ProHeart 6 and ProHeart 12 are the only FDA-approved injectable heartworm preventives for dogs. Both contain moxidectin in a sustained-release microsphere formulation, administered by a veterinarian — but they differ in concentration, duration of protection, minimum patient age, and the compliance convenience they offer. ProHeart 12 provides 12 months of heartworm prevention from a single injection; ProHeart 6 provides 6 months.

This article compares the two products head-to-head, explains the safety history that led to the FDA's Risk Minimization Action Plan (RiskMAP), and helps veterinary professionals and dog owners decide which product fits which patient.

Quick answer

ProHeart 6 and ProHeart 12 contain the same active ingredient (moxidectin) in the same type of sustained-release formulation. ProHeart 12 is three times more concentrated, providing 12 months of protection per injection versus ProHeart 6's 6 months. ProHeart 6 can be used in dogs 6 months of age and older; ProHeart 12 requires dogs to be at least 12 months old. Both are available only through a restricted distribution program requiring veterinarian certification. Both also treat existing larval and adult hookworm infections at the time of injection.

Neither product protects against fleas, ticks, roundworms, whipworms, or tapeworms. A separate flea/tick preventive and broad-spectrum intestinal worm coverage are still needed.

What ProHeart products are and how they work

Moxidectin is a macrocyclic lactone antiparasitic that kills heartworm larvae (Dirofilaria immitis L3 and L4 stages) before they can develop into adult worms. When injected subcutaneously, the moxidectin is encapsulated in biodegradable microspheres that slowly release the drug over months, providing continuous heartworm prevention without the need for monthly dosing.

Both products also treat existing larval and adult hookworm (Ancylostoma caninum and Uncinaria stenocephala) infections at the time of injection.

ProHeart 6 vs ProHeart 12: key differences

Dosing

ProHeart dosing is calculated by the dog's body weight. The formula is: weight (lbs) / 2.2 = kg; kg x 0.05 mL = dose in mL. Because ProHeart 12 is three times more concentrated, the injection volume is smaller than ProHeart 6 for the same dog.

Dogs older than 6 months but younger than 12 months should receive ProHeart 6, not ProHeart 12.

The safety history and the RiskMAP

ProHeart 6 was originally approved by the FDA in 2001. In 2004, after reports of adverse events including death, anaphylaxis, seizures, elevated liver enzymes, and immune-mediated blood disorders, the manufacturer (then Fort Dodge Animal Health) voluntarily withdrew the product from the market.

The FDA worked with the manufacturer to develop a Risk Minimization Action Plan (RiskMAP). Key elements included:

• Restricted distribution to veterinarians who completed a web-based training and certification program
• Informed consent from pet owners before each injection
• Revised product labeling with additional safety warnings
• Pre-treatment requirements: dogs must be healthy, not underweight, and tested heartworm-negative
• Enhanced pharmacovigilance and adverse event reporting

ProHeart 6 returned to the market under the RiskMAP, now manufactured by Zoetis (the animal health company spun off from Pfizer). The FDA conducted a 4.5-year safety review that showed a significant decrease in death reports relative to estimated exposure. Based on this data, several RiskMAP restrictions were lifted — including expanded age eligibility (up to 7 years) and allowance for trained veterinary technicians to administer the injection.

When ProHeart 12 was approved by the FDA in 2019, it was added to the existing ProHeart 6 RiskMAP. The FDA noted that both products contain the same moxidectin microspheres and have similar safety profiles.

What the RiskMAP means in practice

Before your dog can receive either ProHeart product, your veterinarian must:

1. Be certified through the Zoetis RiskMAP training program
2. Confirm your dog is healthy (not sick, debilitated, or underweight)
3. Perform a heartworm test and confirm a negative result
4. Discuss the benefits and risks with you and obtain your informed consent
5. Monitor your dog at the clinic for a period after the injection

Adverse reactions

Both products share a similar adverse event profile because they contain the same active ingredient in the same formulation at different concentrations.

Common side effects (from clinical trials)

• Vomiting
• Lethargy or depression
• Diarrhea (with or without blood)
• Decreased appetite
• Injection-site swelling or itching

Serious adverse reactions (from the label and post-marketing reports)

The ProHeart 12 label lists the following categories of adverse events based on experience with ProHeart 6:

• Allergic/immune: Anaphylaxis, anaphylactoid reactions, facial swelling, urticaria, collapse, cardiovascular shock, immune-mediated hemolytic anemia, immune-mediated thrombocytopenia
• Gastrointestinal: Vomiting (with or without blood), diarrhea, hypersalivation
• Neurologic: Seizures, ataxia, trembling, hind limb paresis
• General: Lethargy, anorexia, fever, weight loss, weakness
• Hepatic: Elevated liver enzymes, hepatopathy
• Dermatologic: Injection-site pruritus, swelling, erythema multiforme
• In some cases, death

These reactions are rare but can occur without warning. The label notes that anaphylactic reactions can result in death and should be treated immediately with the same emergency measures used for hypersensitivity reactions to vaccines and other injectable products.

Who should not receive ProHeart

Per the label, do not administer ProHeart to dogs that are:

• Sick, debilitated, or underweight
• Experiencing a history of unexplained weight loss
• Previously found to be hypersensitive to moxidectin
• Younger than 6 months (ProHeart 6) or 12 months (ProHeart 12)

Use with caution in dogs that are:

• Receiving vaccinations at the same visit (allergic reactions have been reported when ProHeart and vaccines were administered together)
• Heartworm-positive (the product prevents new infections but is not effective against adult heartworms; reactions can occur as larvae die)
• Pregnant, nursing, or used for breeding
• Have pre-existing allergic disease
• Have kidney or liver disease

Which dogs benefit most from injectable prevention

ProHeart 12 may be the best fit when

• The owner has difficulty remembering monthly doses — a single annual injection eliminates compliance gaps
• The dog is at high risk for heartworm disease in an endemic area and missed doses are a real concern
• The owner travels frequently and cannot reliably administer monthly chews
• The dog tolerates injections well and has no history of allergic reactions to injectable medications

ProHeart 6 may be the best fit when

• The dog is between 6 and 12 months old (too young for ProHeart 12)
• The owner prefers twice-yearly clinic visits for wellness checks and heartworm testing
• The veterinarian wants to assess tolerance with a lower-concentration formulation before switching to ProHeart 12

Monthly preventives may be better when

• The dog also needs flea and tick coverage (products like Simparica Trio or NexGard Plus cover heartworm, fleas, ticks, and intestinal worms in one chew)
• The dog has had a previous allergic or adverse reaction to an injectable medication
• The owner prefers to avoid injections and is reliable with monthly dosing
• The dog has multiple parasiticide needs that a single monthly chew can address

ProHeart vs monthly chews: compliance and coverage

The primary advantage of injectable heartworm prevention is compliance. The American Heartworm Society (AHS) recommends year-round heartworm prevention, but compliance data show significant gaps. A 2021 pharmacoeconomic study in Frontiers in Veterinary Science found that only about 56% of dogs prescribed monthly prevention received enough doses to cover six months of the year. Research presented at WSAVA estimated that fewer than one-third of dogs under veterinary care receive adequate year-round heartworm prophylaxis. Each missed dose creates a gap in protection, especially during mosquito season.

A 2021 study by McTier et al. published in Parasites & Vectors found that ProHeart 12 was 98–100% effective in preventing development of the JYD-34 heartworm strain — a strain known to be resistant to macrocyclic lactone preventives. This efficacy is comparable to monthly preventives when given on schedule.

However, ProHeart products cover only heartworm and hookworm. Most monthly combination products also cover fleas, ticks, roundworms, whipworms, and sometimes tapeworms. Dogs on ProHeart will still need a separate product for those parasites.

Questions to ask your veterinarian

• Is my dog healthy enough for an injectable heartworm preventive?
• Does my dog's heartworm test need to be repeated before starting ProHeart?
• Will my dog need separate flea and tick prevention?
• Can ProHeart be given at the same visit as vaccines?
• What should I watch for after the injection, and when should I call the clinic?
• How does the cost of annual ProHeart 12 compare to 12 months of a chewable combination product?

Sources

• FDA CVM Update: FDA Approves ProHeart 12 (moxidectin) for Prevention of Heartworm Disease in Dogs — https://www.fda.gov/animal-veterinary/cvm-updates/fda-approves-proheart-12-moxidectin-prevention-heartworm-disease-dogs
• ProHeart 12 label (DailyMed) — https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=e856da36-f717-4645-8841-27460cf87d91
• FDA ProHeart 6 and ProHeart 12 RiskMAP document — https://www.fda.gov/media/87188/download
• Zoetis ProHeart dosing chart — https://www.zoetisus.com/content/_assets/docs/Petcare/proheart/ProHeart-12-ProHeart-6-Dosing-Administration-Charts.pdf
• Zoetis Petcare: ProHeart 12 for pet owners — https://www.zoetispetcare.com/products/proheart
• VCA Animal Hospitals: Moxidectin Injectable (ProHeart 6, ProHeart 12) — https://vcahospitals.com/know-your-pet/moxidectin-injectable
• dvm360: Risk requirements eased for ProHeart 6 — https://www.dvm360.com/view/risk-requirements-eased-proheart-6-injectable-heartworm-control
• McTier et al. (2021), "Comparative preventive efficacy of ProHeart 12, Heartgard Plus, andInterceptor Plus against the ML-resistant JYD-34 heartworm strain," Parasites & Vectors — https://pmc.ncbi.nlm.nih.gov/articles/PMC8074443/
• Cornell University College of Veterinary Medicine: Heartworm Disease — https://www.vet.cornell.edu/departments-centers-and-institutes/riney-canine-health-center/canine-health-information/heartworm-disease
• American Heartworm Society: Preventives — https://www.heartwormsociety.org/preventives