At Dr. Marie Leslie’s veterinary practice in Florida, a state where canine heartworm is rampant, fewer than half the patients have a prescription for heartworm-control medication. Logic says droves of sick dogs should be showing up on Leslie’s doorstep. But they’re not. 

Are these dogs immune? Has something changed in Florida’s environment to blunt the proliferation of heartworms? Not likely.   

Leslie believes the answer to this apparent paradox lies on the shelves of her local feed store. Like most feed stores, it sells antiparasitic drugs for livestock over the counter (OTC). Clients have admitted to Leslie that they use products such as horse deworming paste as a cheap method of preventing heartworm infection in their dogs.
   
Although Leslie advises owners that livestock products aren’t approved for dogs and improper dosing may be toxic or ineffective, most owners elect to continue their use.

Horse deworming paste contains ivermectin, the same active ingredient found in many canine heartworm preventives. Ivermectin kills helminths, worm-like parasites that come in a variety of forms and infest a variety of species. Canine heartworms are one example of these parasites; others are roundworms and hookworms.   

Because it's the same active ingredient, some pet owners believe they can simply scale down the horse product for dogs. Here's the problem: Pound for pound, dogs require a much smaller dose than horses of ivermectin. And different products contain varying concentrations of the ingredient, which is why different products are labeled and regulated differently for different species.

While products to control heartworms in dogs and cats require a prescription in the United States, all ivermectin products for food animals are labeled for OTC sale. The position of the U.S. Food and Drug Administration (FDA) is that a veterinarian’s guidance is needed to control heartworms due to the parasite’s complicated life cycle, whereas controlling helminths in livestock — principally nematodes such as roundworms — is considered less complex.   

The divergent rules have existed for decades. Companion animal practitioners have long been concerned about the toxicities resulting from inaccurate dosing in dogs and recently have been begun wondering about other consequences. Their worries are prompted by recent news that heartworm drug resistance is taking hold.

Information presented at a meeting of the American Association of Veterinary Parasitologists last July confirmed what many had feared: Strains of canine heartworm exist that are resistant to an entire class of drugs known as macrocyclic lactones — basically all canine heartworm preventive medications sold commercially, including ivermectin.  

The finding leads experts to caution veterinarians about certain uses of the drugs. But veterinarians such as Leslie doubt whether clinicians can do much to stop resistance development in the face of inappropriate use by pet owners of livestock drugs.   

“We can try to educate these clients all we want, but we will always lose out to easy access and cheap price,” she commented to colleagues on a message board of the Veterinary Information Network (VIN), an online community for the profession. “Let’s quit ignoring the ‘elephant in the room’ and work to stop this problem at the root: easy access to and mis-administration of what should be a prescription medicine. Until that happens, we as veterinarians are no more effective than gnats trying to stop the resistance trend.”   

The situation begs the question, how did ivermectin for livestock versus dogs and cats come to be treated differently?   

The FDA says the classification of a drug as OTC or prescription has to do with how easily a layperson can follow directions for proper use.   

In an explanation provided by email, the FDA said it “must assess whether adequate directions for a layperson to safely and effectively use the drug can be written. If such directions can be written for a particular product or a particular intended use, then it’s an OTC product. But if the supervision of a veterinarian is needed to ensure the safe and effective use of the drug, it will only be made available by prescription.”   

In the case of ivermectin specifically, the FDA said: “Ivermectin, like all macrocyclic lactone drugs indicated for heartworm prevention for dogs, are prescription only because a veterinarian’s expertise is necessary to ensure the safe and effective use of the drug. A veterinarian’s understanding of the heartworm life cycle and interpretation of the heartworm screening test ensures that heartworm preventatives are used appropriately to achieve the intended effect and minimize adverse effects.”   

The agency’s response continued: “Ivermectin drug products have been labeled OTC in food animals because it is possible to provide directions of use that can be followed by the layperson. Diagnosis of parasitism is not required prior to treatment due to the epidemiology of nematode parasites in food animals. Food animals are always exposed to parasite eggs and larvae, and treatment is necessary periodically and should be used as part of an integrated parasite management program.”

Although livestock ivermectin drugs are easily accessible to consumers OTC, any use in animals or for conditions not explicitly stated on the drug label actually requires a veterinarian’s authorization. In other words, it is illegal for pet owners to give their dogs livestock ivermectin without a prescription.   

The rules for what’s known as extra-label use of animal drugs is spelled out in the Animal Medical Drug Use Clarification Act (AMDUCA). As explained in an FDA summary of the law, extra-label use of animal drugs is legal only under the order of a licensed veterinarian within the context of a valid veterinarian-client-patient relationship.   

The typical pet owner is unlikely to be aware of the provisions of AMDUCA, however, and legal consequences to a pet owner for using OTC animal drugs inappropriately seem equally unlikely.  

Asked whether there is any way for the government to monitor or control how OTC animal drugs are used once they reach the shelves of feed stores or pet stores, the FDA implied that its focus for proper drug use is in food animals. It did not address enforcement action involving companion animals.   

“FDA’s role is to evaluate drug products for safety and effectiveness, and to ensure that they are properly labeled. We also work with the Federal Trade Commission to monitor advertising, and we do outreach through both veterinary and animal-producer associations to promote proper use through education,” the agency stated. “… We strongly encourage that pet owners and animal producers work with their veterinarians to develop treatment plans. Should extra-label use of a product result in tissue residue violations in food animals, FDA may investigate the nature of the drug (mis)use and take appropriate action.”   

How often dog owners succumb to the lure of cheap and easily available antiparasitic drugs is impossible to know. Like Leslie, Dr. Fred Gingrich, a mixed-animal veterinarian in Ohio, believes that “inappropriate drug use is probably common with OTC products.”   

Gingrich said he has treated a couple of dogs that were overdosed on ivermectin. He suspects those patients are but a small fraction of the casualties in his region. “I probably haven’t seen that much because those types of people don’t bring their dogs to a veterinarian,” he speculated.   

A search of the Internet yields multiple references to the use of OTC livestock drugs as a cheaper alternative to prescription products for dogs.   

For example, the website Dime Store Budget, after giving a disclaimer that the writer is not a veterinarian and that “should you follow the steps below, you are doing so at your own risk and that of the risk to your pet,” goes on to give a detailed how-to.   

Yahoo! Answers, a popular website for questions and answers, features a discussion about the availability and limitations of feed-store drugs. Several responses to a questioner stress the importance of consulting a veterinarian to treat a heartworm infestation.   

Several sites address dosing. Because dogs are not small cattle, simply scaling down the amount of drug based on the dog’s size will not give the right dose.

A look at the various ivermectin products illustrates extreme differences in price and difficulties inherent in transferring products between species. Six doses of one name-brand heartworm-prevention product (containing ivermectin and pyrantel) for a 50-pound dog costs roughly 15 times the price of a tube of generic ivermectin paste dewormer dosed for a 1,280-pound horse. Figuring out how much of that tube to give to a dog is fraught with risk.  

For example, one type of equine paste contains 1.87 percent ivermectin in 6.08 grams of product. The ivermectin dose for dogs is measured in micrograms (millionths of a gram). Translating a percentage concentration into micrograms of ivermectin per tube and then determining and measuring out the volume of paste to give to a dog of a certain weight involves multiple calculations that could make most heads spin — and easily result in critical errors.

Moreover, little is known about the safe or effective use in dogs of products formulated for horses or cattle, according to Dr. Andrew Peregrine, a clinical parasitologist at the University of Guelph in Canada. That, he said, creates “a huge risk of overdosing or under-dosing.”

The risk is greater still for collies and other herding breeds. When ivermectin-based heartworm medications were introduced in the 1980s, most collies and related breeds were found to be exquisitely sensitive to the compound.

In today’s FDA-labeled heartworm preventives for dogs, the amount of ivermectin is well below the toxicity threshold for dogs with the genetic sensitivity. As a result, Peregrine said, in collies whose heartworm prevention regimen is overseen by a veterinarian, cases of ivermectin toxicity are rare.

But incidents still occur. “Most cases heard of nowadays are (a result of) people choosing to dilute the cattle product to use in dogs,” Peregrine says.

As risky as overdosing a drug can be to an individual pet, under-dosing also poses a significant, if more insidious, danger.

Peregrine explains: “When people are using drugs without the supervision of a veterinarian, the chances of using it at an inappropriate time of year or below the licensed dosage are higher. Under-dosing, we think, more quickly selects for resistance by allowing more parasites with genes for resistance to survive.”   

In other words, by not giving a sufficient dose of the drug, parasites that are somewhat resistant are able to live and reproduce, passing on the trait of resistance to new generations.

For that reason, Peregrine agrees with Leslie that OTC availability of heartworm medications is worrisome. “If we’re going to seriously address resistance, my own opinion is that you should ban OTC sales,” he says.   

The FDA appears receptive to the point but was noncommittal when asked whether it shares the concern that inappropriate use of OTC animal drugs could contribute to resistant microbes or parasites. The agency stated:

“FDA is concerned with the continued safety and efficacy of all approved animal drugs. FDA continually evaluates information concerning the products, and when issues or concerns are identified, takes appropriate action, which can also include education or outreach efforts.”   

Reclassifying an OTC animal drug to require a veterinarian’s authorization isn’t unheard of. The FDA earlier this year announced a plan to ask drug makers to revise labels on certain OTC livestock antibiotics so that they require veterinary oversight. Affected antibiotics are those important in human medicine; the change is driven by growing concern about microbial resistance. The pharmaceutical industry and producers, by and large, support the change. 
    
If OTC antiparasitic livestock drugs were to be reclassified as prescription medications, it would end a long-established tradition of enabling ranchers to treat their stock independent of veterinary involvement.  

There’s also an issue for some producers in remote locations of access to veterinarians. Gingrich, the Ohio practitioner who takes care of large and small animals alike, says: “The biggest disadvantage of restricting these drugs to Rx products is that it would require a veterinarian. In some areas of the country, there may not be a veterinarian, and there never will be a veterinarian available.”   

However, the rural landscape is shifting as agriculture consolidates, with livestock production handled by fewer and larger producers. In light of this shift, Gingrich says convenient access to drugs by producers is less pressing.   

“We have to ask ourselves in 2013, if someone is raising animals for food, should they be able to treat them with anything they want? I’d say no. For me, if you want to raise food, there are certain things you have to do to raise that food safely, humanely and appropriately.”   

For Gingrich, that means that “We need to speak for the animal as well as the consumer. If you speak for the animal and the consumer, there’s no reason to have full access to some of those products.”