Trifexis has been demonstrated to be safe in healthy dogs when used according to label directions. Spinosad, one of its active ingredients, is produced by a bacterium first isolated from natural sources (a soil sample collected in the Caribbean).1 Spinosad selectively targets the nervous system of the flea (and other insects) due to differences in the targeted receptors compared to mammalian nervous systems.2 However, as with all medications, sensitivities due to individual animals can occur, sometimes resulting in side effects. See the Trifexis label for complete safety information.