Target animal safety evaluation of a novel topical combination of esafoxolaner, eprinomectin and praziquantel for cats

• Published in: Parasite (Paris) 2021, Vol.28, p.18
• Main Authors: Gupta, Aradhana, Baker, Christine, Wang, Hailun, Targa, Norba, Pfefferkorn, Anthony, Tielemans, Eric
• Format: Article
• Language: English
• Subjects: Administration, Topical; Animals; Autopsies; cat; Cat Diseases - drug therapy; Cats; Combo (esafoxolaner, eprinomectin, praziquantel): A new endectocide spot-on formulation for cats. Invited Editor: Frédéric Beugnet; Dosage; Drug dosages; eprinomectin; esafoxolaner; Evaluation; Female; Ingestion; Intervals; Ivermectin - adverse effects; Ivermectin - analogs & derivatives; Juveniles; Necropsy; Parasites; Physical examinations; Praziquantel; Praziquantel - adverse effects; Product safety; Random Allocation; Safety; Special Issue – NexGard; topical; Veterinary medicine
• ISSN: 1776-1042; 1252-607X; 1776-1042
• DOI: 10.1051/parasite/2021015

The safety profile of NexGard Combo, a novel topical product for cats combining esafoxolaner, eprinomectin and praziquantel, for the treatment and prevention of internal and external parasites, was evaluated in kittens, in two margin-of-safety studies (Studies #1 and #2), and in an oral tolerance study (Study #3). In the margin of safety studies, kittens were dosed several times topically with multiples of the maximum exposure dose (1×): in Study #1, 3× and 5× doses four times at 2-week intervals; in Study #2, 1×, 3× and 5× doses six times at 4-week intervals. In Study #3, kittens were dosed orally once with a 1× dose. Furthermore, in Study #1, another group of kittens was dosed topically twice at a 4-week interval with a formulation of esafoxolaner as the sole active ingredient dosed at 23×. Physical examinations and clinical pathology analyses were performed throughout the studies, followed by necropsy and detailed histopathological evaluation in Studies #1 and #2. No significant treatment related effects were observed in the three studies, except for one occurrence of reversible neurological signs attributed to eprinomectin in one cat after the third 5× dose in Study #2, with clinical signs observed nine hours after dosing, pronounced for a few hours, significantly improved the next day, and absent 2 days after dosing. In conclusion, NexGard Combo was demonstrated safe in kittens following repeated topical administrations and following oral ingestion, and very high topical doses of esafoxolaner were well tolerated.