Problem Drugs
     
      Many different drugs and drug classes have been reported to cause  problems in dogs with the MDR1 mutation.  The VCPL 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 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).
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)-  Based on collaborative research, the VCPL has determined that 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)-  Based on collaborative research, the VCPL has determined that dose  reductions are required for dogs MDR1 mutant/mutant and MDR1  mutant/normal in order 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.      
     


     
     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 (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 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  digoxin for dogs with the MDR1 mutation, but do recommend therapeutic  drug monitoring.
Doxycycline (antibacterial drug)-  While we know that doxycycline 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  doxycycline for dogs with the MDR1 mutation.     
     


     
     Drugs that are known to be transported  by the human or rodent forms of the protein encoded by the MDR1 gene  but appear to be tolerated by 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.
The following drugs have been reported  to be pumped by P-glycoprotein (the protein encoded by the MDR1) in  humans, but there is currently no data stating whether they are or are  not pumped by canine P-glycoprotein.  Therefore we suggest using caution  when administering these drugs to dogs with the MDR1 mutation. 
Domperidone  
Etoposide  
Mitoxantrone  
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.