| Ivermectin was introduced during the 1980's as a vaccine for worming and mange treatment in cattle and pigs. Despite not being licensed in the UK for use in dogs, some vets had used it successfully on many breeds, but unfortunately there had been some fatalities in Collies and related breeds. During the late 80's a UK Collie breeder sadly lost two Collies to Ivermectin poisoning and following discussions with the manufacturers a warning has since been added to the labelling: "Ivomec Injection for cattle is a low volume product registered for use in cattle. It should not be used in other species as severe adverse reactions, including fatalities in dogs, may occur." (a similar warning was also added to the package insert of Ivomec Injection for pigs). Resulting from other fatalities across Europe, UK and America, research into the canine multi-drug resistance gene (MDR1) has been ongoing at several University Veterinary Departments, the results of which are now in the public domain.
MDR1 is part of the canine blood-brain barrier and acts as a multi-drug transporter, being responsible for limiting the penetration of a range of drug compounds into the brain. Researchers found that certain breeds of dog, mainly Rough (50%) and Smooth Collies, Border Collies, Australian Shepherds, Long-haired Whippets, McNab Sheherd dogs, Old English Sheepdogs, Shetland Sheepdogs and Silken Windhounds, have a tendency to inherit a defective or mutant MDR1 gene which causes the MDR1 drug transporter to mal-function. Since Kate Mealey and Mark Neff’s research into the multi-drug sensitivity of certain breeds was made public in 2004 (School of Veterinary Medicine, University of California, Davis), similar research is ongoing in Germany, Switzerland and Australia. The MDR1 gene defect is inherited as an autosomal recessive condition. Affected dogs are homozygous for the condition (MDR1/MDR1 or -/-) and can only receive a defective MDR1 gene from each of its parents. Such animals will display toxic reactions to a range of drugs, as excessive amounts are absorbed through the blood-brain barrier into their brains. For instance, in cases of Ivermectin poisoning, affected dogs exhibit excessive salivation, ataxia, blindness, coma, respiratory problems, and even death. ‘Carriers’ are heterozygous for the condition and, as such, are classified as N/MDR1 or +/-). The laboratory interpretation of a carrier animal states: "The analysed dog is a carrier of the mutation in the MDR1-gene that has been shown to cause hypersensitivity towards certain drugs such as Ivermectin. The dog will not develop Ivermectin sensitivity caused by this mutation, but will pass the defect gene onto its offspring with a probability of 50%." It is therefore most important to detect carriers before they are used for breeding. MDR1 normal dogs (N/N or +/+) are homozygous for the condition, and can only pass on a healthy MDR1 gene to their offspring. Such animals do not exhibit drug toxicity. Since the Mealy/Neff research, the components of several other drugs (thought to be safe a few years ago) have since been found to cause toxicity to MDR1 affected (-/-) dogs. The table below shows those drug compounds that are currently known to cause problems in affected Collies: Class A | DO NOT USE in dogs with MDR1 defect. An affected dog (-/-) carries two mutant MDR1 genes so can only pass on a mutant gene to its offspring. Affected dogs will experience drug toxicity following normal doses of those drugs listed here: | Ivermectine substances: Diapec®, Ecomectin®, Equimax®,Eqvalan®, Ivomec®, Noromectin®, Paramectin®, Qualimec®, Sumex® & Virbamec® Doramectine substances: Dectomax® Moxidectine substances: Cydectin® & Equest® Loperamide substances: Immodium®
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Class B
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Interactions have been shown. Use only under close supervision of your vet
| Cytostatics: Vinblastine, Doxorubicine, Paclitaxel, Docetaxel, Methotrexat & Vincristine Immuno-suppressives: Cyclosporine A Heart glycosides: Digoxine & Methyldigoxine Opioids: Morphium Antiarrhythmics: Verapamil, Diltiazem & Chinidine Anti-emetics: Ondansetron & Domperidon Antibiotics: Sparfloxacin, Grepafloxicin Antihistamines: Ebastin
Glucocortisoids: Dexamethason
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Class C
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Can be used
| Stronghold®, Advocate® & Milbemax® can be used only in the recommended application and dosage. |
The importance of knowing your Collie's MDR1 status cannot be over-emphasised, as you never know when he or she may require surgery and/or drug treatment. If your dog is known to be affected (-/-), you will at least be in a position to inform your vet of the dangers of certain drugs, by printing off the information above. The Laboklin Laboratories of Manchester (UK branch of the Laboklin Company of Bad Kissingen, Germany) now offer a DNA test for MDR1, using a simple buccal swab which identifies normal, affected and carrier animals. Collies can be tested at any age. June 2007. References: Veterinary Clinical Pharmacology Laboratory, Washington State University,
'Ivermectin Revisited', The International Collie Society's Handbook 2004, & 'MDR Update', ICS H'bk 2007/8 | 
