Drug Sensitivity

Some dogs within certain herding breeds carry genetic mutations that cause them to be sensitive to certain drugs. At this time, the affected breeds are: Australian Shepherds, Collies, German Shepherds, Long haired Whippets, Miniature American Shepherds, Old English Sheep dogs, Shetland Sheep dogs, and Silken Windhounds. Research in molecular biology discovered the Multi-drug Resistance1 Gene (MDR1) encodes a protein (P-glycoprotein) that is responsible for limiting drug absorption and expelling drugs/toxins from the dog's brain. Dogs with the mutant genes have a compromised blood brain barrier and cannot pump certain drugs from their brain tissues as a normal dog would. If improperly handled, it could be serious and possibly result in their death. As research continues, more breeds and different drugs may be added to this list.

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Washington State University has developed a test to screen for the presence of the mutant MDR1 Gene. Several other companies also now offer screening for the MDR1 gene.

Dogs that are AFFECTED by MDR1 exhibit sensitivity to Ivermectin and other related drugs.

Dogs that are CARRIERS of MDR1 may experience some sensitivity to Ivermectin and other related drugs.

Dogs that are clear of MDR1 should not exhibit any drug sensitivities.

Dogs that have not been tested or (status unknown) should avoid the following list of drugs.

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Documented drugs that cause health issues in dogs with the MDR1 mutation gene are:

Acepromazine (A tranquilizer or pre-anesthetic agent)

Butorphanol (An Analgesic and pre-anesthetic agent)

This drug is similar to Acepromazine, but induces a more profound and prolonged sedation in dogs with the MDR1 mutation gene.

Emodepside (Profender is a de-worming drug)

Erythromycin (A macrolide antibiotic used to treat bacterial infections)

Ivermectin (An anti-parasitic agent)

Loperamide (Imodium TM anti-diarrheal medicine)

Selamectin, Milbemycins, and Moxidectin (Anti parasitic agents)

Like Ivermectin, these drugs are safe for use in dogs with the MDR1 mutation if used in heartworm preventative according to the Manufacturer's recommended dosage. If the dose is increased (10 to 20 times higher than the heartworm preventative dose), dogs with the MDR1 mutation will experience neurological toxicity.

Vincristine, Vinblastine, Doxorubicin (chemotherapy drugs)

Cyclosporine (An immunosuppressive agent)

Cyclosporine is pumped by P-glycoprotein (the protein encoded by the MDR1 gene).

Digoxin (cardiac drug)

Digoxin is pumped by P-glycoprotein (the protein encoded by the MDR1 gene). There is no documentation of increased sensitivity to this drug in dogs with the MDR1 mutation, compared to normal dogs. Recommend therapeutic drug monitoring.

Doxycycline (antibacterial drug)

Doxycycline is pumped by P-glycoprotein (the protein encoded by the MDR1 gene). There is no documentation of increased sensitivity to this drug in dogs with the MDR1 mutation, compared to normal dogs. It is not recommended to alter the dose of Doxycycline for dogs with the MDR1 mutation, and therapeutic drug monitoring is important.

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Drugs that may be pumped out by the protein that the MDR1 is responsible for producing but appear to be safely tolerated by dogs with the MDR1 mutation.

Morphine, Buprenorphine, Fentanyl (opioid analgesics and pain medication)

These drugs are pumped by P-glycoprotein (the protein encoded by the MDR1 gene) in dogs because they have been reported to be pumped by P-glycoprotein in people. We are not aware of toxicity reports caused by these drugs in dogs with the MDR1 mutation.

The following drugs have been reported to be pumped by P-glycoprotein (the protein encoded by the MDR1) in humans.

There is no current data stating whether they are or not pumped by canine P-glycoprotein.

Caution should be used when administering these drugs to dogs with the MDR1 mutation.

Domperidone, Etoposide, Mitoxantrone, Ondansetron, Paclitaxel, Rifampicin

Research indicates that other drugs have been shown to be pumped by the human P-glycoprotein which is the protein encoded by the MDR1 gene, however current data is not available in reference to their effect on dogs with the MDR1 mutation. 

Veterinary Clinical Pharmacology Laboratory
PO Box 609
Washington State University
Pullman WA 99163-0609
509-335-3745

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