Safety evaluation of lotilaner in dogs after oral administration as flavoured chewable tablets (Credelio™)

Abstract

BackgroundLotilaner (Credelio™, Elanco) is a novel isoxazoline that provides rapid speed of flea and tick knockdown which is sustained for at least 1 month following oral administration to dogs. The safety of lotilaner flavoured chewable tablets was investigated in a randomized, blinded, parallel-group design study in healthy Beagle puppies starting at 8 weeks of age. Lotilaner was administered orally once a month over 8 months at one, three and five times the upper level of the recommended dose range (of 20 to 43 mg/kg).MethodsThe objective of this study was to determine the safety of lotilaner flavoured chewable tablets in healthy dogs when administered monthly over an extended time period at the highest recommended dose rate, i.e. 1× and at elevated dose rates, i.e. 3× and 5×. Sixteen male and 16 female healthy 8-week-old puppies, weighing ~1.5 to 3.0 kg, were randomized among four groups to be untreated controls or to receive lotilaner at dose rates of 43 mg/kg (1×), 129 mg/kg (3×), or 215 mg/kg (5×) on eight occasions - every 4 weeks over 8 months. The control group was sham-dosed. Study dogs were fed within 30 min prior to treatment. Assessment of safety was based on general health observations, detailed clinical observations, complete physical/neurological examinations, including ophthalmological examinations and clinical pathology evaluations (haematology, clinical chemistry and urinalysis), food and water consumption, body weight, pharmacokinetic blood collections, macroscopic and microscopic examinations.ResultsBlood concentrations of lotilaner confirmed systemic exposure of all study dogs with the exception of the control group. Lotilaner did not induce any treatment-related effects on body weight, food consumption, opthalmoscopic, physical/neurological and electrocardiographic examinations. For clinical pathology, no changes related to treatment were noted. There were no treatment-related changes in gross examinations. After microscopic examinations, minor findings recorded in kidneys were of no toxicological relevance. Changes in the reproductive tissues were attributed to the peri-pubertal age and growth of the animals.ConclusionsLotilaner was well-tolerated in healthy puppies at 8 week of age when administered once monthly on eight occasion over 8 months at the highest recommended dose and at three and five-fold overdose.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2468-y) contains supplementary material, which is available to authorized users.

In-home assessment of flea control and dermatologic lesions in dogs provided by lotilaner (Credelio®) and spinosad (Comfortis®) in west central Florida

“…There was no reduction in efficacy observed in dogs that vomited at approximately two hours post treatment and were not re-dosed. For lotilaner, the study confirmed the safety that has been reported from early laboratory work demonstrating a wide safety margin, including in young puppies, and from field reports ( Cavalleri et al, 2017c , Karadzovska et al, 2017 , Kuntz and Kammanadiminti, 2017 ). The safety of lotilaner has been attributed to its exclusive selective binding to insect GABA-gated chloride channel receptors while not having the capacity to bind to mammalian receptors so that potent insecticidal potency is retained along with a wide safety margin ( Rufener et al, 2017 ).…”

Survey of canine use and safety of isoxazoline parasiticides

“…The earlier reports of these synthesized compounds and their mechanisms of action laid the groundwork for subsequent pre‐clinical studies as parasiticides, which were described in a special issue of Veterinary Parasitology in 2014 (Drag, Saik, Harriman, & Larsen, 2014; Shoop et al., 2014). Subsequent to their development as parasiticides they are now widely used throughout the world and are considered by most to be efficacious and safe, even in 8‐week old puppies (Drag et al., 2014; Kuntz & Kammanadiminti, 2017). However, despite the estimated millions of doses being given, adverse events (AE) that had previously been believed to be rare (Gaens, Rummel, Schmidt, Hamann, & Geyer, 2019; Quan et al., 1999), post‐marketing AE have been increasingly reported since the release of these products.…”

Clinical, Parasitological, and Serological Follow-Up of Dogs with Sarcoptic Mange Treated Orally with Lotilaner

“…All three molecules are registered in several countries for the treatment of sarcoptic mange in dogs. Lotilaner has previously been shown to be an effective and safe treatment against fleas and ticks [ 30 – 34 ] and is licensed solely for that purpose. However, it has already been demonstrated to possess broader potent acaricidal properties against mites such as Demodex canis [ 35 ].…”