vectors vol. 13,1 339. 14 Jul. 2020, doi:10.1186/s13071-020-04178-z,

McTier, Tom L et al. “Comparative preventive efficacy of ProHeart® 12, Heartgard® Plus and Interceptor® Plus against a macrocyclic lactone-resistant strain (JYD-34) of heartworm (Dirofilaria immitis) in dogs.” Parasites & vectors vol. 14,1 226. 26 Apr. 2021, doi:10.1186/s13071-021-04708-3,

Myers, Jamie A E et al. “Preventive efficacy of six monthly oral doses of Simparica Trio®, Heartgard® Plus, and Interceptor® Plus against a macrocyclic lactone-resistant strain (ZoeLA) of heartworm (Dirofilaria immitis) in dogs.” Parasites & vectors vol. 15,1 81. 11 Mar. 2022, doi:10.1186/s13071-022-05180-3,

Saito, Emi K et al. “Younger dogs of specific breeds are more likely to experience a rare adverse event after administration of extended-release injectable moxidectin heartworm preventive.” Journal of the American Veterinary Medical Association, 1-7. 28 Jun. 2023, doi:10.2460/javma.23.04.0217,

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