The MDR1 Genetic Deletion in Dogs

Problem Drugs

Many different drugs and drug classes have been reported to cause problems in dogs with the MDR1 mutation. The

University of Washington Veterinary Clinical Pharmacology Lab (http://vcpl.vetmed.wsu.edu ) continues to work to

identify drugs that may be dangerous to dogs with the MDR1 mutation and to determine alternative drugs and doses

for these dogs.

Drugs that have been documented to cause problems in dogs with the MDR1 mutation include:

Ivermectin (antiparasitic agent) - While the dose of ivermectin used

to prevent heartworm infection (Heartgard®, Iverheart®, Triheart®,

mutant/normal).

Selamectin, milbemycin, and moxidectin (antaparasitic agents) -

Similar to ivermectin, these drugs are safe in dogs with the

mutation if used for heartworm prevention at the manufacturer’s recommended dose (Revolution®, Interceptor®,

Sentinel®, Trifexis®, ProHeart®, Advantage Multi®). Higher doses (generally 10-20 times higher than the heartworm

prevention dose) have been documented to cause neurological toxicity in dogs with the MDR1 mutation.

Loperamide (Imodium

TM

; antidiarrheal agent) - At doses used to treat diarrhea, this drug will cause neurological

toxicity in dogs with the MDR1 mutation. This drug should be avoided in all dogs with the MDR1 mutation.

Acepromazine (tranquilizer and pre-anesthetic agent) - Based on collaborative research, the VCPL has determined

Apomorphine - this drug is used to induce vomiting in dogs that have ingested poisons/toxins. It can cause central

nervous system depression in dogs with the MDR1 mutation at standard doses.

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:

Cyclosporin (Atopica®, Sandimmune® - immunosuppressive agent) - While we know that cyclosporin is pumped by

P-glycoprotein (the protein encoded by the MDR1 gene), we have not documented any increased sensitivity to this

drug in dogs with the MDR1 mutation compared to “normal” dogs. Therefore, we do not recommend altering the

dose of cyclosporin for dogs with the MDR1 mutation, but we do recommend therapeutic drug monitoring.

Digoxin (cardiac drug) - While we know that digoxin is pumped by

pumped by P-glycoprotein (the protein encoded by the MDR1

gene), we have not documented any increased sensitivity to this

drug in dogs with the MDR1 mutation compared to “normal” dogs.

Therefore, we do not recommend altering the dose of doxycycline

for dogs with the MDR1 mutation.

Morphine, buprenorphine, fentanyl (opioid analgesics or pain medications) - We suspect that 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, but we are not aware of any reports of toxicity caused by these drugs in dogs

with the MDR1 mutation. We do not have specific dose recommendations for these drugs for dogs with the MDR1

mutation.

 Ondansetron

 Rifampicin

There are many other drugs that have been shown to be pumped by human P-glycoprotein (the protein encoded by

the MDR1 gene), but data is not yet available with regard to their effect in dogs with the MDR1 mutation.

MDR1 Breeding Guidelines

This chart provides guidelines for consideration when owners are contemplating breeding dogs that may be affected

by the MDR1 mutation. While it is ideal to use only "Normal/Normal" breeding pairs, one must always consider

other genetic factors in addition to the MDR1 gene. Because the MDR1 gene is present in such a large percentage

of Collies and Australian Shepherds, it may be necessary to breed "Normal/Mutant" dogs in order to maintain a large

enough pool of good breeding stock. By using thoughtful breeding strategies including these guidelines, future

Normal/Normal Female

Normal/Mutant Female