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 (standard, mini, and toy), Collies, German Shepherds, Long haired Whippets, 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.

Washington State University has developed a test to screen for the presence of the mutant MDR1 Gene.

For more information Click on the link MDR1 Canine Gene Mutation

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.

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

Acepromazine (A tranquilizer or pre-anesthetic agent)

If administered to a dog with MDR1 mutation, Acepromazine tends to cause a more profound and prolonged period of sedation. We recommend reducing the dose by 25% for heterozygous dogs with MDR1 (mutant/normal) mutation and by 30 to 50 % homozygous dogs with MDR1 (mutant/mutant) mutation.

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. It is recommended to reduce the dose by 25% for and by 30 to 50 % homozygous dogs with MDR1 (mutant/mutant) mutation.

Emodepside (Profender is a de-worming drug approved for cat use only within the US)

Other countries have also approved it for use in dogs. If used for dogs with the MDR1 mutation, neurological toxicity may result.

Erythromycin (A macrolide antibiotic used to treat bacterial infections)

If used for dogs with the MDR1 mutation, neurological toxicity may result.

Ivermectin (An anti-parasitic agent)

When Ivermectin is used in the monthly heart worm preventative; it is safe for dogs with the MDR1 mutation. (6micrograms per kilogram) or higher doses, such as those used for treating mange (300 -600 micrograms per kilogram) may cause toxicity in heterozygous dogs with MDR1 (mutant/normal) mutation and will cause neurological toxicity in homozygous dogs with MDR1 (mutant/mutant) mutation.

Loperamide (Imodium TM anti-diarrheal medicine)

This drug should be avoided for dogs with the MDR1 mutation. If used it will cause neurological toxicity in homozygous dogs with MDR1 (mutant/mutant) mutation.

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)

Based on published and ongoing research, dogs with the MDR1 mutation are more sensitive to these drugs and may experience more adverse drug reactions. Bone marrow suppression (decreased blood cell counts, particularly neutrophils) and GI toxicity (anorexia, vomiting, and diarrhea) are more likely to occur at normal doses in dogs with the MDR1 mutation. To reduce the likelihood of severe toxicity in these dogs (mutant/normal or mutant/mutant), it is recommended to reduce the dose by 25 to 30% and carefully monitor the patient.

Drugs that are known to be pumped out of the brain by the protein that the MDR1 gene is responsible for producing, but appear to be safely tolerated by dogs with the MDR1 mutation.

Cyclosporine (An immunosuppressive agent)

Cyclosporine 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. We do not recommend altering the dose of cyclosporine for dogs with the MDR1 mutation, however recommend therapeutic drug monitoring.

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. We do not recommend altering the dose of Digoxin for dogs with the MDR1 mutation, however 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.

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
 

MDR1 Canine Gene Mutation