afoxolaner and moxidectin

Infestation with Sarcoptes scabiei in dogs is a debilitating disease if left untreated and is transmissible to humans. Two field studies were conducted to confirm the efficacy of orally administered sarolaner in combination with moxidectin and pyrantel (Simparica Trio. Client-owned dogs with S. scabiei infestation were enrolled and received 2 monthly treatments. In the first, small-scale study, 12 dogs each were allocated randomly to treatment with either placebo or Simparica Trio. In the small-scale study, 2 monthly doses of Simparica Trio. Two-monthly doses of Simparica Trio

Topics: Acaricides; Animals; Dog Diseases; Dogs; Humans; Mite Infestations; Pyrantel; Sarcoptes scabiei; Scabies; Tablets; Treatment Outcome

One randomized, controlled clinical field study was conducted in 18 general veterinary practices throughout the USA to evaluate the safety and efficacy of a novel oral chewable combination tablet, Simparica Trio™, containing sarolaner, moxidectin and pyrantel for the treatment and prevention of fleas on dogs.. Client-owned dogs, from households of three or fewer dogs were eligible for enrollment. Four hundred and twenty-two dogs from 251 households were enrolled. Households were randomly assigned in a 2:1 ratio to treatment with either Simparica Trio™ at the minimum label dose of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5 mg/kg pyrantel (as pamoate salt) or afoxolaner (NexGard. Simparica Trio™ reduced geometric mean live flea counts by 99.0% by Day 30 and by 99.7% by Day 60. As a result of the rapid reduction in flea infestations, clinical signs associated with FAD substantially improved following treatment. Simparica Trio™ was well-tolerated and a diverse range of concomitant medications were administered to dogs during the course of the study. Simparica Trio™ chewable tablets were well-accepted by dogs, with the majority of flavored chewable tablets (91.9%) voluntarily consumed by free choice without, or when offered in food.. Simparica Trio™ administered orally once monthly for two consecutive treatments was safe and effective against natural flea infestations and substantially improved clinical signs associated with FAD in client-owned dogs in a field study conducted in the USA.

Topics: Acaricides; Administration, Oral; Animals; Azetidines; Dermatitis; Dog Diseases; Dogs; Drug Combinations; Female; Flea Infestations; Hospitals, Animal; Isoxazoles; Macrolides; Male; Naphthalenes; Parasite Load; Pyrantel; Siphonaptera; Spiro Compounds; Tablets; Treatment Outcome; United States

Zoonotic visceral leishmaniasis (ZVL) caused by Leishmania (Leishmania) infantum is an important disease in humans and dogs. Different mammal species are reservoirs but dogs are considered to be the main one. Phlebotomine sand flies are the proven vector. Four systemic insecticides approved for their use in dogs were previously selected based on their potential to be used in endemic countries as part of the control programs of ZVL. These insecticides are proved to be safe and effective against the on-label insects and parasites, but there is no information about their activity against phlebotomine sand flies.. The phlebotomine mortality of four systemic insecticides in dogs was evaluated using two randomized clinical trials. For the first trial, thirty dogs were randomly allocated into five groups: four treatments and one control, of equal size. The treatments evaluated were: Guardian®SR, Elanco (moxidectin); Comfortis®, Elanco (spinosad); Bravecto®, Merck Animal Health (fluralaner); and NexGard®, Merial (afoxolaner). Blood from dogs was taken at days 2, 4, 21 and 31 post-treatment (trial 1). The compound that showed the highest efficacy was selected for a second trial (trial 2) with 20 dogs sampled at days 0, 2, 4, 7, 14, 18, 32, 39, 51 and 84 post-treatment. Membrane feeding bioassays with Phlebotomus papatasi were used to evaluate the phlebotomine mortality efficacy of the different treatments. Phlebotomine mortality was observed every 24 h following the membrane feeding during 5 days. A mixed model for a negative binomial logistic regression, and a Cox proportional hazard mixed model were used to estimate phlebotomine mortality due to different treatments.. Fluralaner was the only compound that showed significant phlebotomine mortality. Fluralaner maintained the phlebotomine mortality between 60-80% for 30 days after treatment. In trial 1 we found that fluralaner increased the risk of death by 1.9 times (95% CI: 1.02-3.6) and 1.7 times (95% CI: 1.09-2.6) at days 2 and 4 after treatment. The Cox model resulted in an increase of 1.47 (95% CI: 1.1-1.96) times in hazard risk at day 2 and 1.89 (95% CI: 1.35-2.45) at day 4 after treatment. In trial 2 we found that fluralaner increased the risk of death by 1.64 times (95% CI: 1.16-2.54) and 1.97 times (95% CI: 1.23-3.17) at days 14 and 32. The hazard risk was also increased by 1.92 (95% CI: 1.4-2.64) times at day 14 after treatment. Phlebotomine survival including all experimental days was significantly lower in the fluralaner group in both trials.. A single oral treatment of fluralaner in dogs induces phlebotomine mortality. Systemic insecticides in dogs should be considered as a potential preventive measure of ZVL.

Topics: Absorption, Physiological; Animals; Disease Vectors; Dog Diseases; Dogs; Drug Combinations; Female; Insecticides; Isoxazoles; Leishmania infantum; Leishmaniasis, Visceral; Macrolides; Male; Naphthalenes; Phlebotomus

Safety and efficacy of the combined monthly use of spot-on fipronil 6.76% w/v / permethrin 50.48% w/v (Frontline Tri-Act®) and chewable tablets of afoxolaner 1.9% w/w / milbemycin oxime 0.4% w/w (NexGard Spectra®) in dogs was evaluated in a field study over a period of 6 months.. Forty-one healthy dogs living in highly endemic area for canine leishmaniosis and other canine vector borne diseases (VBD) were included in the study at the beginning of the Leishmania transmission season. Sixteen dogs were pet dogs living each in a single household; twenty-five dogs were hunting dogs living in three kennels. At inclusion, the dogs were ELISA (rapid test) negative for antibodies to Anaplasma, Borrelia, Ehrlichia, and for antigens of Dirofilaria. The dogs were also negative for blood microfilariae at the Knott's test, and no clinical or haematological abnormalities were observed. Of the included dogs, six hunting, apparently healthy, dogs were ELISA (rapid test) positive to Leishmania, and some were naturally infected by gastrointestinal nematodes (58.5%) and/or infested by fleas (58.5%) and ticks (9.8%). All the included dogs were treated at Days 0, 28, 56, 84, 112 and 140, and followed-up for efficacy until the study end (Day 168).. No adverse events related to the two products, nor skin reactions, general signs, or changes in the haematological profile, were observed during the study. At Day 14, anthelminthic efficacy was 100% for Toxocara canis, Toxascaris leonina and Capillaria aerophila, while few hunting dogs were still shedding eggs of Trichuris vulpis (1/25 hunting dog) and Ancylostomatidae (9/25 hunting dogs). All pet dogs were nematode free at the end of the study. Hunting dogs were free of roundworms and whipworms. Twenty-four hours after the first treatment, 95.8% of the ectoparasite infested dogs were free from fleas and ticks. Ectoparasites were significantly controlled during the 6-month study period, with 100% efficacy on both fleas and ticks from Day 56 to Day 168. Blood and serum samples collected on Day 168 were tested for vector-borne pathogens using same methods of the inclusion and no new seroconversions or circulating blood microfilariae were observed.. Concomitant use of Frontline Tri-Act® and NexGard Spectra® in dogs for six months was well tolerated. The combination was effective in controlling fleas, ticks, gastro-intestinal nematodes, and neither new seroconversion to the tested vector-borne pathogens nor blood microfilariae were detected in treated dogs at the end of the study.

Topics: Animals; Dog Diseases; Dogs; Drug Combinations; Female; Insect Vectors; Insecticides; Isoxazoles; Macrolides; Male; Naphthalenes; Parasitic Diseases, Animal; Permethrin; Pyrazoles

The efficacy of oral treatment with a chewable tablet containing afoxolaner 2.27% w/w (NexGard(®), Merial) administered orally was assessed in eight dogs diagnosed with generalised demodicosis and compared with efficacy in eight dogs under treatment with a topical combination of imidacloprid/moxidectin (Advocate(®), Bayer). Afoxolaner was administered at the recommended dose (at least 2.5 mg/kg) on Days 0, 14, 28 and 56. The topical combination of imidacloprid/moxidectin was given at the same intervals at the recommended concentration. Clinical examinations and deep skin scrapings were performed every month in order to evaluate the effect on mite numbers and the resolution of clinical signs. The percentage reductions of mite counts were 99.2%, 99.9% and 100% on Days 28, 56 and 84, respectively, in the afoxolaner-treated group, compared to 89.8%, 85.2% and 86.6% on Days 28, 56 and 84 in the imidacloprid/moxidectin-treated group. Skin condition of the dogs also improved significantly from Day 28 to Day 84 in the afoxolaner-treated group. Mite reductions were significantly higher on Days 28, 56 and 84 in the afoxolaner-treated group compared to the imidacloprid/moxidectin-treated group. The results of this study demonstrated that afoxolaner, given orally, was effective in treating dogs with generalised demodicosis within a two-month period.

Topics: Acaricides; Administration, Oral; Animals; Dog Diseases; Dogs; Female; Follow-Up Studies; Imidazoles; Isoxazoles; Macrolides; Male; Mite Infestations; Naphthalenes; Neonicotinoids; Nitro Compounds; Skin; Tablets; Time Factors

Dirofilaria immitis, the mosquito-borne agent of dirofilariosis, a chronic and sometimes fatal cardiopulmonary canine disease, is endemic in most warm and temperate regions in the world. The efficacy of an oral endectoparasiticide product (test product or TP) combining moxidectin, afoxolaner, and pyrantel pamoate was evaluated for the prevention of heartworm disease in dogs, in two laboratory and one field studies. In each laboratory study, 20 D. immitis-naïve beagle dogs were experimentally infected with D. immitis. Ten control dogs were sham-treated, and ten dogs were administered the TP targeting the minimum effective dose, six times monthly and starting 30 days post infection. At necropsy seven months after inoculations, no heartworms were found in any of the TP treated dog, whereas 19 to 42 live heartworms were found in the control dogs. In each study, treatment efficacy was 100% and the difference between treated and untreated groups was highly significant (p < 0.0001). A field study was conducted through the full transmission season in several heartworm-endemic regions of the United States. One hundred and twenty client-owned dogs that were negative for D. immitis at enrollment were administered twelve monthly oral doses of the TP at label dose. Blood tests for D. immitis antigen and modified Knott's tests for microfilariae remained negative through the full duration of the study, demonstrating that all dogs were protected from heartworm infection during the full transmission season. These studies demonstrated that TP administered monthly for at least six doses is effective at preventing dirofilariosis.

Topics: Animals; Dirofilaria immitis; Dirofilariasis; Dog Diseases; Dogs; Heart Diseases; Macrolides; Pyrantel Pamoate; United States