Overview 

Multidrug Resistance 1 (MDR1) drug sensitivity is the result of a genetic variant that can place dogs at risk of severe or life-threatening complications after taking particular medications at specific doses.  

Treatment focuses on prevention by avoiding or lowering the dosages of drugs that may cause side effects in dogs who have this genetic variant.  

Genetic testing is the most helpful tool for diagnosing MDR1 drug sensitivity.  

Cause 

MDR1 drug sensitivity occurs when dogs inherit a genetic variant in their ABCB1 gene (formerly known as the MDR1 gene). This variant causes a change in a protein called P-glycoprotein (P-gp). 

Under normal conditions, the protein helps eliminate drugs after administration and helps keep specific substances — including some drugs and toxins — out of the brain and other organs.  

However, when P-gp is not functioning correctly, these drugs and toxins can build up or even cross into the brain, causing severe and sometimes fatal reactions. 

Breed predisposition​ 

The MDR1 variant is most commonly found in herding breeds, including, but not limited to the following:  

• Collies 

• Australian Shepherds 

• American Shepherds 

• German Shepherds 

• Shetland Sheepdogs  

• Old English Sheepdogs 

Clinical signs 

The most common signs of drug toxicity in dogs with MDR1 drug sensitivity include: 

• Vomiting  

• Weakness 

• Uncoordinated movement 

• Tremors  

• Seizures   

• Blindness 

• Death 

Drugs of concern 

P-gp affects the absorption, elimination and distribution of many drugs, but only a few of these drugs can cause severe toxicity in animals with the MDR1 variant.  

For example, medications commonly used in heartworm preventatives, such as ivermectin, can cause toxicity if given in high dosages. However, heartworm preventatives are still safe for MDR1 drug-sensitive dogs to take at low, FDA-approved dosages. 

Other medications that should be used with caution and at reduced doses include sedatives like acepromazine and butorphanol, anti-cancer medications and more. One drug that should be avoided entirely is an anti-diarrheal medication called loperamide (sold under the brand name Imodium). 

Certain medications, when used in combination with each other, can increase the total concentration of individual drugs and introduce more risk of an adverse reaction — even in dogs without the genetic variant. Examples include ketoconazole, cyclosporine and spinosad (Comfortis). 

Speak with your veterinarian before changing any drug dosages or discontinuing their use. 

Diagnosis 

A variant that causes MDR1 drug sensitivity is identified by genetic testing. However, an initial diagnosis often occurs in young dogs after they have an adverse reaction to a particular drug.  

Treatment 

There is no cure or antidote for MDR1 drug sensitivity. Treatment involves decreasing drug doses to avoid adverse reactions or choosing alternate drugs altogether. Dogs with adverse drug reactions are treated based on their symptoms and supportive care.  

It is important to know that not all drug sensitivities are due to the MDR1 variant, and you should talk to your veterinarian about other concerns regarding drug sensitivity. 

Outcome 

With proper consideration of drug interactions and dosages, MDR1 drug-sensitive dogs can live normal lives without incident.  

Severe and potentially life-threatening consequences can occur if drugs are taken at incorrect dosages, if they are used in certain combinations with other drugs or if at-risk dogs are unintentionally exposed to problem drugs (e.g. ivermectin used to deworm horses).  

Genetics 

The ABCB1 gene encodes P-glycoprotein, determining its base-level functionality. A dog may be severely affected by drug sensitivity if they inherit two copies of the ABCB1 variant, giving them only an abnormal P-gp. Dogs can still experience drug toxicity even with just one copy of the variant, but the effects are generally less severe. 

Because MDR1 drug sensitivity can be easily managed after it is identified, the elimination of all dogs with this variant from a breeding program is not recommended. 

This health topic was developed as part of a collaboration between the Cornell Richard P. Riney Canine Health Center and Embark Veterinary, Inc. You can learn more about the hereditary risks of other canine health conditions by exploring our genetics articles.