Visiting Vet: The saga of heartworm meds

The news has mostly gotten better, very quickly.

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Collies are among the breeds that may have an unusual genetic mutation. —Ramon Fabra

In 1977, the U.S. Food and Drug Administration approved the first canine heartworm preventive medication. I was just starting veterinary school. The drug was diethylcarbamazine, known simply as DEC, and it had to be given daily. By the time I graduated in 1981, it was standard practice to advise clients to give a DEC tablet to their dogs every day. In warmer climates, DEC was given year-round. Up north, we usually advised April to Christmas. Heartworm is a parasite carried by mosquitoes, but DEC works on only a very specific molting stage of the worm larvae, so there was a lag time between the end of mosquito season and the end of “give DEC daily” season. This resulted in a lot of veterinarians tearing out their hair, because owners kept stopping the preventive as soon as mosquito season ended. But eventually, most people understood. April to Christmas. Every. Single. Day.

Which led to another problem. I can’t tell you how many times I got panicked phone calls early in the morning from people who had inadvertently taken their dog’s DEC, thinking it was their own multivitamin. The calls were so common I would warn folks. “Please don’t keep these on your kitchen counter next to your One A Day vitamins.” Yet people continued to do so. My official answer to these 6 am calls was always, “I can’t give you human medical advice.” My addendum was, “I get these calls pretty often, and no one has ended up in the ER yet.”

In the mid-1980s, a large, flavored chewable treat style of DEC called Filaribits came on the market. This made life a bit easier for many owners who chose to spend the extra money for the convenience. I’m sure sales of peanut butter and cream cheese went down at Cronig’s, too, since owners no longer had to hide the daily DEC dose in a treat. Although some owners opted to stick with the more economical plain tablets, the number of those “I took my dog’s heartworm pill” emergency phone calls dropped significantly.

One of the down sides of DEC is that, if given to a dog who actually had a heartworm infection, the results could be deadly. Back in those days, we ran heartworm clinics every spring, trying to make sure all our patients tested negative before beginning the preventive. Then came 1987, and the introduction of Heartgard, the first once-a-month heartworm pill. Life got even easier, for both veterinarians and dog owners. Well, there was the issue that for some humans, remembering to do something once a month apparently is harder than doing something every day, but overall, compliance was good, and we all quickly made the transition to this new routine.

Then in 2001, scientists discovered a weird genetic mutation in collies. The gene involved is called the multi-drug-resistance gene, or MDR-1. This gene is essential for the production of a substance called p-glycoprotein, which protects dogs from major side effects of certain drugs. A defective gene makes affected individuals more sensitive to these negative side effects. Now, remember your high school genetics. Genes come in pairs of alleles — one from each parent. A dog can have two normal MDR1 alleles (normal/normal). That dog is good to go. Or a dog can have the mutation on just one allele (normal/mutant), or on both alleles (mutant/mutant). Pups testing positive for MDR1 mutation, whether homozygous or heterozygous (high school genetics again!), are at risk for adverse reactions to several commonly used veterinary medications, including ivermectin, the main component of many monthly heartworm medications. Ivermectin toxicity usually manifests with weakness, lethargy, disorientation, and incoordination … and it can be fatal.

When this information first started coming out in the literature, we were focused specifically on collies and other herding breeds. In fact, we had a saying in those days: “White feet, don’t treat.” That turned out to be a bit too simplistic. Not every dog with the MDR1 mutation has white feet, and vice versa. The most commonly affected breeds currently identified include collie, longhaired whippet, Australian shepherd, and miniature Australian shepherd — with 50 to 70 percent of individuals in those groups carrying the mutation. It is now thought that all MDR1 mutant dogs are descended from a single dog who lived in Great Britain sometime before the mid-1800s — i.e., before people began identifying and registering breeds by genetic bloodlines. Other breeds affected (albeit at much lower rates) include a few I’ve never heard of, such as McNab shepherds and silken windhounds, and some I see frequently, such as Shelties, German shepherds, border collies, and Old English sheepdogs. But even mixed-breed dogs have occasionally been found to have the mutation.

So how do you know if your pup Colin, the collie, is a carrier? Simple. Test him. It’s easy. You can do it yourself. Researchers at Washington State University developed the test. Order a cheek swab from them, follow the directions, submit the test. All the necessary information is at prime.vetmed.wsu.edu. Or ask your veterinarian to submit a blood sample. It is good to have this information, especially if you have a high-risk breed.

Please don’t panic if Colin is affected. Heartgard and other ivermectin-containing preventives are perfectly safe for him at the labeled dosages. Some veterinarians may use different heartworm medications for these pups, but it’s really not necessary. In fact, we now know that several of the other heartworm preventives, though safe as labeled, can also be problematic for MDR1-mutant dogs at higher doses. Here’s what’s essential. We can’t give Colin ivermectin at the high doses used to treat demodectic mange. Don’t use the over-the-counter antidiarrheal medication loperamide (brand name: Imodium). Your veterinarian has a list of prescription drugs to avoid, including certain sedatives, chemotherapeutic agents, and a few other medications. But instead of guessing who’s at risk and who isn’t, think about doing that cheek swab on Colin at home. Because knowledge is power.