Abstract
<jats:sec> <jats:title>Background</jats:title> <jats:p> Fluralaner is an isoxazoline widely used for flea and tick control in dogs, mainly in long-acting formulations. However, the performance of short-acting, lower-dose options remains unexplored in scientific literature. This study evaluated the efficacy of a short-acting oral fluralaner formulation (WellPet™–Ourofino Saúde Animal Ltda, São Paulo, Brazil; 10–22.5 mg of fluralaner per kg of body weight) against <jats:italic>Ctenocephalides felis felis</jats:italic> and <jats:italic>Rhipicephalus sanguineus</jats:italic> sensu lato under controlled and field conditions in southeastern Brazil. </jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A randomized, blinded, negative-controlled laboratory study assessed intrinsic efficacy using standardized artificial infestations over 49 days. A randomized, assessor-blinded positive-controlled field trial compared fluralaner with sarolaner in naturally infested dogs living in private households. Fleas and ticks were counted following WAAVP guidelines. Efficacy was calculated using arithmetic means, and statistical analyses were performed with Mann–Whitney and Wilcoxon tests. All analyses were conducted using IBM SPSS Statistics 31.0.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> In the controlled study, fluralaner produced a rapid reduction in parasite burdens, achieving 100% efficacy for fleas and ticks as early as Day +2. Efficacy remained between 98.3 and 100% for ticks and 99.7 and 100% for fleas throughout the entire period of evaluation. In the field trial ( <jats:italic>n</jats:italic> = 159), both fluralaner and sarolaner markedly reduced parasite loads from Day +7 onward. Efficacy remained above 97% for both parasites in both groups, with no significant differences between treatments at any time point. No product-related adverse events were observed, and the product remained effective even in a region dominated by the tropical lineage of <jats:italic>R. sanguineus</jats:italic> s.l., recently redescribed as <jats:italic>Rhipicephalus linnaei</jats:italic> . </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion</jats:title> <jats:p>This novel short-acting oral fluralaner formulation demonstrated rapid onset and sustained efficacy under experimental and real-world conditions, supporting its use as an effective option for flea and tick control in areas with high parasite pressure, with an unique periodicity of readministrations every 49 days.</jats:p> </jats:sec>