Ivermectin Sensitivity in White Shepherds

There are two commonly used dosage levels for ivermectin in dogs. The lower dosage is used to prevent heartworm infection and is found in Heartguard and Heartguard Plus monthly tablets and chews. This product is sold by prescription only and the tablets are sold in various sizes and labeled according to the dog's weight. According to the manufacturer, there has never been a documented ivermectin sensitivity reaction to this dosage. Heartworm prevention products containing ivermectin that are labeled for dogs are perfectly safe for all White Shepherds. Heartguard and Heartguard Plus are the only brand names of these products that I know of. The dosage of ivermectin needed to prevent heartworms is almost microscopic in these products and even a dog with proven sensitivity will not have a reaction to them.  A Monthly heartworm preventive without ivermectin would be "Interceptor".

The higher dosage of ivermectin that is used (even by veterinarians) for treating mange and intestinal worms is 50-100 times the dosage needed to prevent heartworms. The higher dosage is often used to treat mange mites and intestinal worms and the typical product used is 'Ivomec', a 1% solution of ivermectin labeled for injectable use to control parasites in cattle. This product is typically administered orally at 1 ml per 100 lbs of dog. That would be 1/10th ml per 10 lbs. There is also a generic ivermectin 1% solution available. 'Ivomec' ivermectin also comes in a less concentrated 0.27% solution labeled for injectable use in grower/feeder pigs.

Ivermectin also comes in a more concentrated paste wormer for horses. The horse paste wormer has been marketed under several brand names including "Zimectrin" and "Eqvalan". The paste is much too difficult to measure accurately in small doses and should never be used for dogs. If in doubt, just read the ingredients on the label. These products are NEVER labeled for dogs. Although these products are available without a prescription, and are much cheaper than heartguard, using any of these products for treating dogs is an "off label" use and the user assumes all risk of overdose and possibly fatal reactions.

I have personal knowledge of several cases of ivermectin sensitivity at the higher dosage. With mild reactions, a dog will act droopy and uncoordinated for a few hours up to a couple of days after treatment. With moderate reactions, a dog will go into a coma-like state for a few days and then (if given adequate supportive care) recover fully. A dog with a severe reaction will die. I know of 2 dogs with mild reactions, 2 dogs with moderate reactions, and 2 dogs who died. Three of these 6 dogs were daughters of Gozer the Destroyer. Two more are descendants of Gozer. One seems to be unrelated. That seems to be too much relationship to Gozer to be coincidence. I believe the sensitivity to high doses of ivermectin to be inherited. I don't know the mechanism yet, whether it is a single gene, polygenic, recessive or dominant. Perhaps if we pool our experiences, we can determine that. There are likely several bloodlines with affected dogs who have not had the higher dose of ivermectin that would reveal a sensitivity, so be very careful.

Reactions are rare. In more than 10 years of using liquid ivermectin on dozens of dogs, I have seen only these few cases. If you use liquid ivermectin, the solution to the problem of sensitivity is a simple one. Use the smaller dose for heartworm prevention, not the higher dose for mites & worms. This dosage would be just a few drops of the liquid ivermectin each month. If you have more than a couple of dogs and live in an area with mosquitoes, the value of an economical heartworm preventive outweighs the risk in my opinion. If you have a problem with mites, or intestinal worms and want to use ivermectin for treating them, then use just a third of a dose and monitor the dog for a day or two. If the dog is sensitive, you might see symptoms, and know not to ever give that dog a full dose at the higher level. If you don't see any symptoms, make the next dose 2/3 of a full dose and then monitor again.

The Pro-heart 6 product is an injectable heartworm preventive that is given once every 6 months. The active ingredient is related to ivermectin. I do not know if a dog with an ivermectin sensitivity would react to this product or not. To be on the safe side, I would not try it if you had not given ivermectin to that dog at the higher dosage in the past (and proven the dog to tolerate it OK).

Here are the affected dogs that I know about:
Mansha's Midnite Sumers Magic, sire Gozer the Destroyer, dam Mansha's Magical Mystery Tour
Tumbledown's Tyrian Purple, sire Gozer the Destroyer, dam Hytymes Zanadau Tumbledown
Tumbledowns Gettysburg, sire Gozer the Destroyer, dam Phoenix of Tumbledown
Regalwise Coming Ruler, sire Tumbledown's Toreador, dam Regalwise True Silver v Royalair
"Chico", sire Tumbledown's Toreador, dam Regalwise Stellar
"Sugar", sire Tumbledown's Super Sonic, dam Tumbledown's Mariah's Blaze

Molecular biological research is proving that many herding breed dogs
have a genetic mutation called MDR1 - multiple drug resistance deficiency.
In sum, the barrier (P-glycoprotein) that protects the brain by
transporting a variety of drugs from the brain tissues back into the
capillaries is flawed. This is the root cause of the disastrous
neurological effects, including death, caused by the ingestion of
ivermectin. But, IT'S NOT JUST IVERMECTIN (also known as Avermectin,
and the anti-parasitic used in the trade name drug Heartguard and
commonly used to treat demodic mange).

It's also almost certainly these drugs (alternate names, common usage,
and trade names follow the generic name): 

Metronidazole (diarrhea and giardia):Flagyl; Rozex; Metrogel
Butorphanol (pain relief after spay/neuter; cough suppressant and canine
flu): Torbutol; Butorphic; Dolorex; Morphasol; Turbogesic
Acepromazine (tranquilizer/calming agent and pre-anesthetic): Ace; ACP; Atravet
Cyclosporine or Ciclosporin (allergy treatment/immunosuppresant): Sandimmune; Neoral; Cicloral; Gengraf; Restasis
Vinblastine and Vincristine (chemotherapy for cancers & leukemia): cancer regimens called CHOP and Stanford V 
Doxurobicin or Adriamycin or Hydroxyldaunorubicin (chemotherapy for
cancers & leukemia): Doxil; cancer regimens called ABVD, CHOP, and FAC
Loperamide (diarrhea): Imodium; Lopex; Dimor; Pepto
Digoxin (heart ailments): Digitalis (Foxglove) family

Additionally, neurotoxicity in dogs with the MDR1 genetic flaw is
suspected to have been caused by: 

Ondansetron (nausea and vomiting): Zofran; Emeset; Emetron; Ondemet 
Domperidone (nausea, vomiting, and to stimulate lactation): Motilium
Paclitaxel (cancer): Taxol; Abraxane
Mitoxantrone (cancer/leukemia)
Etoposide (cancer/leukemia): Eposin; Etopophos; Vepeside; VP-16
Rifampicin or Rifampin (antibiotic - infections, influenza, pneumonia,
staph, meningitis): Rifadin; Rifater; Rimactane; Rifinah; Rimactazid
Quinidine (heart)
Morphine (pain relief, anesthesia, cough suppressant, anti-diarrheal,
shortness of breath)
Although any errors or omissions in the above are solely my doing , the
credit for most of this information goes to:
Washington State University College of Veterinary Medicine 
Veterinary Clinical Pharmacology Laboratory
PO Box 2280,  Pullman, WA 99165-2280   
(Phone/FAX 509-335-3745)  VCPL@vetmed.wsu.edu
You can learn more about the MDR1 defect and about testing your herding
breed dog by going to their website: http://www.vetmed.wsu.edu/depts-VCPL/

Do not leave it up to your vet to know this ... YOU must print this
out and know about MDR1 ... it IS a matter of life or death. 

Ronda Beaupre