Efficacy of fluralaner plus moxidectin (Bravecto® Plus spot-on solution for cats) against Otodectes cynotis infestations in cats.

BACKGROUND: The efficacy of the fixed combination of fluralaner plus moxidectin for the treatment of Otodectes cynotis infestations was evaluated in cats after topical application. METHODS: Sixteen cats experimentally infested with O. cynotis were allocated randomly to two groups of 8 cats each. One group was treated topically with the fixed combination of fluralaner plus moxidectin at the minimum dose rate of 40 mg fluralaner and 2 mg moxidectin/kg body weight. The other group was treated with physiological saline solution. Before and 14 and 28 days after treatment the ears of all cats were examined otoscopically for live mites and for the amount of debris and cerumen. Twenty-eight days after treatment, the cats were sedated and had both ears flushed to obtain the total number of live mites per animal. Efficacy was calculated, based on the results of the ear flushing, by comparing mean live mite counts in the fluralaner plus moxidectin treated group versus the saline group. RESULTS: A single topical application of the fixed combination of fluralaner plus moxidectin to cats reduced the mean mite counts by 100% (P < 0.001) by 28 days after treatment. No mites were visible during otoscopic examination at either 14 or 28 days after treatment. All fluralaner plus moxidectin treated cats had less ceruminous exudate 28 days after treatment compared to pre-treatment and 14 days after treatment. No treatment related adverse events were observed in any cats enrolled in the study. CONCLUSIONS: Single topical application of the fixed combination of fluralaner plus moxidectin was highly effective against O. cynotis infestations in cats.

Efficacy of fluralaner (Bravecto™ chewable tablets) for the treatment of naturally acquired Linognathus setosus infestations on dogs.

BACKGROUND: The clinical efficacy of fluralaner chewable tablets (Bravecto™, MSD Animal Health) against naturally acquired Linognathus setosus infestations on dogs was evaluated compared with permethrin (Exspot®, MSD Animal Health) treatment. METHODS: Privately-owned dogs naturally infested with L. setosus from 21 different households were randomly allocated to two treatment groups. Fourteen dogs were treated once orally with fluralaner and ten dogs were treated once topically with permethrin, at the recommended label dose. Live L. setosus on all dogs were counted before treatment and 1, 7, 28 (both groups) and 84 (fluralaner group) days post-treatment according to a coat parting technique at pre-specified locations and lice species were confirmed microscopically. At the same time points, a veterinary dermatology severity score and an owner's perceived pruritus score were recorded. RESULTS: Percentage reduction in geometric mean L. setosus counts, comparing post- with pre-treatment counts within each group, were 85.7% (day 1), 96.8% (day 7) and 100% (days 28 and 84) for the fluralaner (two-sided two-sample t-test, P ≤ 0.0088 for days 1-84) and 67.5% (day 1), 90.3% (day 7) 99.1% (day 28) for the permethrin group (two-sided two-sample t-test, P ≤ 0.0014 for days 7-28). No lice were seen on fluralaner-treated dogs 28 and 84 days post-treatment. In contrast, two permethrin-treated dogs were re-treated at 7 and 28 days after initial treatment because of observed lice. Owner's perceived pruritus scores were reduced compared to pre-treatment levels by 23.8% (day 1), 31.1% (day 7), 70.4% (day 28) and 99.5% (day 84) after fluralaner treatment and 21.3% (day 1), 45.8% (day 7), and 78.1% (day 28) after permethrin treatment. Dermatological signs were improved compared to pre-treatment levels in both treatment groups. CONCLUSIONS: Single oral fluralaner treatment eliminated natural L. setosus infestation on dogs within 28 days and led to complete dermatological recovery that was maintained until the study end on day 84. Single topical permethrin treatment reduced the number of L. setosus by 99.1% at day 28 although two animals required unscheduled re-treatment.

Efficacy of fluralaner against Otodectes cynotis infestations in dogs and cats.

BACKGROUND: The efficacy of fluralaner for the treatment of Otodectes cynotis infestations in dogs and cats was evaluated after oral (dogs) or topical administration (dogs and cats). Twenty-four dogs and sixteen cats were experimentally infested with O. cynotis and randomly allocated to equal sized groups (n = 8/group). Dog groups were treated once, either orally with fluralaner at a minimum dose of 25 mg/kg body weight, topically with fluralaner at a dose of 25 mg/kg body weight or topically with saline solution (control). Cat groups were treated once, either topically with fluralaner at a dose of 40 mg/kg body weight or topically with saline solution. Ears of all animals were examined otoscopically for live visible mites and the amount of debris and cerumen before, and 14 and 28 days after treatment. Twenty-eight days after treatment, animals were sedated and both ears were flushed to obtain the total number of live mites per animal. The efficacy was calculated, based on the results of the ear flushing, by comparing mean live mite counts in the fluralaner treated groups versus the saline solution treated group. RESULTS: A single topical treatment of cats with fluralaner reduced the mean mite counts by 100% (P < 0.001) at 28 days after treatment. Similarly, a single oral or topical treatment of dogs with fluralaner reduced the mean mite counts by 99.8% (P < 0.001) at 28 days after treatment. Cats treated topically with fluralaner had no mites visible during otoscopic examination at either 14 or 28 days after treatment. All dogs treated orally or topically with fluralaner had no mites visible during otoscopic examination at 28 days after treatment. At 14 days after treatment, only 1-2 mites were visible in three dogs (oral treatment: 2 dogs, topical treatment: 1 dog). All fluralaner-treated animals showed improvement in the amount of cerumen exudation compared with observations performed before treatment. No treatment related adverse events were observed in any dogs or cats enrolled in these studies. CONCLUSIONS: In this study, fluralaner administered topically to cats and orally or topically to dogs was highly effective against Otodectes cynotis mite infestations.

Efficacy of fluralaner administered either orally or topically for the treatment of naturally acquired Sarcoptes scabiei var. canis infestation in dogs.

BACKGROUND: The efficacy of fluralaner, formulated as a chewable tablet (Bravecto™) or topical solution (Bravecto™ Spot-on Solution), was evaluated against naturally acquired Sarcoptes scabiei var. canis infestation in dogs. METHODS: The study was performed in privately-owned dogs naturally infested with S. scabiei var. canis. All dogs living in the same household as the infested dog were enrolled into one of 3 groups (2 fluralaner treated and 1 negative control). All dogs within one household were administered the same treatment, with one dog per household included in further observations and assessments. In total, 29 dogs confirmed positive for sarcoptic mange were included. On Day 0, all dogs in group 1 (n = 9) were treated once orally with fluralaner at a minimum dose of 25 mg/kg body weight; all dogs in group 2 (n = 11) were treated once topically with fluralaner at a dose of 25 mg/kg body weight; and dogs in group 3 (n = 9) were treated once topically with saline solution. Sarcoptes scabiei var. canis mites on each dog were counted before treatment and at 4 weeks after treatment in deep skin scrapings (~4 cm(2)) from 5 different body areas. Clinical signs of infestation (i.e. erythematous papules; casts, scales and crusts; body areas with hair loss) and pruritus were recorded at the same time points. RESULTS: Single oral or topical treatment with fluralaner resulted in a 100 % reduction in mite counts post-treatment (group 1: P = 0.0009 and group 2: P = 0.0011). Resolution of clinical signs at four weeks post-treatment was variable, with improvement observed for erythematous papules, casts and crusts, and pruritus. All fluralaner treated dogs showed an improvement in overall hair re-growth compared with pre-treatment observations. CONCLUSION: Fluralaner administered either orally or topically to naturally infested dogs eliminates Sarcoptes scabiei var. canis mites and improves clinical signs over a 4-week observation period.

The effect of water and shampooing on the efficacy of fluralaner spot-on solution against Ixodes ricinus and Ctenocephalides felis infestations in dogs.

BACKGROUND: Fluralaner spot-on solution provides immediate and persistent efficacy against tick and flea infestations in dogs and cats for 12-weeks following topical administration. The active ingredient fluralaner is distributed systemically following transdermal absorption. Therefore, this study tested the hypothesis whether water-immersion or shampooing of dogs following administration of fluralaner spot-on solution has an impact on subsequent tick and flea efficacy. METHODS: Thirty-two Beagle dogs were allocated to four study groups of 8 dogs each. On day 0, dogs in the 2 treatment groups received topical administration of fluralaner (Bravecto™ spot-on solution) according to label instructions. Dogs in the 2 corresponding control groups remained untreated. On days 3, 21, 49, and 77 dogs in one treatment group and control group were water-immersed for 2-5 min, while dogs in the other treatment group and control group were shampooed 6-8 min with a commercial foaming micro-emulsion, unscented product. On days 4, 28, 56, and 84 all dogs were co-infested with 50 ± 2 female and 10 ± 2 male Ixodes ricinus and 100 ± 4 Ctenocephalides felis, with tick and flea removal and counts 48 ± 2 h post-infestation. Efficacy against ticks and fleas was calculated for each assessment time point. RESULTS: No treatment-related adverse event was observed in any of the 16 dogs treated with fluralaner spot-on solution during the study. Efficacy against ticks at each assessment time point was between 99.7 and 100 % in the water-immersed group and between 99.2 and 100 % in the shampooed group. Efficacy against fleas was 100 % at each assessment time point as well in the water-immersed as the shampooed group. Tick and flea reduction in both treatment groups was significant at all assessment time points (p < 0.0001). CONCLUSIONS: Neither water-immersion nor shampooing after single topical administration of fluralaner spot-on solution had an impact on the excellent tick and flea efficacy over the 12-week recommended re-treatment interval.

Prevention of transmission of Babesia canis by Dermacentor reticulatus ticks to dogs after topical administration of fluralaner spot-on solution.

BACKGROUND: The preventive effect of fluralaner spot-on solution against transmission of Babesia canis by Dermacentor reticulatus ticks was evaluated. FINDINGS: Sixteen dogs, tested negative for B. canis by polymerase chain reaction (PCR) and immunofluorescence assay test (IFAT), were allocated to two study groups. On day 0, dogs in one group (n = 8) were treated once topically with fluralaner spot-on solution (Bravecto™ Spot-on Solution) according to label recommendations and dogs in the control group (n = 8) remained untreated. On days 2, 28, 56, 70 and 84, all dogs were infested with 50 (±4) D. reticulatus ticks harbouring B. canis, with tick in situ thumb counts 48 ± 4 h after each infestation. On day 90, ticks were removed from all dogs and counted. Prior to each infestation, the presence of B. canis in the respective tick batch was confirmed by PCR, and 12-16 % of ticks were found to be infected with B. canis. Efficacy against ticks was 99.5 and 99.3 % on days 4 and 58 after treatment, respectively and 100 % on all other days. Replacement dogs were included for any B. canis infected control dog (in total 19). All control dogs (n = 27) became infected with B. canis, as confirmed by PCR, performed every 7 days, and by IFAT, performed every 14 days after treatment. None of the eight treated dogs became infected with B. canis, as they were tested negative by PCR and IFAT throughout the study until day 112. By comparing infected dogs in the treated group with infected dogs in the untreated control group, a 100 % preventive effect against B. canis transmission was demonstrated. CONCLUSIONS: A single topical administration of fluralaner spot-on solution effectively prevented the transmission of B. canis by infected D. reticulatus ticks over a 12-week period.

Efficacy of fluralaner spot-on solution against induced infestations with Rhipicephalus sanguineus on dogs.

BACKGROUND: The efficacy of fluralaner spot-on solution administered once topically against induced infestations with Rhipicephalus sanguineus was evaluated in dogs over a 12-week post-treatment period. METHODS: Six negative-controlled studies were conducted, involving a total of 112 adult dogs (57 mixed breed, 47 Beagles, eight Labradors). In each study, dogs were randomized to two groups of eight to ten dogs each. On day 0, dogs in each treated group were topically administered fluralaner spot-on solution once at a dose of 25 mg/kg body weight, while dogs in each control group were not treated. Two days before treatment, and on days 28, 56 and 84 after treatment, all dogs were infested with approximately 50 unfed, adult Rh. sanguineus ticks (sex ratio 1:1). Ticks were removed and counted on days 2, 30 (4 weeks), 58 (8 weeks), and 86 (12 weeks) after treatment to assess efficacy. RESULTS: Efficacy against ticks 2 days after treatment was 91.1 % (study 1), 98.4 % (study 2), 100 % (study 3), 97.6 % (study 4), 99.6 % (study 5), and 99.8 % (study 6). At all other assessment time points, tick efficacy was 95.4-100 %. Tick reduction in all treatment groups was significant at all assessment time points (P < 0.0001). CONCLUSIONS: A single topical administration of fluralaner spot-on solution provides a high level of therapeutic and persistent efficacy against Rh. sanguineus ticks over the subsequent 12 weeks.

A quantitative evaluation of the extent of fluralaner uptake by ticks (Ixodes ricinus, Ixodes scapularis) in fluralaner (Bravecto) treated vs. untreated dogs using the parameters tick weight and coxal index.

BACKGROUND: Fluralaner is a new antiparasitic drug that was recently introduced as Bravecto chewable tablets for the treatment of tick and flea infestations in dogs. Most marketed tick products exert their effect via topical application and contact exposure to the parasite. In contrast, Bravecto delivers its acaricidal activity through systemic exposure. Tick exposure to fluralaner occurs after attachment to orally treated dogs, which induces a tick-killing effect within 12 h. The fast onset of killing lasts over the entire treatment interval (12 weeks) and suggests that only marginal uptake by ticks is required to induce efficacy. Three laboratory studies were conducted to quantify the extent of uptake by comparison of ticks' weight and coxal index obtained from Bravecto-treated and negative-control dogs. METHODS: Three studies were conducted using experimental tick infestation with either Ixodes ricinus or Ixodes scapularis after oral administration of fluralaner to dogs. All studies included a treated (Bravecto chewable tablets, MSD Animal Health) and a negative control group. Each study had a similar design for assessing vitality and weighing of ticks collected from dogs of both groups. Additionally, in one study the coxal index (I. ricinus) was calculated as a ratio of tick's ventral coxal gap and dorsal width of scutum. Tick weight data and coxal indices from Bravecto-treated and negative-control groups were compared via statistical analysis. RESULTS: Ticks collected from Bravecto-treated dogs weighed significantly less (p ≤ 0.0108) than ticks collected from negative-control dogs, and their coxal index was also significantly lower (p < 0.0001). The difference in tick weights was demonstrated irrespective of the tick species investigated (I. ricinus, I. scapularis). At some assessments the mean tick weights of Bravecto-treated dogs were significantly lower than those of unfed pre-infestation (baseline) ticks. The demonstrated tick-killing efficacy was in the range of 94.6 - 100%. CONCLUSIONS: Tick weights and coxal indices confirm that a minimal uptake results in a sufficient exposure of ticks to fluralaner (Bravecto) and consequently in a potent acaricidal effect.

Prevention of transmission of Babesia canis by Dermacentor reticulatus ticks to dogs treated orally with fluralaner chewable tablets (Bravecto™).

BACKGROUND: The preventive effect of fluralaner chewable tablets (Bravecto™) against transmission of Babesia canis by Dermacentor reticulatus ticks was evaluated. METHODS: Sixteen dogs, tested negative for B. canis by PCR and IFAT, were allocated to two study groups. On day 0, dogs in one group (n = 8) were treated once orally with a fluralaner chewable tablet according to label recommendations and dogs in the control group (n = 8) remained untreated. On days 2, 28, 56, 70 and 84, dogs were infested with 50 (±4) B. canis infected D. reticulatus ticks with tick in situ thumb counts 48 ± 4 h post-infestation. Prior to each infestation, the D. reticulatus ticks were confirmed to harbour B. canis by PCR analysis. On day 90, ticks were counted and removed from all dogs. Efficacy against ticks was calculated for each assessment time point. After treatment, all dogs were physically examined in conjunction with blood collection for PCR every 7 days, blood samples for IFAT were collected every 14 days and the dog's rectal body temperature was measured thrice weekly. From dogs displaying symptoms of babesiosis or were PCR positive, a blood smear was taken, and, if positive, dogs were rescue treated and replaced with a replacement dog. The preventive effect was evaluated by comparing infected dogs in the treated group with infected dogs in the untreated control group. RESULTS: All control dogs became infected with B. canis, as confirmed by PCR and IFAT. None of the 8 treated dogs became infected with B. canis, as IFAT and PCR were negative throughout the study until day 112. Fluralaner chewable tablet was 100 % effective against ticks on days 4, 30, 58, and 90 and an efficacy of 99.6 % and 99.2 % was achieved on day 72 and day 86 after treatment, respectively. Over the 12-week study duration, a 100 % preventive effect against B. canis transmission was demonstrated. CONCLUSIONS: A single oral administration of fluralaner chewable tablets effectively prevented the transmission of B. canis by infected D. reticulatus ticks over a 12-week period.

Efficacy of orally administered fluralaner (Bravecto™) or topically applied imidacloprid/moxidectin (Advocate®) against generalized demodicosis in dogs.

BACKGROUND: This laboratory study compared the efficacy of Bravecto™ (fluralaner), formulated as a chewable tablet, with the efficacy of Advocate® (imidacloprid/moxidectin), formulated for topical administration, against naturally acquired generalized demodicosis in dogs. METHODS: Sixteen dogs, all diagnosed with generalized demodectic mange, were randomly allocated to two equal groups. Bravecto™ chewable tablets were administered once orally at a minimum dose of 25 mg fluralaner/kg body weight to one group of dogs, while the second group was treated topically on three occasions at 28-day intervals with Advocate® at a minimum dose of 10 mg imidacloprid/kg body weight and 2.5 mg moxidectin/kg body weight. Mites were counted in skin scrapings and demodectic lesions were evaluated on each dog before treatment and at 28-day intervals thereafter over a 12 week study period. Deep skin scrapings (~4 cm(2)) were made from the same five sites on each dog at each subsequent examination. RESULTS: After single oral administration of Bravecto™ chewable tablets, mite numbers in skin scrapings were reduced by 99.8% on Day 28 and by 100% on Days 56 and 84. Mite numbers in the dogs treated topically on three occasions at 28-day intervals with Advocate® were reduced by 98.0% on Day 28, by 96.5% on Day 56 and by 94.7% on Day 84. Statistically significantly (P ≤ 0.05) fewer mites were found on Days 56 and 84 on the Bravecto™ treated dogs compared to Advocate® treated dogs. A marked decrease was observed in the occurrence of erythematous patches, crusts, casts and scales in the dogs treated with Bravecto™ and in the occurrence of erythematous patches in the dogs treated with Advocate®. With the exception of one dog in each treated group, all dogs exhibited hair regrowth ≥ 90% at the end of the study in comparison with their hair-coat at study start. CONCLUSIONS: Single oral administration of Bravecto™ chewable tablets is highly effective against generalized demodicosis, with no mites detectable at 56 and 84 days following treatment. In comparison, Advocate®, administered three times at 28-day intervals, is also highly effective against generalized demodicosis, but most dogs still harboured mites at all assessment time points. Both treatments resulted in a marked reduction of skin lesions and increase of hair re-growth 12 weeks after the initial treatment.

Onset of activity of fluralaner (BRAVECTO™) against Ctenocephalides felis on dogs.

BACKGROUND: Fluralaner (Bravecto™) is a novel systemic insecticide and acaricide that provides long persistent antiparasitic activity following a single administration at the minimum dose of 25 mg/kg body weight. METHODS: Three negative controlled, randomized studies were conducted in dogs to evaluate the start to kill (1 study) and the speed of flea kill (2 studies) of fluralaner. All dogs were infested prior to treatment with unfed adult C. felis fleas. Dogs in the treated groups were administered once orally with fluralaner at a minimum dose of 25 mg/kg body weight, while dogs in the control groups were not treated. Separate control and treatment groups were paired at each time point of flea assessment. Flea counts were performed by combing dogs at either 0.5, 1, 2, or 4 hours after fluralaner treatment to measure the start to kill. To evaluate the speed of flea kill over 12 weeks, flea counts were performed by combing dogs at either 4, 8, 12, or 24 hours after fluralaner treatment and then at 4, 8, 12, or 24 hours after each flea re-infestations performed at 4, 8, and 12 weeks following treatment. RESULTS: In the start to kill study, the fluralaner activity against fleas started already at 1 hour post-treatment (8% numerical efficacy). At 2 and 4 hours post-treatment, the flea reduction was significant with 36.7% and 88% efficacy, respectively. In the speed of kill studies, the efficacy against fleas after fluralaner treatment was 80.5% at 4 hours and remained ≥ 99.4% at 8, 12 and 24 hours. After flea re-infestations in weeks 4, 8 and 12, the efficacy at 4 hours was 96.8, 91.4, and 33.5%, respectively. Efficacy at 8, 12 and 24 hours after flea re-infestations was 98.0-100% for the 12 weeks of the study. Except for 4 hours after the 12-week flea re-infestation, flea reduction was significant for all time points after flea re-infestation. CONCLUSIONS: Single oral fluralaner administration rapidly eliminates existing flea infestations and provides excellent protection against fleas over 12 weeks following treatment.