Kathryn Rook, VMD DACVD Clinical Assistant Professor of Dermatology University of Pennsylvania, School of Veterinary Medicine.

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1 Kathryn Rook, VMD DACVD Clinical Assistant Professor of Dermatology University of Pennsylvania, School of Veterinary Medicine July 27, 2017

2 Ecto- and endo- parasites are an important part of veterinary clinical medicine Identification of ectoparasitic infections continues to be a significant portion of daily practice in veterinary dermatology Most domestic animals are predisposed to development of ectoparasitic infections Sarcoptiform mites Demodex mites Psoroptiform mites Many others

3 Demodex injai Demodex canis Demodex cornei

4 One of the most common dermatologic diseases in dogs Prevalence in North America: 0.38%-0.58% Mexico: 23% Korea: 5% India: 3%

5 Only one FDA-approved treatment Amitraz Monoamine oxidase inhibitor (MAOI) Alpha-2 adrenergic properties Inhibits prostaglandin synthesis Leads to over-excitationàparalysisàdeath in insects Available only as a topical treatment High risk for adverse effects: sedation, bradycardia, vomiting, ataxia, vomiting, diarrhea, hyperglycemia

6 Macrocyclic lactones Ivermectin Most common off-label treatment for many years Daily oral therapy required for ~3-9 months Others: Milbemycin (oral) Moxidectin (oral and topical) Doramectin (injectable)

7 Toxicity can occur Easy to overdose ABCB1-1 (formerly MDR1) mutation Encodes for P-glycoprotein transmembrane protein pump Mutation common in herding breed dogs and their crosses Signs of toxicity: mydriasis, ataxia, sedation, stupor, coma, hypersalivation, vomiting, diarrhea, blindness, tremors, seizures, respiratory depression

8 Newest class of parasiticide discovered in early 2000s Isoxazolines GABA receptor antagonists Bind to chloride channels in nerves and musclesàblocks transmission of neuronal signalsàparalysisàdeath of insects Considered very safe with minimal side effects Vomiting immediately after administration is most common

9 Licensed in the USA as flea and tick preventatives for dogs and some for cats afoxolaner Monthly oral tablet (dogs only) fluralaner Every 3 month oral tablet (dogs only) Every 3 month topical applicator (cats, soon to be available for dogs) sarolaner Monthly oral tablet (dogs only)

10 Efficacy of oral afoxolaner for the treatment of canine generalised demodicosis Frédéric Beugnet 1,*, Lénaïg Halos 1, Diane Larsen 1, and Christa de Vos 2 1 Merial S.A.S., 29 avenue Tony Garnier, Lyon, France 2 Clinvet International (Pty) Ltd, PO Box 11186, 9321 Universitas, South Africa Efficacy of orally administered fluralaner (Bravecto TM ) or topically applied imidacloprid/ moxidectin (Advocate ) against generalized demodicosis in dogs Josephus J Fourie 1*, Julian E Liebenberg 1, Ivan G Horak 2, Janina Taenzler 3, Anja R Heckeroth 3 and Regis Frénais 4 Efficacy of sarolaner, a novel oral isoxazoline, against two common mite infestations in dogs: Demodex spp. and Otodectes cynotis Robert H. Six a,, Csilla Becskei b, Mark M. Mazaleski a, Josephus J. Fourie c, Sean P. Mahabir a, Melanie R. Myers a, Nathalie Slootmans b a Zoetis, Veterinary Medicine Research and Development, 333 Portage St., Kalamazoo, MI 49007, USA b Zoetis, Veterinary Medicine Research and Development, Mercuriusstraat 20, Zaventem B-1930, Belgium c ClinVet International (pty) Ltd., Uitsigweg, Bainsvlei 9338, Bloemfontein, South Africa

11 Demodex gatoi Demodex cati

12 va.com The use of oral fluralaner for the treatment of feline generalised demodicosis: a case report I. Matricoti *,1 and E. Maina * Servizi Dermatologici Veterinari, Bologna, 40125, Italy Servizi Dermatologici Veterinari, Lovere, 24065, Italy 1 Corresponding author irina.matricoti@gmail.com Fluralaner shown to be effective for D. cati Anecdotally effective for D. gatoi All isoxazolines effective against Otodectes Fluralaner also shown to be effective against Psoroptes mites in rabbits and Lynxacarus mites in cats

13 Vet Dermatol 2017 Afoxolaner and fluralaner treatment do not impact on cutaneous Demodex populations of healthy dogs Christine M. Zewe*, Laura Altet, Andrea T. H. Lam* and Lluıs Ferrer* DOI: /vde healthy dogs with no history of skin disease 10 each received afoxolaner or fluralaner RT-PCR performed for demodex DNA from hair plucks at d0, d30, d90 D0-5/20 positive; D30 3/18 positive; D90 6/20 positive Treatment with isoxazolines does not impact normal demodex populations

14 Demodicosis is a common disease in canine patients Severe infections secondary bacterial skin infections can occur Until recently, treatment involved daily administration of oral ivermectin This required months of treatment and significant risk for side effects Treatment of demodicosis (and other parasitic infestations) has been revolutionized by the discovery of the isoxazoline parasiticides. Decrease in frequency of administration of medications and quicker resolution of disease have improved both patient and owner quality of life

15 Beugnet F, Halos L, et al. Efficacy of oral afoxolaner for the treatment of canine generalized demodicosis. Parasite (2016) 23:14. Beugnet F, de Vos C, et al. Efficacy of afoxolaner in a clinical field study in dogs naturally infested with Sarcoptes scabiei. Parasite (2016) 23:26. Carithers D, Crawford J, et al. Assessment of afoxolaner efficacy against Otodectes cynotis infestation of dogs. Parasites & Vectors. (2016) 9:635. Fourie JJ, Liebenberg JE, et al. Efficacy of orally administered fluralaner (Bravecto ) or topically applied imidacloprid/moxidectin (Advocate ) against generalized demodicosis in dogs. Parasites & Vectors. (2015) 8:187. Gassel M, Wolf C, et al. The novel isoxazoline ectoparasiticide fluralaner: Selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity. Insect Biochemistry and Molecular Biology (2014) 45:111. Han HS, Noli C, et al. Efficacy and duration of action of oral fluralaner and spot-on moxidectin/imidacloprid in cats infested with Lynxacarus rodovskyi. Veterinary Dermatology (2016) 27:474. Kilp S, Ramirez D, et al. Comparative pharmacokinetics of fluralaner in dogs and cats following single topical or intravenous administration. Parasites & Vectors. (2016) 9:296. Matricoti I and Maina E. The use of oral fluralaner for the treatment of feline generalized demodicosis: a case report. Journal of Small Animal Practice. (2017) Early View. Ordeix L, Bardagi M, et al. Demodex injai infestation and dorsal greasy skin and hair in eight wirehaired fox terrier dogs. Veterinary Dermatology. (2009) 20:267. Ozoe Y, Asahi M, et al. The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels. Biochemical and Biophysical Research Communications. (2010) 391:744. Plant JD, Lund EM, et al. A case -control study of the risk factors for canine juvenile-onset generalized demodicosis in the USA. Veterinary Dermatology. (2010) 22:95. Romero C, Heredia R, et al. Efficacy of flurlaner in 17 dogs with sarcoptic mange. Veterinary Dermatology (2016) 27:353. Sheinberg G, Romero C, et al. Use of oral fluralaner for the treatment of Psoroptes cuniculi in 15 naturally infested rabbits. Veterinary Dermatology. (2017) Early View. Shoop WL, Hartline EJ, et al. Discovery and mode of action of afoxolaner, a new isoxazoline parasiticide for dogs. Veterinary Parasitology. (2014) 201:179. Six RH, Becskei C, et al. Efficacy of sarolaner, a novel oral isoxazoline, against two common mite infestations in dogs: Demodex spp. and Otodectes cynotis.veterinary Parasitology. (2016) 222:62. Taenzler J, Liebenberg J. et al. Efficacy of fluralaner administered either orally or topically for the treatment of naturally acquired Sarcoptes scabiei var. canis infestation in dogs. Parasites & Vectors. (2016) 9:392. Taenzler J, de Vos C, et al. Efficacy of fluralaner against Otodectes cynotis infestations in dogs and cats. Parasites & Vectors. (2017) 10:30 Zewe CM, Altet L, et al. Afoxolaner and fluralaner treatment do not impact on cutaneous Demodex populations of healthy dogs. Veterinary Dermatology. (2017) Early view.

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