Photo courtesy of Dr. Holt Pittman

Federal regulators lifted restrictions on ProHeart 6 following four-plus years of safety studies.

Federal restrictions on ProHeart 6 have been eased following more than four years of safety reviews by the U.S. Food and Drug Administration (FDA).

ProHeart 6, an injectible heartworm preventative that contains the active ingredient moxidectin, can be prescribed to any healthy dog older than six months, reflecting the end of a restriction that barred its use in dogs older than age 7. Veterinarians also are no longer required to obtain written consent from owners to use it, and they can direct veterinary technicians and assistants — provided they complete a 20-minute online certification course — to administer it to patients.

The regulatory changes, announced in late August by manufacturer Zoetis, Inc., reflect opinion by the FDA's Center for Veterinary Medicine that ProHeart 6 isn't as dangerous as once believed, largely due to modifications in how the drug is manufactured.

Fewer regulatory restrictions make it easier for practitioners such as Dr. Holt Pittman to use ProHeart 6 at his practice in Helena, Ark., where he says heartworm disease is rampant. "We're in the Mississippi Delta region; every dog is potentially heartworm positive here," Pittman said. "My opinion is that the moxidectin is effective, partly because giving a shot every six months helps with compliance."

ProHeart 6 is designed to prevent heartworm infestation for up to six consecutive months via twice-annual injections. Most other heartworm preventatives come in oral or topical forms that owners administer to their dogs on a monthly basis. ProHeart 6 does not offer protection against other common intestinal parasites like whipworm, roundworm or hookworm, although it can be used as a treatment for hookworms present at the time of administration.

Pittman says he used ProHeart 6 soon after its 2001 launch and continued doing so until it was removed from the U.S. market in September 2004, following reports that thousands of dogs experienced adverse reactions linked to the parasiticide, included death.

"We've never seen any reaction to the product," Pittman said.

But plenty of other veterinarians and pet owners did, prompting the FDA and then-manufacturer Fort Dodge Animal Health to begin evaluating the reported adverse events and conduct additional safety studies on ProHeart 6. (Ownership of ProHeart 6 has changed hands since its 2001 introduction by Fort Dodge Animal Health, a division of Wyeth. Pfizer purchased Wyeth in 2009, making ProHeart 6 a product of Pfizer Animal Health. Last year, Pfizer Animal Health spun off from Pfizer to become an independent company and adopted the name Zoetis, Inc. ProHeart 6 now is part of Zoetis' product portfolio.)

According to the FDA, the studies suggested that residual solvents used in the manufacture of ProHeart 6 could have caused the reactions, prompting Fort Dodge to alter the way it produced the pet parasiticide, which still was being sold overseas. "In the years following this change, there has been a decline in the adverse event reporting in international markets," FDA officials stated when ProHeart 6 was reintroduced to the U.S. market in 2008.
 
The return of ProHeart 6 came with a Risk Minimization Action Plan, or RiskMAP. As part of the FDA's RiskMAP program, Fort Dodge required veterinarians to register with the company and participate in intensive training in order to purchase ProHeart 6. The RiskMAP restricted treatment to healthy dogs aged between 6 months to 7 years. It also required veterinarians to provide owners with handouts on ProHeart 6 in addition to obtaining their written consent.

Since its reintroduction, adverse events are rare and often not serious, report Zoetis officials. ProHeart 6 has demonstrated "predictable safety and efficacy," officials said, prompting the company to modify its RiskMAP to ease the age restrictions and consent requirement.

“Although significant restrictions have been lifted, Zoetis remains committed to education on the proper use of ProHeart 6 and will continue to uphold the guidelines set forth by the FDA to help assure that veterinarians and, through them, pet owners, are aware of the benefits and risks of this product," said Dr. J. Michael McFarland, Zoetis' group director of Companion Animal Veterinary Operations in a recent online letter.

Federal regulators say they support the change.

”FDA reviewed Zoetis’ proposed changes to the voluntary RiskMAP and worked with the company on its implementation plan and supporting materials. FDA also considered the information collected by Zoetis over the last four years and the expert opinions presented at the last public meeting before accepting the modifications,” according to an emailed comment provided by the agency.