Year-round efficacy of a single treatment of fluralaner injectable suspension (Bravecto QuantumTM) against repeated infestations with Ixodes holocyclus in dogs.

BACKGROUND: The longer the duration of protection of an acaricide against canine infestation with Ixodes holocyclus, the lower the risk of gaps in tick control programs that will place dogs at risk of potentially fatal tick-induced paralysis. Two studies investigated the duration of efficacy provided by a novel injectable suspension of fluralaner (Bravecto QuantumTM) against this tick species. METHODS: In both studies, 20 clinically healthy dogs were randomized to an untreated control group or to a group treated once, on Day 0, with the injectable fluralaner suspension (15 mg/kg). Dogs were infested with up to 25 unfed adult female I. holocyclus ticks on Day -1, during Weeks 1 and 2, and then at intervals no greater than approximately 3 months for the 13 months following treatment. Ticks were assessed in situ at 24 and 48 h and assessed and removed at 72 h following treatment and each subsequent infestation. Efficacy was determined by comparing arithmetic mean live tick (attached or free) counts in the treated group with the control group. RESULTS: The untreated control dogs maintained adequate infestations for efficacy evaluations at all assessment weeks, with mean tick counts ranging from 16.2 to 21.6 in Study 1 and 14.0 to 23.5 in Study 2. The efficacy of fluralaner injectable suspension against existing infestations, determined 72 h following treatment administration, was 64.1% in Study 1 and 42.7% in Study 2. Efficacy against post-treatment infestations in Study 1 ranged from 95.7 to 100% from Week 1 through Week 57; in Study 2 efficacy was 100% at every assessment from Week 1 through Week 57. No treatment-related adverse events were recorded in either study. CONCLUSION: The injectable fluralaner suspension was highly effective against I. holocyclus infestations of dogs from one week through 13 months following a single treatment. By placing treatment with the veterinarian, killing ticks within 72 h of attachment, and providing a full year of protection, fluralaner injectable suspension can help facilitate owner compliance with tick control treatment recommendations, thus reducing the risk of canine tick paralysis.

Year-round efficacy of a single treatment of fluralaner injectable suspension (Bravecto Quantum™) against repeated infestations with Rhipicephalus sanguineus (sensu lato) and Ctenocephalides felis in dogs.

BACKGROUND: Poor owner compliance with monthly control measures means that dogs in Australia can remain susceptible to infestations with fleas, present throughout the whole year, and brown dog ticks, which thrive in tropical and subtropical areas. A 150 mg/ml injectable fluralaner suspension (Bravecto Quantum™) was developed to help ensure year-round protection against these parasites. A study investigated the persistent efficacy of this formulation against repeated challenges with Rhipicephalus sanguineus (sensu lato) and Ctenocephalides felis throughout 12 months following a single subcutaneous treatment. METHODS: Twenty dogs were blocked by pre-treatment R. sanguineus s.l. counts and randomized to an untreated control group or to a group treated once, on day 0, with the fluralaner injection (15 mg/kg). Infestations of 50 mixed-sex, unfed adult R. sanguineus s.l. and up to 100 C. felis were done on days 7, 14, 35, 63, 91, 126, 154, 182, 210, 245, 273, 301, 336 and 365. Live flea and tick counts were completed 48 h post-infestation. Flea infestations were also done on day -1, with counts on day 2. Infestations were considered adequate if at each evaluation, at least six dogs in the control group retained at least 20% of tick challenges and 25% of flea challenges. RESULTS: The fluralaner injectable suspension was well tolerated. Efficacy against existing flea infestations was > 99% (arithmetic and geometric means) at 48 h post-treatment. At all subsequent assessments throughout the year following treatment, efficacy against fleas remained at 100%. Arithmetic mean tick count reductions relative to the control group ranged from 97.6% to 100% from day 7 through 11 months and was 92.6% at 12 months (geometric means 95.2% to 100% through 12 months). CONCLUSION: The injectable fluralaner suspension was effective against fleas and brown dog ticks for 12 months following a single treatment. Compared with more frequently administered products where compliance may be suboptimal, the year-round efficacy of this veterinarian-administered fluralaner formulation has the potential to improve owner compliance for control of fleas and ticks. In turn, by reducing the detrimental effects of flea and tick infestations and risk of transmission of flea- and tick-borne pathogens, canine health can be enhanced.

Efficacy of a spot-on combination of fluralaner plus moxidectin (Bravecto® Plus) in cats following repeated experimental challenge with a field isolate of Ctenocephalides felis.

BACKGROUND: A spot-on formulation of fluralaner plus moxidectin has been designed to provide long-term protection against fleas and ticks, prevent heartworm disease and treat gastrointestinal nematode infections in cats. The objective of this study was to determine the efficacy of this product against fleas collected from a household with repeated fipronil failures following owner-administered treatments. METHODS: Thirty cats were randomized to three equal groups: (A) untreated controls; (B) to receive a single application of fluralaner plus moxidectin (Bravecto® Plus) at 40 mg/kg and 2 mg/kg body weight, respectively; and (C) three applications at one month intervals with a spot-on formulation of fipronil and (S)-methoprene (Frontline® Plus) at 0.5 ml manufacturer recommended dose. Flea challenges were completed on Days -6 (for randomization), -1, 7, 14, 28, 42, 56, 70, 77, 84 and 91. Flea counts were completed 48 hours after initial treatment and 48 hours following each subsequent challenge. RESULTS: Fleas were found on all control and all fipronil and (S)-methoprene treated cats at every assessment. From Day 2 to Day 93, all cats in the fluralaner plus moxidectin group were flea-free, with one exception (Day 58; three fleas counted on one cat); control group flea counts ranged between 34-109, and fipronil and (S)-methoprene group counts ranged between 1-79. At each assessment after Day 0, compared to the control group, geometric mean flea counts were significantly lower in the fipronil and (S)-methoprene group (P ≤ 0.04) and in the fluralaner plus moxidectin group (P < 0.001), and mean flea counts in the fluralaner plus moxidectin group were significantly lower than those of the fipronil and (S)-methoprene group (P < 0.001). The efficacy of fluralaner plus moxidectin, based on geometric means, was 100% at each assessment post-Day 0 except on Day 58 when efficacy was 99.7%. In the fipronil and (S)-methoprene group efficacy ranged between 30.6-65.6%. CONCLUSIONS: These findings demonstrate complete efficacy of fluralaner plus moxidectin against a flea isolate that was not controlled by fipronil and (S)-methoprene. This study provides confirmation of the consistent, sustained efficacy of topically applied fluralaner in the treatment and control of flea infestations in cats.

Safety of topical administration of fluralaner plus moxidectin concurrently with praziquantel in cats.

BACKGROUND: Fluralaner provides efficacy against feline ectoparasites following topical administration. Moxidectin is routinely used to treat gastrointestinal nematode infections and prevent heartworm disease caused by Dirofilaria immitis. Praziquantel is routinely used to treat feline tapeworm infections. The safety of a fluralaner plus moxidectin combination topical solution (Bravecto™ Plus, MSD Animal Health) was assessed when administered concurrently with a commercially available praziquantel topical solution (Droncit™ Spot-on, Bayer Animal Health GmbH). The highest dose rates in clinical use were tested. RESULTS: Concurrent topical administration of a fluralaner plus moxidectin and a praziquantel product did not result in adverse findings. One out of ten cats receiving praziquantel only (control group), and two out of ten cats receiving fluralaner plus moxidectin and praziquantel (treatment group) had dandruff-like flakes in their coat at the application site. Two out of the ten control cats and three cats out of the ten treatment group cats had very small amounts of unidentified material (minute crusts or crumbs) at the application site which was only visible during close inspection. CONCLUSIONS: The concurrent treatment of cats with fluralaner plus moxidectin and praziquantel at the maximum dose in clinical use was well tolerated.

Investigation of the efficacy of fluralaner spot-on (Bravecto®) against infestations of Ixodes holocyclus on cats.

BACKGROUND: Infestation of cats with the Australian paralysis tick, Ixodes holocyclus continues to be a threat because of the paralysis that can result from attachment of just a single tick. The outcome can be fatal, particularly if tick removal and treatment is not initiated soon after the onset of paralysis. However, there are no published studies to guide veterinarians and owners on preventive measures. A study was therefore initiated to determine the efficacy of a systemically-acting, spot-on formulation of fluralaner (Bravecto®) for cats against existing I. holocyclus infestations, and to investigate the duration of protection following a single administration. METHODS: Healthy domestic cats, short or long-hair, immunized against holocyclotoxin, were randomly allocated to two groups of 10 cats per group, to receive either a single topically applied fluralaner treatment or no treatment. Fluralaner treatments were administered on Day 0 at a dose rate of 40 mg/kg. All cats were infested with 10 adult unfed female I. holocyclus on Day -1 and on Days 14, 28, 42, 56, 70 and 84. Ticks were assessed at 24 and 48 h after fluralaner treatment and 24, 48 and 72 hours after each subsequent re-infestation. Ticks were counted but not removed at the 24- and 48-h post-challenge assessments and were removed following the 72-h counts. RESULTS: The efficacy of fluralaner spot-on against an existing I. holocyclus infestation was 100% at 48 h post treatment. Following re-infestations, efficacy remained at 100% at the 72-h assessments for all challenges from Day 14 to Day 84. Differences between mean live tick counts on treated versus control cats were significant at all time points from the first post-treatment assessment (t-test: t(18) = 23.162; P < 0.0001) through the final challenge on Day 84 (t-test: t(18) = 21.153; P < 0.0001). No treatment-related adverse events were observed and there were no abnormal observations at the product application sites. CONCLUSIONS: A single treatment of fluralaner spot-on was well tolerated and provided 100% efficacy against I. holocyclus ticks for at least 84 days. Fluralaner spot-on can be a valuable tool to prevent tick infestation in cats, and to control the risk of I. holocyclus-induced paralysis.

A small-scale open-label study of the treatment of canine flea allergy dermatitis with fluralaner.

BACKGROUND: Fluralaner is an isoxazoline systemic insecticide and acaricide that provides persistent flea-killing activity on dogs for 12 weeks. European and US field studies have shown that fluralaner treatment alleviates the signs of flea allergy dermatitis (FAD) in client-owned dogs. HYPOTHESIS/OBJECTIVE: To assess the clinical response in FAD affected dogs over the 12-week period following a single oral fluralaner treatment. ANIMALS: Twenty client-owned dogs were diagnosed with FAD on the basis of compatible clinical signs and a positive response in flea antigen tests, using intradermal and or serological methods. METHODS: An open-label small-scale study with all dogs receiving a single oral fluralaner treatment. All enrolled dogs were diagnosed with FAD and then clinically monitored at 4-week intervals for 12 weeks. Twenty dogs completed the study. RESULTS: All dogs were flea-free at all post-treatment assessments except for one dog that had a single flea at the first post-enrollment assessment at 4 weeks. At the 4-week post-treatment assessment active FAD signs had resolved in all dogs; at 8 weeks post-treatment, two dogs showed mild signs. All clinical signs of FAD had resolved at the final assessment of 12 weeks after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: A single administration of fluralaner alleviated or resolved signs associated with FAD in all treated dogs over the recommended 12-week treatment period.

A randomized controlled trial of the efficacy of orally administered fluralaner (Bravecto™) against induced Ixodes holocyclus (Australian paralysis tick) infestations on dogs.

BACKGROUND: Ixodes holocyclus ticks are a frequently fatal threat to dogs in eastern Australia. These ticks secrete a neurotoxin that can produce an ascending paralysis after 72 h attachment that can lead to death in affected animals. Fluralaner is a potent systemic acaricide with immediate and persistent efficacy for tick control including evidence of 100% efficacy against Ixodes ricinus ticks within 72 h. This study investigated the potential for oral fluralaner administration to control I. holocyclus infestation and the subsequent risk of host paralysis. METHODS: Healthy Foxhound and Foxhound cross dogs immunized against holocyclotoxin were randomly allocated to receive either a single fluralaner (at least 25 mg/kg) dose or no treatment. All dogs were penned individually and infested with 30 adult unfed female I. holocyclus 1 day before treatment and 14, 28, 42, 56, 70, 84, 112 and 140 days following treatment. Ticks were counted and assessed at 24, 48 and 72 h after the initial fluralaner treatment and after each subsequent infestation. Ticks were not removed at the 24 and 48 h assessments, but were removed after the 72 h assessments. On 112 and 140 days post treatment a new group of untreated control dogs was used. RESULTS: Fluralaner treatment efficacy against I. holocyclus was 100% at 72 h post treatment. Following re-infestations the efficacy remained at 100% at the 72 h assessments for 115 days and reached 95.7% at 143 days. The differences between mean live tick counts on treatment and control groups were significant (P < 0.00l) at all assessment time points for 143 days following treatment. CONCLUSIONS: Oral fluralaner treatment can prevent Australian paralysis tick infestations for at least 115 days.

Safety of concurrent treatment of dogs with fluralaner (Bravecto™) and milbemycin oxime-praziquantel.

BACKGROUND: Fluralaner (Bravecto™; Merck/MSD Animal Health) is a novel systemic ectoparasiticide for dogs providing long-acting flea and tick control after a single oral dose. Milbemycin oxime and praziquantel are routinely used to control Dirofilaria immitis and intestinal worm infections in dogs. The safety of concurrent use of fluralaner and a commercially available milbemycin oxime plus praziquantel combination tablet, in particular with regard to gastrointestinal symptoms, was investigated using oral doses at or above the maximum recommended rates. FINDINGS: Some minor and transient clinical findings were observed during the study period; however, none of these was considered to be related to concurrent treatment with fluralaner and milbemycin oxime plus praziquantel, or to the use of either product alone. CONCLUSIONS: Concurrent treatment with fluralaner, milbemycin oxime and praziquantel is well tolerated in dogs.

An open, self-controlled study on the efficacy of topical indoxacarb for eliminating fleas and clinical signs of flea-allergy dermatitis in client-owned dogs in Queensland, Australia.

BACKGROUND: Canine flea-allergy dermatitis (FAD), a hypersensitivity response to antigenic material in the saliva of feeding fleas, occurs worldwide and remains a common presentation in companion animal veterinary practice despite widespread availability of effective systemic and topical flea-control products. HYPOTHESIS/OBJECTIVES: To evaluate the clinical response in dogs with FAD treated topically with indoxacarb, a novel oxadiazine insecticide. ANIMALS: Twenty-five client-owned dogs in Queensland, Australia diagnosed with pre-existing FAD on the basis of clinical signs, flea-antigen intradermal and serological tests. METHODS: An open-label, noncontrolled study, in which all dogs were treated with topical indoxacarb at 4 week intervals, three times over 12 weeks. RESULTS: Twenty-four dogs completed the study. Complete resolution of clinical signs of FAD was observed in 21 cases (87.5%), with nearly complete resolution or marked improvement in the remaining three cases. Mean clinical scores (Canine Atopic Dermatitis Extent and Severity Index-03) were reduced by 93.3% at week 12. Mean owner-assessed pruritus scores were reduced by 88% by week 12. Mean flea counts reduced by 98.7 and 100% in weeks 8 and 12, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Topical indoxacarb treatment applied every 4 weeks for 12 weeks, without concomitant antipruritic or ectoparasiticide therapy, completely alleviated flea infestations in all dogs and associated clinical signs of FAD in a high proportion of this population of dogs in a challenging flea-infestation environment.

Safety of the concurrent treatment of dogs with Bravecto (fluralaner) and Scalibor protectorband (deltamethrin).

BACKGROUND: Bravecto (fluralaner; MSD Animal Health) is a novel systemic ectoparasiticide for dogs providing long-acting flea- and tick-control after a single oral dose. Scalibor Protectorband (deltamethrin; MSD Animal Health) is a collar often used to reduce sandfly feeding for leishmaniasis prevention. This study investigated the safety of the concurrent use of Bravecto and Scalibor Protectorband at the recommended dosage regimens. FINDINGS: Throughout the study period of 24 weeks, there were no clinical findings related to the concurrent treatment with Bravecto in dogs fitted with Scalibor Protectorband at the recommended dosage regimen. CONCLUSIONS: Concurrent treatment with Bravecto in dogs fitted with Scalibor Protectorband is well tolerated.

Discovery of ectoparasiticidal hydrazonotrifluoromethanesulfonanilides.

A series of hydrazonotrifluorosulfonanilide derivatives were synthesized and evaluated for in vitro activity against the ectoparasites Ctenocephalides felis and Rhipicephalus sanguineus. Some compounds with excellent activity against tick were identified.

Parasiticidal 2-alkoxy- and 2-aryloxyiminoalkyl trifluoromethanesulfonanilides.

A series of novel 2-alkoxy- and 2-aryloxyiminoalkyl trifluoromethanesulfonanilide derivatives have shown significant in vitro parasiticidal activity against the ectoparasites Ctenocephalides felis and Rhipicephalus sanguineus. A number of these compounds also displayed significant in vitro endoparasite activity against the nematode Haemonchus contortus.