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A QUANTITATIVE EVALUATION OF THE EXTENT OF FLURALANER UPTAKE BY TICKS (IXODES RICINUS, LXODES SCAPULARIS) IN FLURALANER (BRAVECTO™) TREATED VS. UNTREATED DOGS USING THE PARAMETERS TICK WEIGHT AND COXAL INDEX

Heike Williams, Janina Demeler, Janina Taenzler, Rainer KA Roepke, Eva Zschiesche and Anja R Heckeroth

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Abstract

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.

 

Keywords: Bravecto™ chewable tablets, Fluralaner, Dog, Tick weight, Coxal index, Ixodes ricinus, Ixodes scapularis, Efficacy

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A RANDOMIZED CONTROLLED TRIAL OF THE EFFICACY OF ORALLY ADMINISTERED FLURALANER (BRAVECTO™) AGAINST INDUCED IXODES HOLOCYCLUS (AUSTRALIAN PARALYSIS TICK) INFESTATIONS ON DOGS

Petr Fisara and Maurice Webster

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Abstract

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.

 

Keywords: Dog, Fluralaner, Tick, Paralysis, Australia, Ixodes holocyclus

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A RANDOMIZED, BLINDED CONTROLLED AND MULTI-CENTERED FIELD STUDY COMPARING THE EFFICACY AND SAFETY OF BRAVECTO™ (FLURALANER) AGAINST FRONTLINE™ (FIPRONIL) IN FLEA- AND TICK-INFECTED DOGS

Nadja Rohdich, Rainer KA Roepke and Eva Zschiesche

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Abstract

Background: Fluralaner, a new molecular entity of the isoxazoline class, has potent insecticidal and acaricidal activity and can be safely administered orally to dogs.

Methods: A randomized, investigator-blinded, multi-centered field study compared the flea- and tick-control efficacy for dogs over a 12-week period with either a single oral dose of Bravecto™ (fluralaner) formulated as a chewable tablet or with three sequential topical Frontline™ (fipronil) treatments. Individual dogs were the experimental unit for ticks and households were the experimental unit for fleas. A total of 108 tick-infested dogs were treated with Bravecto™ (fluralaner) and 54 tick-infested dogs were treated with Frontline™ (fipronil). Dogs in 115 flea-infested households received Bravecto™ (fluralaner) and dogs in 61 flea-infested households received Frontline™ (fipronil). Flea and tick counts were conducted on all dogs at weeks 2, 4, 8, and 12 following initial treatment and efficacy was calculated as the mean percent reduction in tick or flea count at each time point compared with the mean pretreatment initiation count for each treatment group. Additionally, the percentages of tick-free and flea-free households were determined.

Results: At weeks 2, 4, 8, and 12, Bravecto™ (fluralaner) flea-control efficacy in treated households was 99.2%, 99.8%, 99.8%, and 99.9% respectively, while Frontline™ (fipronil) efficacy was 94.1%, 93.0%, 96.0%, and 97.3%, respectively. Bravecto™ (fluralaner) tick-control efficacy on treated dogs at weeks 2, 4, 8, and 12 was 99.9%, 99.9%, 99.7%, and 100%, respectively, and Frontline™ (fipronil) tick efficacy was 97.6%, 93.8%, 100%, and 100%, respectively. Of dogs showing clinical flea allergy dermatitis (FAD) signs at the study start, 85.7% in the Bravecto™ (fluralaner)-treated group and 55.6% in the Frontline™ (fipronil)-treated group were evaluated at each time point as showing no clinical signs of FAD until study completion.

Conclusions: Bravecto™ (fluralaner) administered once orally to dogs in a chewable tablet was highly effective for 12 weeks against fleas and ticks on privately-owned dogs and was significantly non-inferior (ticks) and superior (fleas) in comparison with topical Frontline™ (fipronil) administered 3 times sequentially.

 

Keywords: Fleas, Ticks, Bravecto™ (fluralaner), Isoxazoline, Frontline™ (fipronil), Efficacy, Field study, Dog

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A RANDOMIZED, BLINDED, CONTROLLED USA FIELD STUDY TO ASSESS THE USE OF FLURALANER TABLETS IN CONTROLLING CANINE FLEA INFESTATIONS

Cheyney Meadows, Frank Guerino and Fangshi Sun

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Abstract

Background: The novel isoxazoline molecule fluralaner provides 12 weeks activity against fleas and 8 to 12 weeks against tick infestations according to label claims.

Methods: This blinded, multi-center study in client-owned dogs evaluated the flea control provided by a single oral fluralaner treatment (25–56 mg/kg; Bravecto™, Merck Animal Health) compared to a control group administered three oral spinosad (30 – 60 mg/kg; Comfortis®, Elanco) treatments at 4-week intervals together with an amitraz collar (9%, Preventic®, Virbac). Households were randomized (3:1 ratio) to either fluralaner (224 dogs, 118 households) or control (70 dogs, 39 households). Within households, one primary dog with at least 10 live fleas at enrollment was randomly selected for whole body flea counts every 4 weeks through Week 12; all dogs were followed for safety until Week 12. Fluralaner dogs received two additional doses at Weeks 12 and 24 for further safety and palatability observations through Week 26.

Results: Geometric mean flea count reductions from baseline for the fluralaner group at Weeks 4, 8, and 12 were 99.7%, 99.8%, and 99.8%, respectively; and 96.1%, 99.5%, and 99.6% for the spinosad controls. Percentages of flea-free primary dogs at Weeks 4, 8, and 12 were 91.1%, 95.4%, and 95.3% for the fluralaner group; and 44.7%, 88.2%, and 84.4% for the controls; the differences were significant at Weeks 4 (P < 0.0001) and 12 (P = 0.0370). Improvements in veterinarian assessed flea allergy dermatitis (FAD) were observed in both groups. Fluralaner tablets were accepted free choice in over 90% of doses. The most common adverse event was vomiting, occurring in 7.1% of the fluralaner group and 14.3% of the controls. No treatment related serious adverse events were reported.

Conclusions: A single treatment of dogs with the palatable fluralaner flavored chewable tablet provides a safe and effective option for 12 weeks of flea control at least equivalent to that of 3 sequential treatments with spinosad tablets. Linked to the high level of flea control was a substantial alleviation of associated signs of FAD.

 

Keywords: Fluralaner, Fleas, Spinosad, Efficacy, Safety, Field study

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A RANDOMIZED, BLINDED, CONTROLLED USA FIELD STUDY TO ASSESS THE USE OF FLURALANER TOPICAL SOLUTION IN CONTROLLING CANINE FLEA INFESTATIONS

Cheyney Meadows, Frank Guerino and Fangshi Sun

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Abstract

Background: Orally administered fluralaner effectively controls fleas and ticks on dogs for 12 weeks. This study evaluates the flea control efficacy achieved with topically applied fluralaner in dogs.

Methods: This investigator-blinded, multi-center randomized, positive controlled study evaluated flea control efficacy in dogs following a single owner-applied treatment of topical fluralaner. A positive control group received three treatments, at 4-week intervals, of a commercial formulation of fipronil/(S)-methoprene. All dogs in households randomized to the fluralaner group were dispensed an initial treatment at enrollment and a second treatment at week 12 for an additional 3-week observation of treatment safety. Households with up to five healthy dogs, all at least 12 weeks of age and weighing at least 2 kg (4.4 lb), were randomized in a ratio of 3:1 of fluralaner to positive control. Within households, one primary dog with at least 10 live fleas at enrollment was randomly selected. Flea counts were performed on all primary dogs every 4 weeks through week 12. Efficacy measurement was based on reduction from baseline flea counts. Treatment was considered effective if geometric mean live flea count reductions at weeks 4, 8, and 12 were 90% or greater and significantly different from counts at enrollment. In addition, for each time point the arithmetic mean live flea counts, the efficacy based on arithmetic means, the number and percentage of dogs with at least a 90% reduction in flea count, and the number and percentage of flea free dogs were calculated. Statistical comparisons were also made between treatment groups.

Results: At 12 sites, across 10 states, 121 households (221 dogs) were randomized to receive fluralaner and 44 households (100 dogs) were randomized to receive the positive control. Fluralaner was demonstrated to be significantly effective (all P ≤ 0.0001) at 4 weeks (99.8% reduction), 8 weeks (99.9%), and 12 weeks (99.9%). The positive control was significantly different from baseline (all P ≤ 0.0001) and showed a reduction of 81.2% at 4 weeks and was effective at 8 weeks (90.3%) and 12 weeks (93.0%). Arithmetic mean flea count reductions for the fluralaner group at 4, 8, and 12 weeks were 99.8, 99.9, and 99.9%, respectively. For the positive control, arithmetic mean flea count reductions were 58.8, 75.3, and 80.8% at 4, 8, and 12 weeks, respectively. No treatment-related serious adverse events were reported in either group.

Conclusions: Owner-applied topical fluralaner treatment was safe in dogs and provided ≥ 99.8% flea control efficacy for 12 weeks.

 

Keywords: Bravecto, Fluralaner, Fleas, Fipronil-methoprene, Dogs

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A RANDOMIZED, BLINDED, CONTROLLED USA FIELD STUDY TO ASSESS THE USE OF FLURALANER TOPICAL SOLUTION IN CONTROLLING FELINE FLEA INFESTATIONS

Cheyney Meadows, Frank Guerino and Fangshi Sun

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Abstract

Background: Fleas are a common ectoparasite of domestic cats and there is a need for novel treatments that improve feline flea control.

Methods: This investigator-blinded, multi-center randomized, positive-controlled study evaluated the flea control in cats provided by a single owner-applied treatment with a fluralaner topical formulation compared with a positive control. Households with up to five healthy cats, all at least 12 weeks of age and weighing at least 1.2 kg (2.6 lb), were randomized in an approximate 3:1 ratio of fluralaner to positive control. All cats in households randomized to the positive control group were dispensed three treatments, at 4-week intervals, of a commercial formulation of fipronil/(S)-methoprene. All cats in households randomized to the fluralaner group were dispensed an initial treatment at enrollment and a second treatment at week 12 for an additional 3-week observation of treatment safety. One primary cat with at least five live fleas at enrollment was randomly selected within each household. Flea counts were performed on all primary cats at 4-week intervals through week 12. Efficacy measurement was based on reduction in flea counts from baseline. Treatment was considered effective at weeks 4, 8 and 12 if mean live flea count reductions were 90% or greater and statistically significantly different (P ≤ 0.05) from counts at enrollment.

Results: In 18 investigational veterinary clinics across 11 USA states, 116 households (224 cats) were randomized to receive topical fluralaner and 45 households (87 cats) were randomized to the fipronil-methoprene combination. Fluralaner was demonstrated to be effective at 4 weeks (99.1% flea count reduction), 8 weeks (99.5%), and 12 weeks (99.0%), and all reductions were significantly different from the enrollment count (all P < 0.0001). The fipronilmethoprene combination was < 90% effective at each post-treatment assessment, with peak efficacy of 75.4% at 12 weeks (all P < 0.0001). No treatment-related serious adverse events were reported in either group.

Conclusions: Owner-applied fluralaner topical treatment was safe in cats and was highly effective in killing fleas over the subsequent 12 weeks.

Keywords; Bravecto, Fluralaner, Fleas, Fipronil-methoprene, Cats

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ASSESSMENT OF DOG OWNER ADHERENCE TO VETERINARIANS’ FLEA AND TICK PREVENTION RECOMMENDATIONS IN THE UNITED STATES USING A CROSS-SECTIONAL SURVEY

Robert P. Lavan, Kaan Tunceli, Dongmu Zhang, Dorothy Normile and Rob Armstrong

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Abstract

Background: Adherence to a prescribed therapeutic regimen is a critical factor for achieving medication effectiveness and therefore treatment success. In the case of companion animal ectoparasite control, suboptimal owner adherence to medication recommendations is thought to be a common cause of treatment failure, and previous reports have found pet owners applying an average of 4.0–4.6 monthly flea and tick treatments per year to their dogs. This study investigated: US veterinary hospital self-reported flea and tick prevention recommendations; dog owner recollection of these recommendations; dog owner opinion on flea/tick recommendations and estimated owner flea and tick medication adherence based on veterinary hospital purchase records.

Results: Veterinarians at 24 veterinary hospitals in 4 United States regions provided their flea and tick prevention recommendations. Five hundred fifty-nine dog owners, clients of the 24 hospitals, completed a survey evaluating their recollection of the hospitals’ recommendations and their opinions regarding required treatment frequency. Almost all veterinary hospitals in this study recommended 12 months of flea and tick prevention but only 62% of participating dog owners recalled this recommendation. The average owner response was that their dogs require 10.5 months of flea and tick prevention annually. Owner opinions were significantly different among U.S. regions with pet owners in the northeast U.S. believing that they needed significantly less canine flea and tick protection than pet owners in other parts of the United States. The estimated actual flea and tick prevention coverage was 6.1 months based on owner medication purchases over a 12-month period.

Conclusions: In the United States, dog owner opinions and actions show that their flea and tick treatment adherence falls short of veterinarians’ recommendations.

 

Keywords: Compliance, Adherence, Flea, Tick, Dog, Fluralaner, Ectoparasites

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COMPARATIVE PHARMACOKINETICS OF FLURALANER IN DOGS AND CATS FOLLOWING SINGLE TOPICAL OR INTRAVENOUS ADMINISTRATION

Susanne Kilp, Diana Ramirez, Mark J Allan and Rainer KA Roepke

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Abstract

Background: Bravecto™ Chewable Tablets for Dogs, containing fluralaner as active ingredient, is an innovative treatment for flea and tick infestations that provides safe, rapid and long acting efficacy after a single oral administration in dogs. Topically applied fluralaner provides similar safe, rapid and long acting efficacy, both in dogs and in cats. The pharmacokinetic profile of fluralaner was evaluated in dogs and in cats following either topical or intravenous administration.

Methods: Twenty-four dogs and 24 cats received three different topical doses, with the mid-dose based on the respective minimum recommended dose, and one intravenous dose. Plasma samples were collected for 112 days and fluralaner concentrations were quantified using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method. Pharmacokinetic parameters were calculated using non-compartmental methods.

Results: In dogs, fluralaner was readily absorbed from the topical administration site into the skin, subjacent tissues and blood. Fluralaner plasma concentrations showed an apparent plateau between ~ day 7 and 63, with individual tmax seen within this time period. After the plasma plateau, concentrations declined slowly and were quantifiable for more than 12 weeks. In cats, fluralaner was readily systemically absorbed from the topical administration site, reaching maximum concentrations (Cmax) in plasma between 3 and 21 days post administration, after which concentrations declined slowly, and were also quantifiable for more than 12 weeks. Systemic exposure, as shown by Cmax and the area under the concentration versus time curve from time 0 to the last measurable concentration (AUC(0→t)) increased proportionally with dose in both species. Following intravenous administration fluralaner showed a relatively high apparent volume of distribution (Vz), a low plasma clearance (Cl), a long terminal half-life (t1/2) and a long mean residence time (MRT); thereby demonstrating a long persistence of fluralaner in both species.

Conclusions: The pharmacokinetic characteristics of fluralaner explain its prolonged activity against fleas and ticks on both dogs and cats after a single topical administration.

 

Keywords: Fluralaner, Dog, Cat, Pharmacokinetics, Bravecto™ Spot-on Solution

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EFFICACY OF FLURALANER FLAVORED CHEWS (BRAVECTO®) ADMINISTERED TO DOGS AGAINST THE ADULT CAT FLEA, CTENOCEPHALIDES FELIS FELIS AND EGG PRODUCTION

Michael W Dryden, Vicki Smith, Tashina Bennett, Lisa Math, James Kallman, Kathleen Heaney and Fangshi Sun

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Abstract

Background: Fluralaner is a potent insecticide and acaricide with rapid and persistent efficacy. This study measured the efficacy of fluralaner flavored chews (Bravecto®, Merck Animal Health) administered to dogs against adult Ctenocephalides felis felis and egg production.

Methods: Twelve purpose-bred dogs were randomly allocated to two groups of six dogs each. Dogs in treatment group 1 were administered a single fluralaner flavored chew to achieve a minimum dose of at least 25 mg/kg while treatment group 2 served as untreated controls. On Days -2, 28, 56, 84, 91, 98, 105, 112, and 120 post-treatment, each dog was infested with approximately 200 unfed cat fleas, C. felis felis (KS1 strain). Forty-eight hours after treatment and 48 h after each infestation, eggs were collected over a 3-h period, counted and viability determined. Dogs were combed to remove any remaining fleas.

Results: Treatment of dogs with oral fluralaner provided a 100 % reduction in flea counts 48 h after treatment and within 48 h of every post-treatment infestation through Day122. Egg production from fluralaner treated dogs was reduced by 99.9 % (two eggs from one dog) within 48 h after treatment and not a single egg (100 % efficacy) was thereafter collected from treated dogs. Adult flea counts and egg production from the fluralaner-treated dogs were significantly lower than for non-treated controls at all post-treatment evaluations (P < 0.001). The two eggs collected from the single treated dog 48 h after treatment did not produce any adult fleas. As no additional eggs were collected from treated dogs, no viability assessment was performed.

Conclusions: A single oral dose of fluralaner flavored chews provided 100 % efficacy against repeated flea infestations on dogs for 4 months. Fluralaner reduced egg production of activity reproducing female fleas by 99.9 % and then killed every single female flea before any eggs could be produced following each subsequent re-infestation for the entire 122-day evaluation period.

 

Keywords: Flea, Ctenocephalides felis felis, Cat flea, Dogs, Fluralaner, Egg production, Adulticide activity, Contro

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*BRAVECTO kills fleas and prevents flea infestation. Bravecto Chew and Bravecto Topical for Dogs kills ticks (black-legged tick, American dog tick, and brown dog tick) for 12 weeks and also kills lone star ticks for 8 weeks. Bravecto Topical for Cats kills ticks (black-legged tick) for 12 weeks and American dog ticks for 8 weeks.

IMPORTANT SAFETY INFORMATION:
BRAVECTO has not been shown to be effective for 12-weeks’ duration in puppies or kittens less than 6 months of age. Fluralaner is a member of the isoxazoline class. This class has been associated with neurologic adverse reactions including tremors, ataxia, and seizures. BRAVECTO Chew: The most commonly reported adverse reactions include vomiting, decreased appetite, diarrhea, lethargy, polydipsia, and flatulence. BRAVECTO is not effective against lone star ticks beyond 8 weeks of dosing. Seizures have been reported in dogs receiving isoxoline class drugs, even in dogs without a history of seizures. Use with caution in dogs with a history of seizures or neurologic disorders. BRAVECTO Topical Solution for Dogs: The most commonly reported adverse reactions include vomiting, hair loss, diarrhea, lethargy, decreased appetite, and moist dermatitis/rash. Bravecto is not effective against lone star ticks beyond 8 weeks of dosing. For topical use only. Avoid oral ingestion. Seizures have been reported in dogs receiving isoxoline class drugs, even in dogs without a history of seizures. Use caution in dogs with a history of seizures or neurologic disorders. BRAVECTO Topical Solution for Cats: The most commonly reported adverse reactions include vomiting, itching, diarrhea, hair loss, decreased appetite, lethargy, and scabs/ulcerated lesions. BRAVECTO is not effective against American dog ticks beyond 8 weeks of dosing. For topical use only. Avoid oral ingestion. The safety of BRAVECTO has not been established in breeding, pregnant and lactating cats. Neurologic adverse reactions have been reported in cats receiving isoxazoline class drugs, even in cats without a history of neurologic disorders. Use with caution in cats with a history of neurologic disorders.

References: 

1. Bravecto Chew for Dogs [prescribing information]. Madison, NJ: Merck Animal Health; 2014. 
2. Bravecto Topical Solution for Dogs [prescribing information]. Madison, NJ: Merck Animal Health; 2016. 
3. Bravecto Topical Solution for Cats [prescribing information]. Madison, NJ: Merck Animal Health; 2016. 
4. Rohdich N, Roepke RKA, Zschiesche E. A randomized, blinded, controlled and multi-centered field study comparing the efficacy and safety of Bravecto™ (fluralaner) against Frontline™ (fipronil) in flea- and tick-infested dogs. Parasites & Vectors. 2014;7:83. 
5. Beck S, Schein E, Baldermann C, von Samson-Himmelstjerna G, Kohn B. Tick infestation and tick prophylaxis in dogs in the area of Berlin/Brandenburg – results of a questionnaire study. Berl Munch Tierarztl Wochenschr. 2013;126(1-2):69-76. 
6. Kidd L, Breitschwerdt EB. Transmission times and prevention of tick-borne diseases in dogs. Compend Contin Educ Pract Vet. 2003;(25)10:742-751. 
7. Freedom of Information Summary, NADA 141-426. Approved May 15, 2014. 
8. Freedom of Information Summary, NADA 141-459. Approved 2016. 
9. Gassel M, Wolf C, Noack S, Williams H, Ilg T. The novel isoxazoline ectoparasiticide fluralaner: selective inhibition of arthropod γ-aminobutyric acid- and L-glutamate-gated chloride channels and insecticidal/acaricidal activity. Insect Biochem Mol Biol. 2014;45:111-124. 
10. Williams H, Demeler J, Taenzler J, Roepke RK, Zshiesche E, Heckeroth AR. 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. Parasites & Vectors. 2015;8:352. 
11. Taenzler J, Wengenmayer C, Williams H, et al. Onset of activity of fluralaner (Bravecto™) against Ctenocephalides felis on dogs. Parasites & Vectors. 2014;7:567. 
12. Meadows C, Guerino F, Sun F. A randomized, blinded, controlled USA field study to assess the use of fluralaner tablets in controlling flea infestations. Parasites & Vectors. 2014;7:375. 
13. CAPCvet.org. Accessed July 5, 2016. 
14. Data on File, Merck Animal Health. 
15. Taenzler J, Liebenberg J, Roepke RKA, Heckeroth AR. Prevention of transmission of Babesia canis by Dermacentor reticulatus ticks to dogs treated orally with fluralaner chewable tablets (Bravecto™). Parasites & Vectors. 2015;8:305. 
16. Wengenmayer C, Williams H, Zschiesche E, et al. The speed of kill of fluralaner (Bravecto™) against lxodes ricinus ticks on dogs. Parasites & Vectors. 2014;7:525. 
17. Walther FM, Allan MJ, Roepke RKA, Nuernberger MC. Safety of fluralaner chewable tablets (Bravecto™), a novel systemic antiparasitic drug, in dogs after oral administration. Parasites & Vectors. 2014;7:87. 
18. Walther FM, Allan MJ, Roepke RKA, Nuernberger MC. Safety of fluralaner, a novel systemic antiparasitic drug, in MDR1(-/-) collies after oral administration. Parasites & Vectors. 2014;7:86. 
19. Burgio et al. Parasites & Vectors (2016) 9:626. 
20. Meadows et al, Parasites & Vectors, (2017) 10:36. 
21. Meadows et al, Parasites & Vectors, (2017) 10:37.