Heartgard Plus is one of the safest medications used in veterinary medicine when given according to label instructions. In clinical trials, only 1.1% of doses caused any digestive side effects like vomiting or diarrhea within 24 hours. The American Heartworm Society recommends year-round heartworm prevention for all dogs, and Heartgard has been used safely in millions of dogs for decades.
What Heartgard Does
Heartgard Plus contains two active ingredients that target different parasites. The first, ivermectin, kills heartworm larvae that mosquitoes deposit under your dog’s skin before those larvae can migrate to the heart and lungs. The second, pyrantel, treats and controls two common intestinal parasites: roundworms and hookworms. Together, the monthly chewable prevents heartworm disease while keeping the gut clear of worms that can cause weight loss, diarrhea, and anemia.
Side Effects in Most Dogs
The most commonly reported side effects are vomiting, diarrhea, lethargy, and loss of appetite, typically appearing within a day of dosing. These reactions are infrequent. In controlled clinical trials, digestive upset occurred after just 1.1% of administered doses. Most dogs chew the beef-flavored tablet and show no reaction at all.
Post-approval reporting to the FDA paints a similar picture. The adverse events reported most often, in order of frequency, are vomiting, diarrhea, lethargy, loss of appetite, seizures, loss of coordination, muscle tremors, excessive drooling, and itching. That list sounds alarming, but it represents a tiny fraction of the tens of millions of doses given each year, and not every reported event is necessarily caused by the medication. In rare cases, choking or intestinal blockage has been reported after administration, likely related to the chewable tablet itself rather than the drug.
The MDR1 Gene and Sensitive Breeds
Certain breeds carry a genetic mutation called MDR1 that affects how their bodies process drugs like ivermectin. Dogs with this mutation can’t pump the drug out of their brain cells efficiently, which at higher doses can lead to serious neurological problems. About 70% of Collies in the United States carry the mutation. Other breeds with significant rates include Australian Shepherds (50%), Long-haired Whippets (50%), McNabs (30%), Silken Windhounds (30%), Chinooks (25%), Shetland Sheepdogs (15%), English Shepherds (15%), and German Shepherds (10%). Mixed-breed dogs, particularly those with herding breed ancestry, carry it at roughly a 5 to 10% rate.
Here’s the key distinction: the heartworm prevention dose of ivermectin in Heartgard is extremely low, just 6 micrograms per kilogram of body weight. Toxicity signs in sensitive Collies don’t appear until doses reach about 100 micrograms per kilogram, which is more than 16 times the Heartgard dose. At that threshold, only 30 to 40% of Collies show mild signs. The manufacturer states that Heartgard Plus is safe for all breeds, including Collies. If you have a breed on this list and want extra peace of mind, a simple cheek-swab DNA test from your vet can confirm whether your dog carries the MDR1 mutation.
What Ivermectin Toxicity Looks Like
Although toxicity from a standard Heartgard dose is extraordinarily unlikely, it’s worth knowing the signs in case a dog accidentally eats multiple tablets or gets into a livestock-grade ivermectin product. Symptoms include unsteady walking, disorientation, tremors, excessive drooling, dilated pupils, heightened sensitivity to touch, blindness, depression, and in severe cases, coma. These signs typically appear within hours of a large overdose. If your dog ever ingests more than one dose or gets into another ivermectin product, contact your vet or an animal poison control hotline immediately.
Puppies, Pregnant Dogs, and Breeding Dogs
Heartgard Plus is approved for puppies as young as 6 weeks of age, with no minimum weight requirement (the lowest dosing range covers dogs up to 25 pounds). The American Heartworm Society recommends starting puppies on prevention as early as possible and no later than 8 weeks. Puppies started after 8 weeks should be tested for heartworm 6 months after their first dose and then annually.
The medication has also demonstrated a wide margin of safety in pregnant dogs, lactating dogs, breeding females, and stud dogs. There are no restrictions on using Heartgard throughout pregnancy or the nursing period.
Testing Before Starting Prevention
For dogs older than 7 months, or any dog without documented testing in the past 12 months, a heartworm test should be performed before starting Heartgard. This involves checking for both heartworm proteins (antigen test) and immature heartworms circulating in the blood (microfilaria test). Giving a preventive to a dog that already has an adult heartworm infection won’t treat the disease and can, in some situations, cause complications.
The American Heartworm Society recommends annual screening for all dogs over 7 months old. If you’ve missed doses, switched products, or had any gaps in prevention, your dog should be tested before restarting and again 6 months later. A positive result doesn’t mean prevention failed necessarily; it may indicate an infection that predated the preventive or developed during a coverage gap.
Why Year-Round Dosing Matters
Skipping winter months is one of the most common mistakes dog owners make with heartworm prevention. Mosquito seasons are unpredictable, and a single missed dose opens a window for larvae to survive and mature. Year-round dosing also eliminates the risk of forgetting to restart in spring, which is when many gaps occur. Both the American Heartworm Society and the FDA recommend 12-month, uninterrupted prevention. The continuous schedule also keeps roundworm and hookworm infections in check, parasites that don’t follow a seasonal pattern at all.