What is multidrug sensitivity?
Some dogs and cats have a mutation in the MDR1 (multidrug resistance 1) gene also known as the ABCB1 gene, which plays an important role in limiting drug distribution to the brain and in enhancing the excretion of many drugs. Animals with the mutation may have severe adverse reactions – including tremors, disorientation, blindness, lack of muscle control, and death – to some common drugs.
How common is the MDR1 mutation?
It can occur in up to 75% of some dog breeds and it affects 4% of all cats. Herding breeds, like collies and Australian shepherds, and long-haired whippets, have the highest occurrences. It is also found in Shetland sheepdogs (shelties), old English sheepdogs, English shepherds, German shepherds, silken windhounds, and a variety of mixed breeds.
Which drugs should I be concerned about?
Many different drugs and drug classes have been reported to cause problems in dogs with the MDR1 mutation. Drugs that have been documented to cause reactions include:
- Ivermectin (antiparasitic agent) While the dose of ivermectin used to prevent heartworm infection is safe in dogs with the mutation (6 micrograms per kilogram), higher doses, such as those used for treating mange (300-600 micrograms per kilogram), will cause neurological toxicity in dogs that are homozygous for the MDR1 mutation (MDR1 mutant/mutant) and can cause toxicity in dogs that are heterozygous for the mutation (MDR1 mutant/normal).
- Eprinomectin (antiparasitic agent) Cats with the MDR1 mutation have experienced severe neurological toxicity and death after being treated with a monthly heartworm preventive containing eprinomectin. In contrast to dogs, these adverse effects occurred when the product was used at the manufacturer’s recommended label dose.
- 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. 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 (ImodiumTM; 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) Dose reductions are required for dogs MDR1 mutant/mutant and MDR1 mutant/normal.
- Butorphanol (analgesic and pre-anesthetic agent) Dose reduction required for dogs MDR1 mutant/mutant and MDR1 mutant/normal.
- Chemotherapy agents (Vincristine, Vinblastine, Doxorubicin, Paclitaxel) Dose reductions are required for dogs MDR1 mutant/mutant and MDR1 mutant/normal to avoid severe toxicity.
- 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.
How do I find out if my animal has the MDR1 mutation?
Our team at WSU has developed a test that can tell you if your pet has the MDR1 gene mutation.
Why should I get my test from WSU?
WSU researchers made the initial discoveries of both the canine and feline MDR1 mutations and were the first to develop diagnostic tests to determine an individual animal’s MDR1 genotype. Scientists at WSU continue to conduct research to identify problem drugs.