Efficacy against nematode infections and safety of afoxolaner plus milbemycin oxime chewable tablets in domestic dogs under field conditions in Europe

Abstract

Afoxolaner (AFX) plus milbemycin oxime (MO) combination chewable tablets (NexGard Spectra®, Merial) were evaluated for safety and efficacy against naturally acquired nematode infections in domestic dogs in a multi-centre, positive control, blinded field study using a randomized block design based on the order of presentation for allocation. In total, 408 dogs confirmed positive for naturally acquired infections of intestinal nematodes by pre-treatment faecal examination were studied in ten countries in Europe (Albania, Austria, Bulgaria, France, Germany, Hungary, Italy, Lithuania, Romania and Slovakia). Pre-treatment faecal examination revealed Toxocara, Toxascaris, hookworm, Trichuris and/or Capillaria nematode infections in 134, 30, 223, 155 and 14 dogs, respectively. Dogs were allocated to one of two treatment groups in a ratio of 1, AFX + MO chewables (≥2.5 mg AFX + ≥0.5 mg MO per kg body weight, according to dose bands; 207 dogs), and 1, MO plus praziquantel (PRZ) chewables (Milbemax®, Novartis; ≥0.5 mg MO + ≥5 mg PRZ per kg body weight, according to the manufacturer's instructions; 201 dogs) and treated once. For evaluation of efficacy based on reduction of faecal nematode egg counts, two faecal samples, one collected prior to treatment and one collected 9 to 21 days after treatment, were examined using modified McMaster techniques. For evaluation of systemic safety, dogs were examined by a veterinarian before treatment administration and at study end, and dog owners observed the health status of their dogs until the end of the study and reported any abnormal observation. For dogs treated with AFX + MO chewables, the efficacy was 99.7, 99.7, 97.2, 99.7 and 99.7 % for Toxocara, Toxascaris, hookworm, Trichuris and Capillaria, respectively; and the efficacy was 99.5, 99.4, 94.3, 99.9 and 98.0 %, respectively, for the MO + PRZ-treated dogs (p ≤ 0.002 for all nematodes and both treatments). For Toxocara, hookworm and Trichuris, non-inferiority analysis demonstrated that the efficacy of AFX + MO chewable tablets was equal to or better than that of MO + PRZ. In spite that both treatments were ≥98 % efficacious against Toxascaris and Capillaria, a hypothesis of non-inferiority for both genera could not be established due to the low number of dogs infected with these parasites. No treatment-related adverse experiences were observed throughout the study. For both treatments, all dogs were given a systemic safety score of 'excellent' apart from one dog in each treatment group which received a score of 'acceptable'. AFX + MO combination chewables were shown to be safe and demonstrated a high level of efficacy when administered once to dogs infected with a broad range of parasitic nematodes under field conditions.

Field efficacy and safety of a novel oral chewable tablet containing sarolaner, moxidectin and pyrantel (Simparica Trio™) against naturally acquired gastrointestinal nematode infections in dogs presented as veterinary patients in Europe and the USA

“…The efficacy observed in the present field studies is comparable to the results from a recently reported European field study of similar design and methodology [10] in which geometric mean roundworm and hookworm fecal egg counts were reduced by ≥ 97.2% following a single oral dose of afoxolaner + milbemycin oxime, and by ≥ 94.3% following a single oral dose of milbemycin oxime + praziquantel (Milbemax ® ; Elanco, Greenfield, IN, USA). It was however unexpected that the combination of ivermectin + pyrantel in the present USA study only provided 74.7% efficacy against A. caninum.…”

Preventive efficacy of NexGard Spectra® against Dipylidium caninum infection in dogs using a natural flea (Ctenocephalides felis) infestation model

“…In addition to providing monthly flea and tick control and a deworming effect against roundworms, hookworms, whipworms, heartworm larvae and lungworm [12, 16, 17, 22], the regular monthly use of NexGard Spectra ® should indirectly help to prevent the infection of dogs by D. caninum .…”

“…NexGard Spectra ® is an oral chewable formulation containing afoxolaner, an insecticidal-acaricidal compound of the isoxazoline family, and milbemycin oxime, a nematodicidal compound [17]. It is intended to protect dogs against flea and tick infestation, and to deworm against gastro-intestinal nematodes as well as some other nematode infections ( Dirofilaria immitis , Angiostrongylus vasorum ) [9, 12, 16, 22]. Since milbemycin oxime is only nematodicidal, no efficacy is claimed against tapeworms.…”

Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight‐week‐old dogs

“…In combination, the minimum therapeutic dose of afoxolaner for monthly efficacy against fleas and ticks is 2.5 mg/kg, and the minimum therapeutic dose of milbemycin oxime against adult intestinal nematode infections, and to prevent heartworm disease by interrupting the life cycle of Dirofilaria immitis, is 0.5 mg/kg (Hamel et al, 2015;Knaus et al, 2015;Kondo et al, 2015;Rehbein et al, 2015a andRehbein et al, 2015b;Tielemans et al, 2015). The calculation of the maximum exposure dose is dependent on the weight ranges developed for the commercial presentations.…”