{"id":24127,"date":"2021-08-16T19:21:19","date_gmt":"2021-08-16T19:21:19","guid":{"rendered":"https:\/\/todaysveterinarypractice.com\/?p=24127"},"modified":"2022-04-08T14:16:13","modified_gmt":"2022-04-08T14:16:13","slug":"selamectin-use-in-companion-animals","status":"publish","type":"post","link":"https:\/\/navc.sitepreview.app\/todaysveterinarypractice.com\/pharmacology\/selamectin-use-in-companion-animals\/","title":{"rendered":"Selamectin Use in Companion Animals"},"content":{"rendered":"

Selamectin is an avermectin parasiticide with a variety of labeled uses in dogs and cats. It is unique in the avermectin class as it is applied topically and not administered orally. It was developed by Pfizer (now Zoetis<\/a>) and approved by the U.S. Food and Drug Administration (FDA) in 1999 with the trade names Revolution and Stronghold. The trade name varies by geographic region.1<\/sup><\/span><\/p>\n

The FDA approved abbreviated new animal drug applications (ANADAs) for Selarid (Norbrook, norbrook.com<\/a>) and Senergy (Virbac, virbac.com<\/a>), both of which are generic versions of selamectin.2<\/sup> Several other drug manufacturers have also submitted ANADAs for generic selamectin formulations.<\/p>\n

In November 2018, the FDA approved Revolution Plus (selamectin and sarolaner topical solution; Zoetis, <\/span>zoetis.com<\/span><\/a>) for use in cats. Revolution Plus is now the most comprehensive feline antiparasitic product on the market with the addition of sarolaner to provide efficacy against 3 different tick species.3<\/sup><\/span><\/p>\n

Mechanism of Action<\/h2>\n

Selamectin belongs to the macrocyclic lactone family, which comprises 2 groups: avermectins and milbemycins. Members of the avermectin group\u2014such as ivermectin, eprinomectin, and doramectin, as well as selamectin\u2014are structurally related. Avermectins bind to glutamate-gated chloride channels, which causes increased permeability of chloride to neurons and leads to hyperpolarization and ultimately parasite death. Mammals do not have glutamate-gated chloride channels and are thus spared the life-threatening effects of avermectin binding.\u00a0<\/span><\/span><\/p>\n

However, avermectins, including selamectin, do bind GABAA<\/sub> receptors present in the central nervous system of mammals. Normally, the intact blood\u2013brain barrier with functional P-glycoprotein (P-gp) protects the GABAA<\/sub> receptors. P-gp is a transmembrane efflux protein encoded by the ABCB1<\/i> (formerly MDR1<\/i>) gene and it is responsible for actively transporting various xenobiotics out of the central nervous system.4<\/sup> However, some dogs have a genetic defect (ABCB1-1\u2206<\/i>) that results in nonfunctional P-gp and increased risk for various adverse effects associated with excessive P-gp substrate drug concentrations in the central nervous system (<\/span>BOX 16<\/sup><\/span><\/strong>).5<\/sup> The Washington State University Veterinary Clinical Pharmacology Laboratory genotypes dogs via a blood sample or cheek swab; samples can be submitted via veterinarian, or owners may send samples to the laboratory directly (<\/span>vcpl.vetmed.wsu.edu<\/span><\/a>). Dogs that are homozygous for the ABCB1-1\u2206<\/i> mutation therefore cannot be treated with extra-label doses of ivermectin, as may be used for conditions such as demodectic mange. It is important to note that the labeled doses of FDA-approved heartworm prevention products are safe, even in homozygous mutant dogs.\u00a0<\/span><\/span><\/p>\n

Box 1 Breeds With Documented ABCB1-1\u2206 Mutation<\/div>
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