Veterinary Medicine - August 2008 - (Page 456)

Demodicosis PEER-REVIEWED TABLE 6 TABLE 7 Example of Incrementally Increasing the Dose of Ivermectin in a Dog Patient: Not a classic breed for ivermectin sensitivity Body weight: 44 lb (20 kg) Ivermectin formulation: 1% solution Ivermectin conversion to mg/ml: 1 g/100 ml = 1,000 mg/100 ml = 10 mg/ml Initial ivermectin target dose: 400 µg/kg/day (20 kg) = 8,000 µg/day Initial ivermectin volume: 8,000 µg (1 mg/1,000 µg) (ml/10 mg) = 0.8 ml Initial ivermectin administration: Days 0–2: 0.2 ml (25% of total ivermectin volume) Days 3–5: 0.4 ml (50% of total ivermectin volume) Days 6–8: 0.6 ml (75% of total ivermectin volume) Day 9+: 0.8 ml (100% of total ivermectin volume) Selected P-Glycoprotein Inhibitors* Antidepressants Fluoxetine Paroxetine St. John’s wort Antimicrobials Erythromycin Itraconazole Ketoconazole Opioids Methadone Pentazocine Cardiac drugs Amiodarone Carvedilol Nicardipine Quinidine Verapamil Immunosuppressants Cyclosporine Tacrolimus Miscellaneous Bromocriptine Chlorpromazine Grapefruit juice Tamoxifen *Source: Reference 22. dosing ivermectin at 50 µg/kg/day and then incrementally increasing the dose by 50 µg/kg during the rst days of treatment until the target dose is achieved.19 Another way to gradually increase the dose of ivermectin is to calculate the target dose and corresponding volume, and then give 25%, 50%, and 75% of the total volume for several days before reaching the therapeutic volume (Table 6). Because of the long half-life of the drug, ivermectin serum concentrations increase for weeks with daily dosing. Thus, patients need to be monitored for side effects during the rst several weeks to months of therapy.10 The pour-on formulation of ivermectin is not effective in treating generalized demodicosis.10 Signs of ivermectin toxicosis can occur in any breed but are most common in ivermectin-sensitive breeds such as collies and other herding breeds.20,21 Ivermectin sensitivity is derived from a frameshift deletion mutation of the multidrug resistance gene (MDR1; the most recent nomenclature is ABCB1), resulting in a severely truncated, nonfunctional protein product. The product of the MDR1 gene, P-glycoprotein, is a large ATP-dependent transmembrane protein transporter found in the blood-brain barrier among other tissues.22 P-glycoprotein pumps substrates (e.g. ivermectin and loperamide) within the brain back into the blood. Dogs ho- mozygous for this mutation (MDR1-1 delta) display an ivermectin-sensitive phenotype, developing severe neurotoxicosis after a single dose of ivermectin.22 When ivermectin is deemed necessary for a dog, testing for the MDR1-1 delta genotype before its use is available through Washington State University’s Veterinary Clinical Pharmacology Laboratory (www .vetmed.wsu.edu/vcpl). Dogs without an ivermectin-sensitive genotype can still show signs of toxicosis if ivermectin is given in conjunction with P-glycoprotein inhibitors (Table 7). Recently, the FDA issued a safety warning stating that some dogs have developed signs of ivermectin toxicity when high extralabel doses of ivermectin are used concurrently with spinosad (Comfortis—Eli Lilly).23 Additional information can be found in the Lilly Companion Animal Health Technical Bulletin (http:/ /elms.xh1.lilly .com/10788_03_tech_Bulletin.pdf). Thus, dogs receiving ivermectin for the treatment of demodicosis should not receive concurrent treatment with spinosad. Milbemycin oxime—Oral milbemycin oxime (Interceptor—Novartis Animal Health) is recommended at a dose of 1.5 to 2 mg/kg/day, although dose ranges of 0.5 to 3.1 mg/kg/day have been used.10,24,25 Cure rates vary but are better with higher doses. Ivermectin-sensitive breeds generally tolerate milbemycin oxime at the doses outlined above.26 Side effects of daily milbemycin oxime administration are similar to those of ivermectin and include depression, stupor, coma, ataxia, and seizures. The major limitation of this drug is expense. We have treated demodectic otitis topically with a commercial solution containing 0.1% milbemycin oxime (MilbeMite Otic Solution—Novartis Animal Health); this use is considered extralabel. Moxidectin—Few studies are available, but moxidectin (Cydectin injectable—Fort 456 August 2008 VETERINARY MEDICINE

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Veterinary Medicine - August 2008 Contents Editors' Note Leading Off ClinQuiz Idea Exchange Practical Matters Diagnosing and Treating Canine Copper-Associated Hepatopathies Canine and Feline Demodicosis CE Form Advertiser Index Product Preview Marketplace/Classifieds Mind Over Miller

Veterinary Medicine - August 2008

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