Emodepside

The purpose of the study was to evaluate the proportional reporting of neurological adverse events (AEs) associated with feline topical parasiticide products containing macrocyclic lactones (MLs; including eprinomectin) and emodepside by use of postapproval pharmacovigilance data. The intent was to provide veterinarians prescribing these products for their feline patients with the overall comparative context of neurological AE reporting for these products, which have been characterized as substrates for P-glycoprotein transporters.

The openFDA and EudraVigilance Veterinary Data Warehouse databases were queried for neurological AEs cumulatively reported through December 31, 2024, for marketed parasiticide products containing MLs (eprinomectin, selamectin, moxidectin) and emodepside for topical administration to cats. The frequencies of neurological AE reporting were compared between products with proportional report rates and disproportionality statistical measures.

The reporting frequencies of neurological AEs associated with these feline topical parasiticide products were similar. For all products, ataxia was the most frequently reported neurological AE, with proportional report rates ranging from 5.3% to 14.0%. Proportional report rates ranged from 1.7% to 10.7% for convulsion and muscle tremor.

An evaluation of pharmacovigilance data from 2 different sources revealed no evidence of greater proportional reporting for neurological AEs specific to the use of eprinomectin-containing products in cats than for other MLs or emodepside.

These findings supported the conclusion that ML-containing products (including eprinomectin-containing products) and emodepside are comparable in the frequencies and types of neurological AEs associated with feline topical parasiticide products described as substrates for P-glycoprotein transporters.

The emergence and spread of anthelmintic resistance represent a major challenge for treating parasitic nematodes, threatening mass‐drug administration control programs in humans and zoonotic hosts. Currently, experimental evidence to understand the influence of management (e.g., treatment dose and frequency) and parasite‐associated factors (e.g., genetic variation, population size and mutation rates) is scarce. To rectify this knowledge gap, we performed controlled evolution experiments with the model nematode Caenorhabditis elegans and further evaluated the evolution dynamics with a computational model. Large population size was critical for rapid ivermectin resistance evolution in vitro and in silico. Male nematode production was favored during resistance evolution, suggesting a selective advantage of sexual recombination under drug pressure in vitro. Evolution of ivermectin resistance led to reduced efficacy of the structurally related anthelmintic moxidectin, as anticipated, as well as reduced efficacy of the structurally unrelated anthelmintic emodepside, which has a distinct mode of action. In contrast, albendazole, levamisole, and monepantel efficacy were not influenced by the evolution of ivermectin resistance. We conclude that combining computational modeling with in vitro evolution experiments to test specific aspects of evolution directly represents a promising approach to guide the development of novel treatment strategies to anticipate and mitigate resistance evolution in parasitic nematodes.