Problems with Dog Medications and the MDR1 Gene

Learn if your dog is susceptible to certain medication problems with a simple genetic test.

By By Deb Eldredge, DVM | April 25, 2013

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Heartworm life cycle

When word got out in August 2011 that there was, and would be, a shortage of the only medication approved to treat adult heartworms in dogs, most conformation dog show fanciers merely shrugged. The American Heartworm Society came up with a protocol to manage dogs that might not be able to get treatment due to the drug shortage. (So far, veterinarians with infected canine patients have been able to contact Merial and obtain just enough of the regular heartworm drug held in reserve to treat those individual dogs.)

The heartworm drug shortage came about due to a problem with a United States supplier of one of the ingredients. The FDA is not comfortable with an overseas supplier of that ingredient, so while bottleneck was straightened out, access was limited. Still, very few purebred show dogs were affected by the heartworm drug shortage.

More crucial was the Novartis shortage of some heartworm preventive medications — namely Interceptor and Sentinel. This shortage was due to a problem at a United States manufacturing plant. It appears that some human medications from the plant may have been mixed with other human medications when packaged. There was no problem per se with the Interceptor or Sentinel heartworm medications, but this plant manufactured these drugs also.

Shutting the plant down to correct the problems with those human medications limited these heartworm medications for dogs until April 2013. On April 22, 2013, Novartis Animal Health announced that Sentinel (milbemycin oxime/lufenuron) Flavor Tabs was back on the market at nearly half the 2011 prices. Novartis also announced that it had discontinued the production of Interceptor (milbemycin oxime) Flavor Tabs for the US market.

 

Mutated MDR1 Gene and Medications

Dog Breeds affected by the
MDR1 mutation (frequency %)

Dog Breed

Approximate Frequency

Australian Shepherd

50%

Australian Shepherd, Mini

50%

Border Collie

< 5%

Collie

70%

English Shepherd

15%

German Shepherd Dog

10%

Herding Breed cross

10%

Long-haired Whippet

65%

McNab

30%

Mixed Breed

5%

Old English Sheepdog

5%

Shetland Sheepdog

15%

Silken Windhound

30%

The real challenge with heartworm prevention comes for the dogs who have a mutation of the MDR1 (multi drug resistance) gene. These dogs have problems metabolizing certain drugs safely, so they don’t limit drug absorption and distribution. Think of it as "leaky brain/blood barrier.”

Depending on the dose of the drug, these dogs can become ill or even die. Drugs that cause problems in these dogs include: acepromazine, butorphanol, doxorubicin, erythromycin, ivermectin, loperamide, milbemycin, moxidectin, rifampin, selamectin, vinblastine and vincristine. These drugs run the gamut from tranquilizers to antibiotics to chemotherapy drugs and, significantly, heartworm preventives.

The FDA-approved heartworm medications for dogs have levels of ivermectin, milbemycin, etc., that are safe for these pet dogs. Katrina Mealey, DVM, Ph.D., DACVIM, DACVCP of Washington State University, where the work on MDR1 and the testing for this mutation is done, stressed that point. She also emphasized that it is not safe to try and "guesstimate” a dose for your dog from one of the large-animal heartworm preparations, including the equine paste dewormers.

In a case local to me, a veterinarian’s top agility Border Collie licked up a few spots of the apple-flavored paste dewormer that her horse had dribbled. A few days later, Border Collie went blind. Even the veterinary ophthalmologist who evaluated her felt it was likely to be a permanent change.

Luckily for that dog, she did recover and is even running agility again. Other local dogs, including an Australian Shepherd who ate manure within 48 hours after the horses at her barn were dewormed, were not so lucky. She died. Economically, using the equine dewormer may look like a great deal. It certainly isn’t if your show dog goes blind or dies.

Other drugs affected by this MDR1 mutation include chemotherapy drugs. If your dog develops cancer, it would be nice to know if he is going to have problems with certain drugs. Your veterinarian may need to customize a protocol for your show dog or pet dog.

 

Testing for an MDR1 Mutation

Testing for this mutation in your dog can be easily done with either a cheek swab for cells that you can do yourself or a blood sample drawn by your veterinarian.

Costs are $70 for one to four tests or $60 for five or more sent together. Many local Australian Shepherd, Shetland Sheepdog and Collie clubs will organize a group order of the kits and send the tests in together for the discounted fee. Generally these groups welcome dogs of other dog breeds as well to increase the numbers. My Belgian Tervuren were all tested through a local Aussie club.

Some dogs will not need to be tested. If your dog’s parents both tested Normal/Normal, your dog will automatically be Normal. This is listed as "Normal by Parentage.”

The test is an actual gene test so results are very black and white. Dogs who are Normal/Normal don’t have the mutation and can’t pass it on. They can handle normal doses of the drugs mentioned above with no problems.

Dogs who are Mutant/Mutant can be expected to have problems with normal doses of loperamide (Immodium), doses of ivermectin over 50 mcg per kg and some chemotherapy drugs. These dogs will pass on the mutation to all of their offspring.

Dogs who test as Mutant/Normal may show some toxicity in the situations described above. They will pass the mutation onto some of their offspring.

By testing any show dogs used for breeding, and their puppies if necessary, eventually the prevalence of this gene can be decreased in a dog breed. Yes, it is a problem you can work around in most cases, but why take any unnecessary risks? I highly recommend testing any of the dog breeds listed at the very least.

 

Read more dog health articles by Debra M. Eldredge, DVM:

Emergency First-Aid Essentials
Keep these 14 must-have items in your dog’s first-aid kit. Read More>>

Advances in Lyme Disease Detection
Learn how you can protect your dogs against this deadly tick-borne disease. Read More>>

Canine Brucellosis: Disease on the Rise?
What is Canine Brucellosis and its symptoms, and how can it affect litters? Read Part 1>> and Read Part 2>

Umbilical Hernias in Dogs
An umbilical hernia is a common condition that is often overlooked. Read More>>

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Give us your opinion Give us your opinion on Problems with Dog Medications and the MDR1 Gene

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diamondgirl   w. palm beach,, Florida

5/16/2013 3:03:20 PM

i am getting a white german shepherd puppy soon. she will be 8 weeks old. do i have to test her for the MDRI gene or is there something out there safe enough to use with out this test? the parents have not been tested. i want to put her on heartworm prevention and flea/tick prevention also. thanks.

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Oliver2   Colorao Springs, CO

4/28/2013 3:48:25 PM

I've only given my Collie Interceptor. We have a compounding pharmacy in our area that formulates veterninary medicines. Also, the article noted that the problem is with the FDA and the restrictions are in the US, so Canada Drug might be another option.

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Anne   Rye, New Hampshire

3/29/2013 9:58:31 AM

I have a 6 yr. old mini-aussie who is normal/ mutant. We have always used interceptor and, of course, have had no problems. Discussing the non-availability of both this drug and sentinel with our vet we have arrived at no good conclusion. The only recommendation from the vet was to use topical revolution altho there have been problems with that drug ie: hair loss, vomiting,diarrhea and other more serious concerns in some cases. It appears that interceptor is available in Au. but whether or not it is the same drug or just the same name is unknown. There is also the consideration as to whether the online sellers are selling the REAL product. If it did not good that's one thing but it could contain harmful drugs without my knowledge.

Has anyone found any reasonable solution for this problem???

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