July 2, 2019
The U.S. Food and Drug Administration’s Center for Veterinary Medicine announced today the approval of ProHeart 12 (moxidectin) extended-release injectable suspension for dogs 12 months of age and older for the prevention of heartworm disease caused by Dirofilaria immitis for 12 months. ProHeart 12 is also approved for the treatment of existing larval and adult hookworm infections.
Heartworm disease is a serious disease that results in severe lung disease, heart failure, other organ damage, and death in pets, mainly dogs, cats, and ferrets. It is caused by a parasitic roundworm called Dirofilaria immitis. The worms are spread through the bite of a mosquito. While living inside a dog, the worms mature into adults, mate, and produce offspring. The worms are called “heartworms” because the adults live in the heart, lungs, and associated blood vessels of an infected animal. In the United States, heartworm disease has historically been most common along the Atlantic and Gulf coasts from the Gulf of Mexico to New Jersey and along the Mississippi River and its major tributaries, but it has been reported in dogs in all 50 states.
Moxidectin is a macrocyclic lactone antiparasitic compound already approved in an extended release formulation as ProHeart 6, with a six-month duration of action for heartworm disease prevention. The ProHeart 12 formulation is the same as the previously approved product but contains three times the concentration of moxidectin, resulting in a 12-month duration of action.
ProHeart 6 was approved in 2001, then voluntarily removed from the market in 2004 after reports of adverse events, including death, anaphylaxis, seizures, elevated liver enzymes, and immune-related blood problems. The FDA worked with the drug maker (at the time, Fort Dodge Animal Health), to develop a voluntary Risk Minimization Action Plan (RiskMAP) for ProHeart 6 that set several conditions in place, including restricted distribution of the drug to veterinarians who had completed specific training and certification, informed consent on the part of dog owners prior to treatment, revised product labeling with additional safety and risk information, and the establishment of certain criteria that dogs should meet to determine whether treatment with the drug was appropriate. The RiskMAP also encouraged veterinarians and pet owners to report adverse events associated with the product to the FDA. The drug sponsor also worked to eliminate residual solvents resulting from the manufacture of the product and that may have contributed to the reported adverse events. When ProHeart 6 returned to the market with the implementation of the RiskMAP, reports involving death, including reports of death associated with anaphylactic reactions, decreased. Since that time, the conditions imposed by the ProHeart 6 RiskMAP have been revised based on the FDA’s continued close monitoring of reports of adverse events. The drug maker has added ProHeart 12 to the existing RiskMAP for ProHeart 6 to ensure the safe use of both products.
The safety of ProHeart 12 was evaluated in five laboratory studies and a field study in client-owned dogs. The laboratory studies included a margin of safety study, a study to evaluate safety in dogs infected with heartworms, a study to evaluate safety in ivermectin-sensitive collies, and reproductive safety studies in both female and male dogs. In total, safety was evaluated in 404 animals, including in 297 client-owned dogs.
Adverse events observed in the U.S. field study for ProHeart 12 included vomiting, diarrhea, decreased appetite (anorexia) and seizures and occurred in a similar rate to those dogs that were in the control group. The cases of anorexia observed in the study were generally mild and short in duration, and all cases resolved by the conclusion of the study. One dog had a seizure 19 days after initial treatment with ProHeart 12. The seizure was severe, and the dog required medical treatment. The other seizures reported were mild, single incidents that did not appear to occur in association with ProHeart 12 treatment.
In addition, two dogs treated with ProHeart 12 experienced mild to moderate hypersensitivity-related drug reactions within the first 24 hours of the initial treatment. Both dogs experienced full recoveries, and neither dog had a reaction when they received a second dose of ProHeart 12 a year later. Some dogs also experienced injection site inflammation.
To supplement the pre-approval safety evaluation for ProHeart 12, the FDA reviewed voluntarily-reported adverse event data from foreign markets, including Australia, where ProHeart 12 has been approved since 2000. This information, in conjunction with the U.S. adverse event data for ProHeart 6, supported a determination of safety for ProHeart 12.
The effectiveness of ProHeart 12 was demonstrated in two laboratory dose confirmation studies and a field study of 297 client-owned dogs that were administered the product. All studies demonstrated the product to be 100 percent effective in the prevention of heartworm disease for one year.
ProHeart 12 is available in two sizes – a 10 mL size and 50 mL size – and is manufactured by Zoetis Inc., based in Kalamazoo, Michigan.
For more information:
- Freedom of Information Summary – ProHeart 12
- Keep the Worms Out of Your Pet’s Heart! The Facts about Heartworm Disease
Issued by FDA Center for Veterinary Medicine.
For questions, Contact CVM.