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93 MAY/JUNE 2017 ■ TVPJOURNAL.COM PRACTICAL PARASITOLOGY ISOXAZOLINES These products selectively inhibit insect gamma- aminobutyric acid (GABA)- and glutamate-gated chloride channels. This induces hyperexcitation and uncontrolled central nervous system activity, resulting in death of the insect. 1 There are currently three agents in this category: afoxolaner, fluralaner, and sarolaner. Because the agents are very similar in many respects, they will be discussed together. Afoxolaner (NexGard; nexgardfordogs.com ), fluralaner (Bravecto; us.bravecto.com ), and sarolaner (Simparica; simparica.com ) are all available as flavored chewable oral tablets labeled for dogs only; fluralaner is also available in a topical formulation for both cats and dogs. 20–22 Afoxolaner and sarolaner are given monthly, whereas fluralaner is given every 3 months. 20–22 Because these tablets are flavored with food-based ingredients (soy or pork), they are not suitable for administration during food allergy elimination diet trials, and they may or may not be tolerated by food-allergic individuals. However, because of fluralaner's extended duration of action, it may be given at the beginning of an elimination diet, with efficacy expected to continue through the 10- to 12-week duration of the trial. Afoxolaner and sarolaner may be given with or without food, but the bioavailability of fluralaner is best when the agent is given with food. 20 All 3 agents have very good efficacy against adult fleas and may also have clinically significant inhibition of flea reproduction. They are also efficacious against many species of ticks, including Ixodes scapularis, Dermacentor variabilis, Rhipicephalus sanguineus, and Amblyomma americanum. 20–22 However, fluralaner must be given every 2 months for maximal efficacy against A americanum. 20 Sarolaner also has efficacy against A maculatum. 22 All of the agents appear to have very good efficacy against canine demodicosis. 23–25 Evidence shows that they are also effective against Sarcoptes, although whether this is reliable enough to permit diagnostic therapy remains to be seen. 26–28 Sarolaner has also been demonstrated to be efficacious against Otodectes species. 25 Overall, the 3 agents are well tolerated, with vomiting being the most common adverse effect. 20–22 Afoxolaner should be given with caution in animals with preexisting seizure disorders, as breakthrough seizures have been reported. 21 Seizures, ataxia, and trembling have been reported with sarolaner and with topical (but not oral) fluralaner in dogs. 20,22 Similar reactions have not been reported in cats with topical fluralaner. The oral formulations of all agents are expected to be waterproof. Topical fluralaner is expected to be very water resistant after 3 hours. 20 MISCELLANEOUS ACTIVE INGREDIENTS Selamectin This agent is an avermectin, similar to ivermectin. 1,29 It activates insect glutamate- gated chloride channels, which causes paralysis and eventual death of the fleas. It is marketed as a spot-on product for both cats and dogs. It is primarily used for its heartworm preventive and flea control properties but also has label claims against Otodectes, Dermacentor, and Sarcoptes species in dogs and Otodectes, Toxocara, and Ancylostoma species in cats. 29 It inhibits development of immature flea stages. 30 Unlike some other avermectins, selamectin can be administered to ivermectin-sensitive dogs (although salivation and ataxia have been reported with extralabel dose administration in these breeds). 29 Selamectin is systemically absorbed and is essentially waterproof after 2 hours. Fipronil This agent belongs to the phenylpyrazole class. 1 Like the isoxazolines, it acts by blocking GABA- and glutamate-gated chloride channels, causing hyperexcitation and death. It is available as both a spray and a spot-on. Fipronil is available in numerous formulations, many of which include other agents (such as permethrin or amitraz). It