MDR1 Medication Sensitivity

Dogs with this variant are asymptomatic until exposed to a medication that uses the drug transport pump rendered defective by the mutation in the MDR1 (also called ABCB1) gene. Medications known to use this P-glycoprotein pump are macrocyclic lactones (antiparasitic drugs), loperamide (antidiarrheal), erythromycin (antibiotic), acepromazine (tranquilizer), butorphanol (opioid), certain drugs used in cancer treatment (vincristine, vinblastine, and doxorubicin), and others. When these medications are administered, they accumulate in the brain which results in adverse reactions. Typical symptoms include tremors, loss of balance, seizures, obtundation, excessive salivation, dilated pupils, and bradycardia. If untreated, the condition may lead to respiratory arrest, coma or death. Because dogs with 1 copy of the variant will have some P-glycoprotein function, the most severe cases tend to occur in dogs that have 2 copies of the variant and, therefore, lack any functional P-glycoprotein pumps. However, the disorder can still be very severe in dogs that have only one copy of the mutation.

For dogs with the MDR1 variant, it is important to be aware of medications which may result in an adverse reaction. These include: Acepromazine, Afoxolaner, Apomorphine, Butorphanol, Cyclosporin, Doxorubicin, Doramectin, Emodepside, Erythromycin, Fluralaner, Grapiprant, Ivermectin, Loperamide, Maropitant, Milbemycin, Moxidectin, Ondansetron, Paclitaxel, Rifampin, Sarolaner, Selamectin, Vinblastine, Vincristine, Vinorelbine. It is best to explore alternative medications that will not use this P-glycoprotein pump or, at minimum, consider reduction of the dose to levels safe for an MDR1 positive dog. Please note, all FDA approved heartworm preventatives have undergone product safety testing at the label doses for dogs with one and two copies of the MDR1 variant, and none reported adverse effects at the labeled dose. However, if the antiparasitics are used at higher or more frequent dosing – such as to treat heartworm disease or ectopic parasites like sarcoptic mange – adverse effects can occur. Additionally, the combination of two or more of the listed medications can lead to adverse reactions even if the medications are tolerated when given alone.

There are many responsibilities to consider when breeding dogs. Regardless of test results it is important that your dog is in good general health and that you are in a position to care for the puppies if new responsible owners are not found. For first time or novice breeders, advice can be found at most kennel club websites.

This disorder is autosomal dominant meaning that only one copy of the variant is needed for associated signs to occur. For some breeds where the MDR1 mutation frequency is particularly high, breeders may consider mating pairs using dogs that have one or two copies of the MDR1 variant to maintain genetic diversity within their breed. It is important that resulting puppies be tested for the MDR1 variant to ensure safe future medical treatment. If a dog with one copy of the MDR1 variant is bred with a clear dog with no copies of the MDR1 variant, about half of the puppies will have one copy and half will have no copies of the MDR1 variant. If a dog with two copies of the MDR1 variant is bred with a clear dog, the resulting puppies will all have one copy of the variant. Please note: It is possible that clinical signs similar to the ones caused by the MDR1 variant could develop due to a different genetic or clinical cause.