The MDR1 Mutation - What it is and why you need to know!

Most dogs tolerate chemotherapy very well. The majority (75-80%) will not have side effects, but a small percentage (20-25%) will develop soft stool or nausea approximately 2-4 days after receiving treatment. If early signs of nausea (such as decreased appetite, drooling, lip smacking) are recognized and treated appropriately, then vomiting can usually be avoided (which is the goal).

In most cases, we cannot predict which dogs will develop nausea or soft stool - we wish we could! However, some dogs carry a genetic mutation which makes them more likely to experience significant side effects from certain chemotherapy agents. Dogs that have this mutation, called the MDR1 mutation, shouldn't receive these "problem" chemotherapy agents or should receive them at a significantly reduced dose.

MDR stands for multidrug resistance. Dogs with an MDR1 mutation are unable to process certain medications normally, so they stay in the body for a longer time and the patient can develop signs of an overdose. Depending on the medication, these signs can include neurologic signs or severe vomiting and diarrhea requiring hospitalization.

Dogs with an MDR1 mutation should either not receive or receive significant dose reductions of the medications from the "problem drug" list below; there are different recommendations depending on the medication and whether the patient has 1 or 2 copies of the mutant gene.

You'll notice that the medications on the lists below are not just chemotherapy medications.

Medications that can cause toxicity in MDR mutants

(1) Sedatives: acepromazine, butorphanol
(2) Antidiarrheals: loperamide (Imodium)
(3) Emetic (induces vomiting): apomorphine
(4) Chemotherapeutic: vincristine, vinblastine, doxorubicin, Paclitaxel
(5) Ivermectin (Heartgard): safe at heartworm prevention dose, toxic at higher doses
(6) Antiparasitics: milbemycin (Sentinel, Trifexis, Interceptor), selamectin (Revolution), moxidectin (Advantage multi) **Note: According to research from WSU, these drugs are safe when used at the recommended dose, but can cause neurologic toxicity when given at 10-20 times the heartworm prevention dose

Which dog breeds are at risk?

Below I have listed breeds that have been reported to have the MDR1 mutation, as well as the frequency at which the mutation is thought to occur.  

Australian Shepherd 50%
Mini Australian Shephard 50%
Black Mouth Cur (unknown frequency)
Border Collie <5%
Carolina Dog (unknown frequency)
Chinook 25%
Collie 70%
English Shepherd 15%
German Shepherd 10%
Herding breed cross 10%
Long-haired Whippet 50%
McNab 30%
Mixed breed 5%
Old English Sheepdog 5%
Shetland Sheepdog 15%
Silken Windhound 30%
 
How is testing performed?

Testing is performed at Washington State University. They are able to collect DNA using a blood sample (via FedEx) or a cheek swab.  If you are interested in using a cheek swab, they can send out a special collection kit; this is a test that you can do at home and send in yourself (there are instructional videos on their website).

If you need an answer quickly because your vet/oncologist needs to know MDR status for chemotherapy purposes, a blood test should be submitted unless they already have cheek swab kits on hand at their clinic.

PCR (polymerase chain reaction) is used for this DNA test, which is very tedious. All samples at Washington State are batched on Monday and results are released every Friday (no exceptions). They don't offer a STAT or rush option.

If you are interested in learning more about sample collection or the lab itself: Washington State Veterinary Clinical Pharmacology Lab

 If you have a breed that is known to carry the MDR1 mutation, consider having him tested to determine if he has the mutation. If you submit this test to WSU yourself the cost is $60 plus shipping. 

If your dog is on the "problem breed" list and you don't know his mutation status, keep the "problem drug" list in mind when you are at the vet clinic. Just be sure that his clinician keeps his unknown mutation status in mind when choosing which dose and medication to administer.

 

Have questions about this article? Reach out!
Dr. Lori Cesario
Board Certified Veterinary Oncologist
lori@caninecanceracademy.com 


A few other articles you might enjoy...

(1) Osteosarcoma - The #1 bone cancer in dogs
(2) Mast Cell Tumors - The Great Imitator in Canine Cancer
(3) Canine Splenic Tumors - What You Need To Know

 

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