Preventive efficacy of oral moxidectin at various doses and dosage regimens against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs

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Background: Infection with Angiostrongylus vasorum may cause severe clinical disease, even death in dogs, however, due to the often non-specific clinical signs, diagnosis is not always straightforward. Regular prophylactic treatment may offer a safe means to protect dogs against infection. The efficacy of a novel oral endectocide containing moxidectin, sarolaner and pyrantel was investigated for the prevention of angiostrongylosis in dogs in three placebocontrolled, randomized, masked studies. The initial study (Study 1) determined the efficacious dosage of moxidectin in the combination product by evaluating three different dose levels, and two follow-up studies (Studies 2 and 3) confirmed the efficacy of the selected moxidectin dose. Methods: Animals were infected orally with 200 infective third-stage larvae (L3) of A. vasorum and were treated 28 days later with the combination product or with placebo. Timing of dosing relative to infection allowed for efficacy to be evaluated against the immature adult (L5) stage. Dogs in Study 1 received treatments with oral tablets to deliver 3, 12 or 24 µg/kg moxidectin in combination with 2 mg/kg sarolaner and 5.0 mg/kg pyrantel (as pamoate salt) or placebo. In Studies 2 and 3, Simparica Trio ™ tablets were administered to provide minimum dosages of 1.2 mg/kg sarolaner, 24 µg/kg moxidectin and 5.0 mg/kg pyrantel (as pamoate salt). Efficacy of the combination product was calculated as the percent reduction in adult worm counts at necropsy relative to placebo. Results: In Study 1, the 3, 12 and 24 µg/kg moxidectin dosage in the combination product provided 7.2%, 54.5% and 94.7% efficacy against the immature adult stages of A. vasorum, respectively. Studies 2 and 3 confirmed that the efficacy of 24 µg/kg moxidectin combined with 1.2 mg/kg sarolaner and 5 mg/kg pyrantel in Simparica Trio ™ was ≥ 92.9%. All three studies established that a single oral administration of 24 µg/kg moxidectin in the combination product provided effective prophylactic treatment for angiostrongylosis, reduced L1 production and fecal excretion and minimized the tissue damage to the lungs. Conclusions: A single oral treatment of dogs with Simparica Trio ™ providing moxidectin at a minimum dose of 24 µg/kg was efficacious in the prevention of angiostrongylosis.

Section: Discussionmentioning

confidence: 99%

Efficacy of orally administered combination of moxidectin, sarolaner and pyrantel (Simparica Trio™) for the prevention of experimental Angiostrongylus vasorum infection in dogs

Becskei

Thys

Doherty³

et al. 2020

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“…The macrocyclic lactone (ML) class of anthelmintics are the only drug class widely available as heartworm preventatives and are highly effective in the prevention of canine heartworm disease [4]. These drugs work, likely in concert with the dog's immune system, by killing the immature third (L 3 ) and fourth (L 4 ) larval stages of D. immitis thus preventing development to adult worms [5].…”

Section: Introductionmentioning

confidence: 99%

“…These drugs work, likely in concert with the dog's immune system, by killing the immature third (L 3 ) and fourth (L 4 ) larval stages of D. immitis thus preventing development to adult worms [5]. Lack of efficacy (LOE) of ML heartworm preventatives can result from failure to regularly administer the product according to the approved label directions [4]; however, lack of efficacy due to D. immitis strains resistant to MLs is a growing concern [4].…”

Section: Introductionmentioning

confidence: 99%

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Preventive efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of Heartgard® Plus or Interceptor® Plus against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs

Kryda

Holzmer

Everett³

et al. 2020

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Background: Recent reports indicated that increasing the monthly oral dosage and the number of consecutive monthly doses of moxidectin improved the efficacy against macrocyclic lactone (ML)-resistant Dirofilaria immitis. The two laboratory studies reported here evaluated the efficacy of four or six monthly oral doses of 24 µg/kg moxidectin compared to six monthly doses of either Heartgard ® Plus (ivermectin/pyrantel) or Interceptor ® Plus (milbemycin oxime/praziquantel) against ML-resistant D. immitis strains. Methods: Dogs were inoculated 30 days prior to first treatment with 50 third-stage (L 3) larvae of a ML-resistant strain of D. immitis, ZoeLA or JYD-34. In each study, dogs (six per group) were randomized to treatment with six monthly doses of placebo, four or six monthly doses of 24 µg/kg moxidectin, or six monthly doses of Heartgard ® Plus or Interceptor ® Plus at their label dose rates. Efficacy was evaluated by adult heartworm counts approximately nine months after L 3 inoculation. Results: All negative-control dogs were infected with adult heartworms (geometric mean, 35.6; range, 24-41) for ZoeLA and (geometric mean, 32.9; range, 30-37) for JYD-34. Efficacies against ZoeLA for moxidectin, Heartgard ® Plus and Interceptor ® Plus were ≥ 96.1%, 18.7% and 21.2%, respectively. Adult counts for both moxidectin-treated groups were significantly lower than negative control (P < 0.0001), significantly lower than Heartgard ® Plus and Interceptor ® Plus (P < 0.0001), but not significantly different from each other (P = 0.5876). Counts for Heartgard ® Plus and Interceptor ® Plus were not significantly different than negative control (P ≥ 0.2471). Efficacies against JYD-34 were ≥ 95.9%, 63.9% and 54.6% for moxidectin, Heartgard ® Plus and Interceptor ® Plus, respectively. Counts for all groups were significantly lower than negative control (P ≤ 0.0001). Counts for six monthly doses of moxidectin were significantly

“…The isoxazoline class of ectoparasiticides such as sarolaner, afoxolaner, fluralaner and lotilaner are highly efficacious and have broader spectrum activity against ticks, fleas and/or mites [1][2][3][4][5][6][7][8][9]. The combination of the isoxazolines with one or more additional active ingredients has provided activity against other parasites, such as heartworm and gastrointestinal nematodes [10][11][12][13][14]. Heartworm disease caused by Dirofilaria immitis is endemic in Australia [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of combination products containing sarolaner, moxidectin and pyrantel (Simparica Trio™) or afoxolaner and milbemycin (NexGard Spectra®) against induced infestations of Ixodes holocyclus in dogs

Packianathan¹,

Hodge²,

Bruellke³

et al. 2020

Background: The Australian paralysis tick, Ixodes holocyclus, causes tick paralysis in dogs and cats in the eastern coastal regions of Australia. Prevention is the best option to protect dogs against this potentially fatal disease and sarolaner provides rapid and sustained efficacy against I. holocyclus. In this laboratory study, the efficacy of two combination endectocides containing sarolaner + moxidectin + pyrantel (Simparica Trio ™) and afoxolaner + milbemycin (NexGard Spectra ®) was evaluated against an artificial infestation of I. holocyclus. Methods: Twenty-four (n =24) foxhounds were randomly allocated to three treatment groups and artificially infested with 30 adult female viable ticks on Days − 1, 7, 14, 21, 28 and 35. On Day 0, dogs in each treatment group were treated with either Drontal ® (control group), Simparica Trio ™ at the label dose to provide minimum doses of sarolaner (1.2 mg/kg), moxidectin (24 µg/kg) and pyrantel (5 mg/kg) or NexGard Spectra ® to provide minimum doses of afoxolaner (2.5 mg/kg) and milbemycin (0.5 mg/kg). Live tick counts were performed at 48 and 72 hours after treatment and after each re-infestation on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for control dogs based on geometric means. Results: Against an existing infestation, efficacy of both Simparica Trio ™ and NexGard Spectra ® was 99.6% and 100% at 48 and 72 h time points, respectively (P = 1.000). Against subsequent weekly infestations, treatment with Simparica Trio ™ and NexGard Spectra ® resulted in efficacy of ≥ 97.7% and ≥ 95.5% (P ≥ 0.0911), respectively at the 48 h time point and at the 72 h time point, Simparica Trio ™ and NexGard Spectra ® resulted in efficacy of ≥ 99.0% and ≥ 98.4% (P ≥ 0.0511), respectively. There were no treatment-related adverse events in the study. Conclusions: Single doses of Simparica Trio ™ and NexGard Spectra ® were highly efficacious and provided comparable efficacy against the Australian paralysis tick, I. holocyclus for up to 35 days.