Problem Drugs
Many different drugs and drug classes have been reported to cause problems in
Collies and other herding breed dogs that carry the MDR1 mutation. We and other
researchers have documented the toxicity that occurs with several of these
drugs.
Drugs that have been documented to cause problems in dogs with the MDR1
mutation include:
- Acepromazine (tranquilizer and pre-anesthetic agent). In
dogs with the MDR1 mutation, acepromazine tends to cause more profound and
prolonged sedation. We recommend reducing the dose by 25% in dogs heterozygous
for the MDR1 mutation (mutant/normal) and by 30-50% in dogs homozygous for the
MDR1 mutation (mutant/mutant).
- Butorphanol (analgesic and pre-anesthetic agent). Similar
to acepromazine, butorphanol tends to cause more profound and prolonged sedation
in dogs with the MDR1 mutation.We recommend reducing the dose by 25% in dogs
heterozygous for the MDR1 mutation (mutant/normal) and by 30-50% in dogs
homozygous for the MDR1 mutation (mutant/mutant).
- Emodepside (Profender�)-is a
deworming drug approved for use in cats only in the U.S., but is approved for
use in dogs in some other countries. Use of this drug in dogs with the MDR1
mutation has resulted in neurological toxicity.
- Erythromycin. Erythromycin may cause neurological signs in
dogs with the MDR1 mutation. A mutant/mutant collie exhibited signs of
neurological toxicity after receiving erythromycin. After withdrawal of the
drug, the dogs neurological signs resolved. There were no other potential
causes of neurological toxicity identified in the dog.
- 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 (mutant/mutant) and can cause toxicity in
dogs that are heterozygous for the mutation (mutant/normal).
- 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.
- 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.
- Vincristine, Vinblastine, Doxorubicin (chemotherapy
agents). Based on some published and ongoing research, it appears that dogs with
the MDR1 mutation are more sensitive to these drugs with regard to their
likelihood of having an adverse drug reaction. Bone marrow suppression
(decreased blood cell counts, particulary neutrophils) and GI toxicity
(anorexia, vomiting, diarrhea) are more likely to occur at normal doses in dogs
with the MDR1 mutation. To reduce the likelihood of severe toxicity in these
dogs, MDR1 mutant/normal dogs should have their dose reduced by 25% while MDR1
mutant/mutant dogs should have their dose reduced by a full 50%. These patients
should be closely monitored for adverse effects.
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 may be pumped out by the protein that the MDR1 is responsible for
producing, but appear to be safely 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
- Paclitaxel
- 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.
